Volume 21, Issue 4

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F. Ganong,. Univ. of California,. San Francisco. Council ... Cell Physiology. American. Journal of Physiology: ... The Physiology. Teacher. THE PHYSIOLOGIST.











of promoting






its utilization.

for Physiologists and Physiology Orr E. Reynolds, Editor

OFFICERS President David

F. Bohr,


of Michigan,




President-Elect Ernst



of Pittsburgh

Past President William

F. Ganong,


of California,

F. Bohr,



Executive Orr



C. Randall,

William Earl

F. Ganong,

H. Wood,




C. Johnson


. . . . . . . . . . . . . . . . . . . . . . . (continued)

of Papers


. . . . . . . . . . . . . . . . . . 134

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*An asterisk following Abstracts are arranged


Publications American





of Physiology: of



01 WY American


Comparative American




Physiology of Physiology: of











of Physiology:

Physiology American Journal of

and Journal






of Physiology










Exercise Physiology of Neurophysiology

Physiological Reviews The Physiologist Handbooks

of Physiology




is published




members institutions, $12.50;






Physiological ments and

Distributed as a part of $12.00






XXVIII IUPS Congress I UPS Registration Card

. . . . . . . . . . . . . . . . . . . . . . 141


E. Reynolds,





CAS Brief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Hypoxia Symposium 1979 . . . . . . . . . . . . . . . . . . . 138






San Francisco




per and

Society opinions


assumes advanced



Pike, to this


Bethesda, address.

with The Physiology Teacher membership. Non-members

year Postal









no responsibility by contributors

to and

Canada, American

for the stateto THE PHYSI-

an author’s in alphabetical

name order

denotes “by by first-named

invitation.” author.


ELECTRON MICROSCOPIC EVIDENCE FOR FIBER FOLDING AND THE SLIDING FILAMENT MODEL OF CONTRACTION IN A SMOOTH MUSCLE Robert K. Abercrombie and Roland M. Bagby. Department of Zoology, University of Tennessee, Knoxville, TN 37916 The ventral proboscis retractor muscle (VPRM) of p. gouldi exhibits a bimodal length-tension curve. Previous work has established that fiber folding of large myosin containing fibers (LMF) is involved with the first peak (1.0 Lo) of the length-tension curve and no folding is involved with the second peak (1.67 Lo) (Abercrombie and Bagby, Fed. Proc. 37: The existence of two cell types (LMF and sma= 785, 1978). straight paramyosin containing fibers (SPF)) raised many questions as to the mechanism of contraction. After determining the length-tension relationship, VPRM were fixed for EM at 0.5,1.0,1.67,1.88,2.00, & 2.14 Lo. Examination of longitudinal sections revealed that at 0.5 Lo the LMF were folded and the myofilaments appeared to bend. However the SPF and their myofilaments were straight. At 1.0 Lo the LMF were folded but the myofilaments were straight even at the fold angle of the fiber. The SPF were also straight. From 1.3-2.14 Lo both LMF and SPF were straight. These results support the hypothesis that the LMF are folding due to the SPF. Examination of cross sections revealed a homogeneous array of thick and thin filaments from 0.15-1.3 Lo. From 1.32.14 Lo, areas of only thin filaments or only thick filaments or areas of thick and thin filaments could be observed. These observations are consistent with a sliding filament model of contraction. (Supported by NIH Grant HL18077-03).

THE EFFECTS OF SPACE FLIGH'l' ON SOME LIVER ENZYMES CONCERNED WITH CARBOHYDRATE AND LIPID METABOLISM IN RATS. S. Abraham*, C. Y. Link, H. P. Klein+ and C. Volkmannt. *Bruce Lyon Mem. Res. Lab,, Children's Hospital Med. Ctr., Oakland, CA. and +Ames Res. Ctr., NASA, Moffett Field, CA. The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats exposed to prolonged space flight (18.5 days) aboard COSMOS 936 Biosatellite. When flight stationary (FS) and flight centri-, fuged (FC) rats were compared at recovery (Ro), decreases in the activities of glycogen phosphorylase, a-glycerolphosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase were noted in the weightless The significance of these findings was strengthgroup (FS). ened since all activities, showing alterations at Ro, returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at RO contained, on the average, more than twice the amount of glycogen than did controls and a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear Our data justify to be unique to the weightless condition. the conclusion that centrifugation during space flight is equivalent to terrestrial gravity. (Supported by NASA Contract No. NAS2-9523).

MODEL OF HYPOGLYCEMIA FOLLOWING REMOVAL OF PHEOCHROMOCYTOMA. E. Ackerman, L. C. Gatewood*, Health Computer Sciences, University of Minnesota, Minneapolis, MN 55455 and C. Reynolds*, G. E. Wilkins*, N. Schmidt*, and W. Doll*, St. Paul's Hospital, Vancouver V6Z lY6, B.C., Canada By monitoring free C-peptide immunoreactivity (F-CPR), it has been shown that insulin release is inhibited by the excess catecholamines which are produced by pheochromocytoma. Following tumor removal, blood glucose drops over several hours reaching hypoglycemic levels if iv glucose is not given. F-CPR levels indicate that insulin is re1eased.l Simulation of a mathematical model, an extension of one published recently,2 was undertaken to determine if a normal insulin response to the release from inhibition by catecholamines could, in itself, account for the apparently excessive drop in glucose. When model parameters were set in the middle of the normal range, in spite of starting with high glucose levels and negligible insulin levels, the simulated glucose fell smoothly approaching normal levels in several hours. However, if insulin antibodies are included in the model, or if certain sets of parameters still within the normal range are selected, the simulated blood glucose falls to hypoglycemic levels before returning to normal. These results indicate that the large insulin response following removal of a pheochromocytoma could account for later hypoglycemia. 1. C. Reynolds, Endocrine Society Meeting, 1978. --et al. 2. R. Celeste, et al. Bull Math Biol 40:59-77, 1978.

IN VITRO STUDIES OF SOME NEW ANTISICKLING AGENTS. Adhikary* and J.K. Haynes* (Spon. M.R. Banerjee) of Genetics and Molecular Medicine, Meharry Medical Nashville, Tennessee 37208

2-{benzoylamino} pyridinium benzoate (BAPB) has been reported to exert an antisickling effect in --in vitro studies with S/S erythrocytes. Two new compounds: 2{benzoylamino) pyrimidinium benzoate (BAPMB) and 2-(benzoylamino) thiazolium benzoate (BATB), which are structurally similar to BAPB have since been synthesized and their antisickling effects have been compared with that of BAPB. At a drug concentration of 10m2M, BAPMB and BATB inhibited sickling by 95% and 67%, respectively, while BAPB inhibits sickling by 87%. BAPMB- and BATB-treated hemoglobin S is inhibited from gelling like BAPB-treated hemoglobin S. Cellulose acetate electrophoresis of BAPB-, BAPMB- and BATBtreated hemoglobin S did not reveal any alteration in charge or size as found in the electrophoresis of adipimidate-treated hemoglobin S. These results suggest that BAPMB and BATB prevent sickling by inhibition of gelation of hemoglobin S similarly to the mechanism previously proposed to explain the antisickling activity of BAPB.

ELECTROPHYSIOLOGY OF K SECRETION IN FRESHWATER PRAWN MIDGUT. G.A.Ahearn. Dept. Zoology, Univ. Hawaii, Honolulu, Hi. 96822 Transmural electrical potential difference (PD) across in vitro, perfused midgut of freshwater prawns (Macrobrachium rosenbergii) bathed on both surfaces with saline approximating normal hemolymph composition was - 1.63 2 0.26 mV (mean 2 1 SEM; n = 6; mucosa negative). Simultaneous mucosal and serosal alterations of [K] from 1.0 to 8.1 mM resulted in a hyperbolic increase in PD. A plot of PD vs. PD/[K]m+s provided the following transport constants: Kt = 10.7 + 1.2 mM K; > 8.1 mM transmural PD pDmax = 3.85 t 0.34 mV. At [K]bs approached zero, suggesting an inhibitory effect of excessive K on electrical activity. Complete replacement of K by Na (m + s) resulted in a transient luminal positive potential (+ 1.12 2 0.29 mV; n = 5) followed by a gradual drop to zero PD, suggesting diffusional flow of K from epithelium to lumen. Addition of 1 mM NaN3 + 1 mM iodoacetate to normal saline on both gut surfaces or 0.5 mM ouabain to the serosa eliminated luminal negativity (zero PD). Unidirectional transmural 42K fluxes from serosa to mucosa exceeded those in the opposite direction (Jim = 1.10 ? 0.07, n = 5; J& = 0.63 ? 0.08, n = 8 pmoles cm- 2 hr-1), indicating a significant net secretion of this cation into the lumen. Replacement of Na by choline (m + s) eliminated K secretion (JK = 0.41 ? 0.06, n = 5; JK = 0.39 + 0.03, n = 4 umoles cm'? hr-1). An electrogenicm?Na/lK exchange transport model will be discussed relating K secretion to previously determined Na, Cl and water absorption in this tissue. (Supported by NSF grant PCM 76-84105).

ADRENOCORTICAL HYPOFUNCTION AFTER METYRAPONE IN DEVELOPING RATS. S. Fong Akana* and P. S. Timiras. Dept. PhysiologyAnatomy, Univ. of California, Berkeley, Ca. 94720. Drug inhibitors of plasma glucocorticoids are used clinically to test hypothalamo-pituitary-adrenal competence. Metyrapone, an ll-beta-hydroxylase inhibitor, blocks the final step in the synthesis of corticosterone. Because its effectiveness in the young is sti?l unknown, we have investigated the lowest dose of metyrapone that will maximally reduce plasma corticosterone at a age critical for growth and endocrine maturation. In a first experiment, we administered a single S.C. injection in graded doses (75-300 mg/kg b.w.) to LongEvans 12-day-old rats and measured the plasma corticosterone the maximal suppression was levels after 1,2,3 and 4 hrs; 39%, less than the 70% reported for comparable doses in adult rats. For all doses, maximal suppression occurred 3 hrs after injection. In a second series of experiments, metyrapone was injected repeatedly during 48 hrs: a dose of 150 mg/kg b.w. injected every 4 hrs was not compatible with survival, but 100 mg/kg&.w. administered at 6 hr intervals was capable of maximally reducing plasma corticosterone levels without morThe degree of suppression (45%) was similar to that tality. obtained with the highest single dose. These results suggest that metyrapone can suppress plasma corticosterone levels in the young animal but that its effectiveness is limited by the animal's survival. (Aided by the UCB Biomedical Science Funds and the Graduate Minority Program.)

P.K. Dmsion College,

PULMONARY FUNCTION CHANGES IN HYPEROXIC TREATED GUINEA PIGS. T. K. Akers and D. Whitley*. Dept. Physiology, Univ. of North Dakota, Grand Forks, ND 58202. In anesthetized guinea pigs airflow, tidal volume, and compliance decreased and respiratory rate and airway resistance increased after 6 days exposure to 500 mm Hg 02 diluted to 1 atmosphere absolute (ATA) with He and also 500 mm Hg 02 in 20 ATA He. Pretreatment with a depleting dose of reserpine for 10 days significantly increased the compliance and decreased the aiway resistance in the 1 ATA He-02 animals. Alphablockade with phenoxybenzamine caused a significant increase in tracheal airflow in both 1 ATA He-02 and 20 ATA He-02. All treatments were compared to 1 ATA air control. Scanning electron micrographs of the lungs indicated some protection by the drugs at the alveolar level. The results indicate that sympathetic active drugs alter the pulmonary function in ways that involve the micro-vasculature of the lung. (Supported in part by ONR Contract No. N00014-76-C-0219 and NIH Training Grant No. 5 TO1 HL05939.)

MYOTHERMAL VS. ENZYMATIC CHANGES IN THYROTOXIC CARDIAC N.R. Alpert, R.Z. Litten* and L.A. Mulieri. HYPERTROPHY. Dept. of Physiology G Biophysics, Univ. of Vermont, Burlington, Vermont 05401 Myothermal measurements were made on isolated right vengricular papillary muscles using a Hill type thermopile at 21 C. Calciumand actin-activated ATPase was measured on myosin isolated from the right ventricular free wall of the same hearts . Experiments were carried out on eight rabbits following 14 daily intramuscular injections of 0.2 mg/Kg of LBlood T4 was 136% above controls thyroxine (T4) in saline. at sacrifice. Right ventricular free wall to body weight ratio increased 70% above controls. Isometric twitch tension (0.2 Hz), maximum tension rate, contraction time, and relaxation time were changed (pc.001) to 61%, 108% (n.s.), 53%, and 66% of normal, respectively. Tension dependent heat per unit twitch tension was 225% of normal (pc.001) while calciumand actin-activated myosin ATPase was 240% (pc.001) and 174% of normal (p

Gd (L/cm

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Gd were greater at TLC and 18356 from NHLI).


IN VIVO CONDUCTION OF NERVE SPIKES IN REGENERATING GIANT F I BERS OF EARTHWORMS. R. J. Baiter*, J. L. McFall* and C. D. D rewes . Department of Zoology, Iowa State University, Ames, Iowa 50011. Ventral nerve cords of the earthworm. Lumbricus terrestris. were transected posterior to the clitellum. Spikes of the I regenerating medlal (MGF) and lateral (LGF) giant fibers were recorded through the skin of intact freely moving animals. First indications of spike coupling across the lesion were seen as early as six days for the MGF and eleven days for the LGF. At these times coupling was not one-to-one. That is, trains of several MGF spikes initiated by tactile stimulation of the head were conducted posteriorly up to the lesion but gave rise to only single spikes posterior to the lesion. initiated posteriorly by elecSimilarly several MGF spikes, trical stimulation, were conducted anteriorly toward the lesion but gave rise to only single MGF spikes anterior to Later stages of functional recovery were the lesion. characterized by an increased tendency for one-to-one Patterns of coupling of MGF spikes across the lesion. coupling in the regenerating LGF were similar to those of the MGF.

MITOCHONDRIAL ALTERATIONS IN THE Rave TUMOR. G.S. Bambec,k*, R.T. Heath and R.M. GesFnski*. Dept. of Biological Sciences, Kent State University, Kent, OH 44242. Mitochondria isolated from the Rave mouse tumor differ structurally and functionally from mitochondria isolated from other tissues of tumorous and non-tumorous DBA/lJ mice. The Rave tumor is a lymphoblastic lymphoma which has been transplanted serially for over 400 generations subcutaneously, and has maintained a stable morphology. Mitochondria were isolated by differential centrifugation from liver, kidney, heart and striated muscle of non-tumorous mice and from'the liver and tumor of tumorous mice. Oxygen consumption of isolated mitochondria was measured polarographically in the presence of excess succinate and ADP (expressed as umole 02 consumed/min/mg. protein). Tumor mitochondria consumed oxygen about 5-10 times slower than mitochondria from all other tissues tested. Major polypeptide composition of whole mitochondria was determined by SDS-polyacrylamide gel electrophoresis: 15 ug. protein/gel; 8mA/gel. Tumor mitochondria contained a unique peptide of 19,000 daltons, and they lacked peptides of 31,500 daltons and 88,000 daltons, two components found in mitochondria isolated from all other tissues studied.

INCREASED PHRENIC ACTIVITY COMPENSATING FOR DECREASED DIAPHRAGM LENGTH PERSISTS AFTER C7 SPINAL SECTION. R.B. Banzett,* G.I. Inbar,* E.N. Bruce,* and J. Mead. Dept. of Physiology, Harvard School of Public Health, Boston, MA 02115. Awake man and monkey increase electrical activation of the diaphragm when its resting length is reduced by positive pressure breathing. The anesthetized rabbit responds similarly after vagotomy (Bruce 1977). This increased dia-et al A' phragm activation often occurs in the first breath after the stimulus is applied and occurs in the absence of end-tidal suggesting that the response is a reflex origiPC02 changes, nating in receptors of the rib cage or diaphragm. To investigate further the afferent pathway of this response we have examined anesthetized rabbits after sectioning the spinal cord both vagi, eliminating afferent at C7, and cutting pathways from both lungs and rib cage. To test the response-we applied positive pressure at the airway opening and introduced pneumothorax, thus reducing the length of the diaphragm without changing lung volume. This maneuver increased phrenic amplitude in 5 rabbits, 4 of which continued to respond after C7 section, and 3 after both C7 section and vagotomy. In contrast to our earlier work, a number of rabbits never responded to positive pressure, presumably due to the trauma of spinal surgery. Thus we conclude that the only afferent pathway likely to mediate the reflex is the phrenic nerve, which carries muscle receptor information from the diaphragm. (Supported by grant HL 05014-02 and HL 14580).

OPTIMAL TEMPERATURE CONTROL IN TWO COMPARTMENT ENDOTHERMS. B.J. Barber. Dept. of Physiology and Biophysics, Univ. of Miss. Med. Ctr., Jackson, MS 39216. It is unlikely that homeothermy first appeared in its An optimal primitive thermoregulator present complex form. is sought in the sense that core temperature (Tc) variation Given a two is minimized with a minimum gain requirement. compartment (core-shell) animal with temperature sensors in both compartments, metabolic heat production (M) in the core (C) and evaporative heat loss (E) from the shell (S) four independent control combinations are possible: CM/CE, CM/SE, SM/CE and SM/SE where S, C indicate sensor location and M,E indicate the effector variable. Solutions are derived for Linear comcontinuously proportional and threshold systems. to variable set-point binations of these solutions correspond hypotheses. The steady state solution for the cross-coupled existing experiSM/CE controller shows best agreement with mental data: (1) T, is independent of ambient temperature, (2) shell temperatu:e is invariant during exerci se, and (3) shivering and sweating can occur at the same T,. Furthermore, the SM/CE controller requires minimum sensitivity to minimize variations in T,. If homeothermy has survival value then it would appear that a primitive low gain SM/CE animal would have been the most likely to survive.

CHANGES IN BLOOD FLOW AND ST-SEGMENT DURING CORONARY OCCLUSION IN DENERVATED AND NON-DENERVATED CANINE HEARTS. M.J. Barber*, J.X. Thomas, Jr., D.E. Euler and W.C. Randall. Dept. Physiol. Loyola Univ. of Chicago, Stritch Sch. Med., Maywood, 11.60153. Recent evidence shows chronic surgical denervation (DNV) provides protection to the heart during ischemia. In this study, two groups of 4 dogs each, sham-DNV and intrapericardial DNV, were prepared and allowed to recover. Two weeks post-op all dogs were anesthetized with pentobarbital and blood pressure (BP), contractile force (CF) and heart rate (HR) monitored during stimulations of the left and right stellate ganglia and cervical vagi. No change in HR or CF with nerve stimulation confirmed DNV. Myocardial blood flow (BF) was measured with radiolabeled microspheres (15+3~) before and during LAD occlusion (OCC) in both groups. DNV dogs showed significant reduction in control left ventricular BF (118.0? 10.8 vs 77.2210.9 ml/min; p< .Ol) before OCC. Recording from 7 transmurally paired epicardial and endocardial electrodes during OCC showed DNV dogs exhibiting fewer sites with ST elevation greater than 2 mv. The ischemic region of the DNV heart showed a mean flow reduction of 24% compared to 55% in similar regions of the sham. Where DNV and sham animals showed areas of similar BF at 15 min. of OCC, there was significantly less ST elevation in the DNV animal. These results suggest the DNV heart develops less ischemic damage at a similar level of flow than does the non-DNV heart. This may be mediated by a reduced energy demand in the DNV heart. (Supported by NIH Grant HL 08682).

INTRINSIC AND EXTRINSIC PROBES OF ISCHEMIC BORDER ZONE IN CRYSTALLOID AND BLOOD PERFUSED RABBIT HEARTS. C.H. Barlow*, B. Chance, W.R. Harden*, H. Rastegar*, M.B. SimpsonX and A.H. Harken. Johnson Research Foundation and Harrison Department of Surgical Research, University of Pennsylvania, Philadelphia, PA 19104. USA Sensitive techniques to measure the spectral properties of intracellular chromophores now permit the two and three dimensional assay of tissue bioenergetics. Ischemia was produced by a coronary artery ligation in isolated rabbit hearts perfused using a single pass crystalloid system or blood recirculated through a support rabbit. Epicardial NADH fluorophotography demonstrated high NADH concentration in ischemic zones which are boundaries at the ischemic-normoxic interface in both systems. Fluorescein angiography delineated the perfused capillary to critical tissue pO2 distance to be 250 u in crystalloid perfused, freeze-clamped heart. The tissue oxygen gradient at the ischemic border appears to be 2- 3 torr/p in crystalloid perfused hearts. The width of the i schemic border appears to be 250 p or less in both blood or crystalloid perfused hearts. (Supported by USPHS grants HL-22315 and HL-18708)




K.W. Barron* and V.S. Bishop. The Univ. of Texas Health Sci. Center, San Antonio, Texas 78284. Afferent vagal fibers from the cardiopulmonary region have been reported to inhibit sympathetic efferent activity. Reports from this lab have demonstrated that bilateral vagal cold block (BVB) in the conscious dog increases mean arterial pressure (MAP) independent of increases in heart rate (HR). The purpose of this study was to examine the relative roles of the right versus left vagi in mediating cardiopulmonary inhibitory reflexes in the conscious dog. BVB in 10 dogs increased MAP 24+28 mmHg and HR 63+9.5. Right vagal cold block (RVB) and left-vagal cold block TLVB) increased MAP 61% and 15% respectively) and HR (66% and 14% respectively). BVB increased MAP >RVB which was >LVB. The relative differences in MAP due to LVB, RVB and BVB were independent of HR since similar increases in MAP were observed after atropine. Intracoronary (IC) injections of veratridine (ver) 0.1 Ng/kg (6 dogs) decreased MAP and HR 39 mmHg and 28 b/m respectively. LVB and RVB decreased the reflex HR response to ver (-50%). The reflex hypotension due to IC ver was attenuated 50% by RVB but unaffected by LVB. In the dog tonic vagal inhibition of the vasomotor center appears to be predominantly in the right vagal afferent nerves. Furthermore, the dominate afferent pathway for the Bezold-Jarish also appears to be in the right vagus. (Supported by NIH Grant HL-12415)

CARDIAC CELLULAR INTEGRITY AFTER REPERFUSION IN CATS GIVEN Thomas DEXAMETHASONE. R.J. Barsotti and J.A. Spath, Jr. Jefferson University, Philadelphia, PA 19107. Anesthetized cats were subjected to five hours of sham operation (n=lO) or circumflex artery ligation for two hours followed by reperfusion for three hours. Prior to coronary artery ligation, cats were given dexamethasone sodium phosphate, DSP (8 mg/kg, iv, n=6) or its vehicle (n=7). Shamoperated cats were given DSP. After five hours, samples of cardiac tissue were taken to determine creatine kinase (CK) activity and for light and electron microscopy. Radioactive microspheres were used to determine regional myocardial blood flow in 3 to 5 cats in each group. In sham-operated cats given DSP, CK activity was 8.220.5 IU/mg dry tissue (mean?SE) in subendocardial tissue of the posterior ventricular wall. After reperfusion, cardiac CK was 33 to 40% less in cats given vehicle or DSP (~~0.01 sham vs. reperfusion). Mitochondrial swelling and cellular disruption was evident in these hearts. Moreover, staining of reperfused hearts using hematoxylin-basic fuchsin-picric acid indicated ischemic injury in treated and untreated hearts. In addition, subendocardial blood flow to the posterior ventricular wall was 57 to 76% less than that of sham-operated cats (~~0.01) in cats given DSP or its vehicle prior to ligation. These results indicate significant cellular damage after reperfusion of ischemic myocardial tissue and suggest that dexamethasone is unable to maintain myocardial cellular integrity during reperfusion of severely ischemic tissue. (Supported by grant #HL-20283-02 from NHLBI.)

EFFECT OF ANESTHETICS ON TRACHEAL OCCLUSION RESPONSE. H.L. BATSEL, J.R.R. BOBB, AND B. ROOT*. VA HOSPITAL, LONG BEACH, CA 90822. Effects of a variety of anesthetics on the control of breathing were studied by subjecting unanesthetized, decerebrate cats to stepwise increases of anesthetic. Halothane, enflurane, pentobarbital sodium and ketamine were studied, each in groups of 5 animals. The inspiratory response to tracheal occlusion (applied during end expiration) served as an indicator of respiratory center output. In the unanesthetized decerebrate cat breathing O2 alone, the tracheal occlusion response reached mean peak pressure of -12 cm H20 (PTo) and was self-terminating at inspiratory duration (TIo) of twice spontaneous inspiration. Halothane caused progressive diminution of PTo with slight diminution of TI . Pronounced at 3% to 5% inspire 8 halothane. depression of PTo occurred at inspired concentrations of 3% to 5X, caused Enflurane, modest depression of P but there was obvious lengthening by halothane and enfluof TIO in all cases. do anges produced rane were rapidly restored to near control values when the preparations were returned to breathing 100% 0 . Both ketamine z n PTo, but at and pentobarbital caused little if any change eventually became infinite, i.e. inspirasome dose level TI ? tion became apneus ic in character.

CYTOPLASMIC ESTROGEN RECEPTOR REPLENISHMENT. Lawrence J. Baudendistel*, Mary F. Ruh, Eli M. Nadel*, and Thomas S. Rub. Dept. of Physiology, St. Louis Univ. Sch. of Med., St. Louis, MO 63104 The effect of the e-in vivo administration of various tr;iphenylethylene antiestrogens and physiological (0.05 ug) versus pharmacological (0.5-5 ug) doses of estradiol-17B (E2) on the uterotrophic process in general and the nuclear accumulation and cytoplasmic depletion and replenishment of uterine estrogen receptor was determined. Regardless of the dose of E2 the changes in uterine wet weight, total protein and incorporation of 3H-thymidine into DNA and 14C-leucine into protein were the same at 24 h. The antiestrogens (100 ug) were as equally effective as E2 (5 ug) in stimulating uterine growth at 24 h, indicating that antiestrogens did not antagonize general macromolecular synthesis. The effect of E2 or antiestrogens (100 ug) on the replenishment of the cytoplasmic estrogen receptor was also studied. The net increase, above control, of cytoplasmic estrogen receptor at 24 h and 48 h after E2 injection was approximately 0.35 and 0.77 pmoles/ uterus respectively. The effect of antiestrogens (U-ll,lOOA, CT-628, en- and zuclomiphene) on the increase in cytoplasmic estrogen receptor at 24 h and 48 h measured from maximally depleted levels was nearly identical to the E7 induced net increase. This suggests that in both cases &ese particular increases represent newly synthesized receptor and that E2 causes some receptor replenishment a recycling through process.

A HYPOTHESIS ON THE MECHANISM OF SECRETORY DIARRHEA. Paula T. Beall and Rick T. Calvin*. Departments of Pediatrics and Physiology, Baylor College of Medicine, Houston, TX 77030. The loss of large amounts of isotonic fluids into the lumen of the small intestine is a common symptom of secretory diarrheas, such as cholera. Ling proposed in 1965 that the llsecretory diarrheas" could be caused by a loss of structure in the bulk phase cytoplasmic water of the intestinal enterocyte. More snecifically, we propose that the actin filaments of the brush border and terminal web of the enterocyte are the nrimary proteins regulating the water-protein resistance to water and ion flow across the intestinal lining. Alterations of the conformational state of actin filaments in this region of the enterocyte were predicted to produce diarrhea1 symptoms. Thirty cm of small intestine of male rats were double tied into six closed loons and 0.5 cc of solutions of cholera toxin (10 pg/ml), saline, heat inactivated cholera toxin, 0.1% DMSO, and Cytochalasin B (lo-100 &ml) in 0.1% DEilSO were in,jected into each loop. After 5 hrs, both the cholera toxin loop and the Cytochalasin B loop showed increased luminal fluid of similar amounts, while the controls did not. It is possible that Cytochalasin B, which is known to depolymerize linear actin filaments into a globular protein form, may produce diarrhea1 symptoms by disrupting water-protein interactions in the terminal web of the enterocytes. (Supnorted by ONR Contract ~00014-76, NIH grants GM-20154 and ~-21624, and The Robert A. Welch Foundation Q-390.)

PRESSURE RELATED CHANGES IN HEART RATE AND THEIR RELATION TO THE HPNS IN THE MOUSE. R. W. Beaver, R. W. Brauer, and W. Mansfield". Institute of Marine Biomedical Research, UNCWilmington, 7205 Wrightsville Ave., Wilmington, N. C. 28403. In heliox breathing, as in liquid breathing, mice increases in pressure are associated with a progressive decrease in heart rate which reaches approximately 40% at 140 atm. This decrease is not affected by atropine. It is shifted to substantially higher pressures in the presence of phenobarbital. Type I HPNS convulsions occur when heart rates have just begun to drop; they are not accompanied by any recognizable seizurerelated changes in heart rate. Type II convulsions occur at a pressure where heart r&es have dropped approximately 20%. They are associated with a profound transient drop in heart rate which is coextensive in time with the actual seizure episode, may reach 80% or more depression and can be blocked by at ropine. The same Type II seizure associated decrease in heart rate is observed in phenobarbital pretreated mice even though here Type II seizures occur at pressures as high as 200 atm. Interaction of these phenomena with other drugs, and the probable implications of the results will be discussed. (Supported jointly by ONR and the Naval Research and ~00~14-75-C-0468.) Development Command - ONR Res. Contr.

INFLUENCE OF AGE, SEX, TRAINING AND PREGNANCY ON THE OXYGEN CONSUMPTION OF RATS. T.G. Bedford,* N.C. Wilson,*, C.M. Tipton, R.A. Opplinqer,* and C.V. Gisolfi. Exercise and Stress Physiology Laboratories, U. of Iowa, Iowa City, IA 52242. -The c%truction of an enclosed treadmill and the standardization (r=.97; N=17) of a multistage exercise test (Med. Sci. Sports l&58, 1978) provides an effective method to evaluate training mechanisms in a variety of experimental conditions. The test was used with 46 male and 30 female hypertensive rats (SHR) who were between 45-60 days old. Their means and SD were 86.7k9.0 and 89.2k7.08 ml/kg*min-l, respectively. The animals were assigned to nontrained (NT) and trained (T) groups and selected results (-i(-, SD; + = < .05) were: Group







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54.42 4.9 76.0+15.8+ and

ONR N0015-75-C0597.

DISTAL TUBULE-GLOMERULAR FEEDBACK RESPONSES DURING NEPHRON PERFUSION WITH AN ISOTONIC MANNITOL SOLUTION IN THE RAT. P.D. Be1 1 $T, J.G. Rudulph::, C.E. Thomas+, D.W. Ploth, and L.G. Navar. University of Alabama Medical Center, Birmingham, AL 35294. Microperfusion studies in dogs have indicated that increases in perfusion rate (PR) result in decreases in stop-flow pressure (SFP) when mannitol, a non-electrolyte perfusate was used Previous studies in rats have failed to detect changes in SFP or single nephron glomerular filtration rate (SNGFR) suggesting a species difference. The present study was conducted to reassess the effect of mannitol on feedback responses in the rat. SFP or SNGFR was measured from an early tubule segment and the intermediate segment was blocked with wax. The later segment was perfused at 10 nl/min (LOW PR) or a,t 40 nl/min (HIGH PR), with artificial tubular fluid (ATF) or isotonic mannitol. In tubules perfused with ATF (N=13), control (no perfusion) SFP was 38+1.5 m m Hg (SE), decreasedto34+1.8 m m Hg at low PR and to 27+T.3 m m Hg at high PR. With mannrtol (N=22), control SFP was 33+.6 m m Hg, decreased to 29+2.2 m m Hg at low PR and to 31 +1.4 m m Hg at high PR. Control SKGFR (N=16) averaged 26+1.5 nl Tmin. With ATF (N=6), SNGFR was 23+3.4 nl/min at low PR-and decreased to 6+l.l nl/min at high PRT In mannitol perfused tubules (N=77, SNGFR was 23+4.7 nl/min at low PR, decreased to 9+2.5 nl/min at high PR. However, the degree of variabi 1 ity of tFe responses was greater in mannitol perfused tubules. These results indicate that mannitol can elicit feedback responses in the rat and raise the possibility that distal solute load or osmolality may influence the feedback mechanism.

PREVENTION OF DEATH FRO!4 ENDOTOXIN FOLLOWING EXTRACORPOREAL PERFUSION WITHOUT EXOGENOUS ANTICOAGULATION. B. K. Belier*, L. T. Archer*, R. T. Brantley*, and L. B. Hinshaw. V.A. Hosp. and Univ. Okla. Health Sci. Ctr., Okla. City, Okla. 73104. Our previous studies documented that canine blood could be circulated through an extracorporeal system without the utilization of exogenous anticoagulation. Further, data showed that the hemodynamic insult following endotoxin administration was lessened, and recovery from shock was suggested. The purpose of the present study was to determine the effect of this perfusion system on survival from endotoxin shock in anesthetized dogs. Blood was diverted from the distal aorta via plastic tubing at 50 ml/kg/min into a reservoir and returned by means of a roller-type pump to the femoral veins. Whole blood clotting times increased from a control of 7 min to greater than 18 hr within 45 min of perfusion in the absence of exogenous anticoagulation. After blood became incoagulable, animals were infused with 3 mg/kg E. coli endotoxin during a 30-min period. Systemic pressures-declined during the initial period but returned to baseline values, glucose remained at normal levels and all 6 dogs thus treated were healthy 7-day survivors. On the other hand, animals infused with endotoxin without extracorporeal perfusion demonstrated hypotension, hypoglycemia, and diarrhea, and 5 of 6 dogs died within 36 hr. (Supported by V.A. Hosp. and U.S. Navy Contract N00014-76-C0229 .)

TISSUE COMPETITION FOR AVAILABLE CARBOHYDRATES DURING HIBERNATION. H. W. Behrisch and M. Tallas*. Institute of Arctic Biology, University of Alaska, Fairbanks, AK 99701 A comparison of the hibernating Arctic Ground Squirrel (Citellus undulatus) with the non-hibernating one shows that -large alterations in the enzyme profiles occur in most - if not all - of the major tissues as the animal prepares for hibernation and during the hibernating state. These changes are accompanied by changes in isoenzyme composition and in the case of two regulatory enzymes studies - fructose 1,6Glybisphosphatase and pyruvate kinase - kinetic properties. colytic capacity rises in the hibernating state in cerebral cortex and mycocardium, only slightly in skeletal muscle; in This agrees with kidney cortex and liver it is decreased. continued nervous and cardiac function in hibernation. Similarly, pentose shunt activity is increased in cerebral cortex, myocardium and to a lesser extent in skeletal muscle, while in liver and kidney cortex it is markedly reduced during hibernation. On the basis of enzyme activities alone, it appears that gluconeogenic capacity is reduced in liver and kidney cortex during hibernation. However kinetics of the rate-limiting enzymes of gluconeogenesis (fructose bisphosphatase and phosphoenolpyruvate carboxykinase) are such that a decrease in temperature from 37 to 5OC results in an 8-22 fold decrease in SO.5 values for the substrates, thus potentiating an actual enhancement of gluconeogenic capacity at hibernating temperatures, and supporting previous work on gluconeogenesis in the whole hibernator. (Support from NIGMS 10402).

THE EFFECT OF CORONARY SINI& OCCLUSION ON CORONARY PRESSURE __ F'LOW RELATIONS. R. Bellamy: H. Lowensohn, W. Ehrlich, R. Biter* Walter Reed Army Institute of Research, Washington, DC 20012 and The Johns Hopkins Medical School, Baltimore, MD 21205 The immediate effect of transient coronary sinus occlusion on coronary pressure flow relations was studied in eight open chest dog preparations. The relation between aortic pressure and circumflex coronary blood flow was determined during diastoles prolonged by vagal stimulation at normal and elevated coronary venous pressure (P ), Two levels of flow were studiedt resting and at the peVak of the hy-peremia that followed a 15 second occlusion of the coronary artery, At peak flow, a linear relation was found between coronary flow and aortic pressure with flow stopping at a pressure (Pfzo) of 33 f lOnun Hg (x + ISD) when P was 5 &4mmHg. P increased to 9 & 11 mmHg when P was elzvated to 38 + limmff='bg y coronary sinus occlusion, C&onary flow fell promptly with slight elevation of The effect of coronary venous pressure elevation was to pV* translate the control pressure flow relation to a higher Ppo without altering the slope of the relation, With the peri-cardiurn open, Pfzo increased by about 6% of the increase in P. The data are consistent with the hypothesis that coronary b!food flow is controlled by a vascular waterfall mechanism in which Pv is one of the determinants of the surrounding pressure creating the waterfall effect. The mechanism by which P affects flow may be a direct mechanical increase in extravxscular compression associated with mechanical distension of intramyocardial veins.

EFFECTS OF L-NOREPINEPHRINE PERFUSED PROXIMAL TUBULE. Washington University of St. Louis, St. The sorption tubules

effect was


School of Louis, Missouri

Medicine 63110.

- The



of L-Norepinephrine (L-NE) on net water reabexamined in superficial proximal convoluted (PCT) isolated from rabbit kidney. The segments were perfused at 37’ with an artificial solution of the following composition (mM): NaCl 105, KC1 5, NaHC03 25, Na2HP0 4, Na acetate 10, MgSO 1, CaCl 1.8, glucose 8.3 and a ‘i anine 5, gassed with 95% b and 5%*CO (pH 7.4). The bath solution was identical ii compositi& to the perfusion solution except for the addition of 5% r bbit serum. The perfusion -7 rate averaged about 13 nl min . Epr PCTl the mean control value of J was 1.12 4 0.07 nl min m m . After the addition o! 4iNE l MeV), were, respectively, 3.64 x 105/cm2 (*ZO%), 9.5 x 105/cm2 (-30% to +50%), and 2.1 x 106/cm2. The total dose, as measured in TLD chips located at two sites in the US-25% part of the K 206 container, was 424 mrad (29%) and 523 mrad (211%). The mean tissue equivalent proton ender density, as measured in nuclear emulsions located in the US-25% part, was 2.72 x 105/cm 3=tissue. The physical parameters of the radiation environment reported here help specify important dosimetric information required to assess the potential radiation hazards to life systems in space.

Dept. of Medicine, Washington University, St. Louis, Missouri 63116 To facilitate characterization of myocardial metabolism and perfusion by residue detection of tracers, we developed a sanguinous, perfused isolated heart preparation with flow and substrate extraction maintained within the physiological range. Isovolumical ly beating rabbit hearts, paced at 180 beats/min were perfused retrograde at 60 m m Hg at 370 with non-recirculating Krebs-Henseleit buffer (KH) containing .4 mM albumin and .6mM fatty acid with or without washed sheep red blood cells (Hct = 25 or 40: KH - RBC25, KH - RBC40) with the perfusate filtered through a 13pm Swank filter to obviate microaggregation. LV systolic pressure averaged 63+4 (SE) m m Hg with KH (n = 7), 78+5 with with KH -RBC40 (n = 8). CorrespondKH - RBC25 (n = 28), and 97+6 ing values of peak dP/dt and LV pressure-time index averaged 663, 851, and 1232 m m Hg/sec, and 1705, 2149 and 2949 m m Hg/sec (p < .05 for al I differences). MV@ and fatty acid uptake increased linearly with increased left ventricular pressure (r = .88, .76, p and .57 for NO a-b1 (r=.76). Following a-b1 in hypoxic hypoxia, O2 was utilized more efficiently by skeletal muscle than by the body as a whole. (Supported by Grant HL 14693 from NHLBI)



THE EFFECTS OF SANGUINARINE UPON HUMAN RED BLOOD CELLS AND THIN LIPID MEMBRANES. P.M. Cala, J. Ndrby* and D.C. Tosteson Department of Physiology and Pharmacology, Duke University, Medical Center, Durham, North Carolina 27705. The plant alkaloid sanguinarine was found to inhibit Na-K In addition, transport by the pump in human red blood cells. it was observed that subsequent to pump inhibition the erythoIn order to help evaluate cytes became leaky to Na+ and K+. the nature of the sanguinarine induced leak, the alkaloid was added to the media bathing bilayer membranes formed from sheep red blood cell lipids. These studies showed that the concentration of sanguinarine which caused the Na and K fluxes across red blood cell membranes to increase by two orders of magnitude produced similar increases in bilayer conductance (Gm) at the limit of zero current and voltage. The sanguinarine induced conductance changes of bilayers were observed to exhibit a high power (- 4) dependence upon the medium sanguinarine concentration suggesting cooperativity bet\,reen sanguinarine molecules in the formation of the ion conducting pathway. While the red blood cell experiments showed that the charged form of the alkaloid was responsible for inhibition of the Na-K pump, experiments performed with bilayers demonstrated that it was the neutral form of sanguinarine which caused increases in Gm. Finally,the observation that the membrane current changes e fold for a 34 mV change in potential strongly suggests that sanguinarine forms voltage dependent (Supported by NIH Grant channels in lipid bilayer membranes. HL-12157 and NIH Postdoctoral Fellowship HL-01672.)

THE ROLE OF CATECHOLAMINES IN CENTRAL ANGIOTENSIN II-INDUCED RESPONSES Art Camacho*and M. Ian Phillips, Dept. of Physiol. University of Iowa, Iowa City, Iowa 52240 Angiotensin 11 (AII) injected intraventricularly (IVT) produces anincreasein blood pressure and drinking. The role of catecholamines in the mediation of these effects of AI1 was investigated. Male Sprague-Dawley with rats were prepared chronic IVT cannu lae and catheterized f emoral ar tery. Rats were tested to determine the effects of norepinephrine (NE) injected into the lateral (LV) and fourth ventricle, dopamine (DA) injected into the third ventricle both alone and preceeded by disulfiram (i.p.), a treatment to block the synthesis of NE, and AI1 preceeded by the alpha adrenergic blocker phentolamine (phe) given IVT. The results are summarized in the table below. IVT INJECTIONS MEAN BP mmHg A BP mmHg DRINKING ml AI1 (100 ng) 11.02 2.1 11.528.2 106.22 6.8 AI1 + phe(15 pg) 106.22 6.8 1.7 k 2.7 8.2 24.3 NE (1 pg) LV 103.02 3.3 9.7 * 6.8 0.0 NE (3 pg) IVth 105.3+9.0 17.72 8.6 0.0 DA (50 pg) 102.754.3 8.7 2 2.5. -20.12 3.5 0.0 DA + disulfiram -2.92 2.7 0.0 84.8 213.7 9.0 k4.9' DA at high concentrations exerts a pressor'effect followed b a depressor effect, dependent upon its conversion to NE. T Ke AI1 pressor response was blocked by an alpha antagonist but the drinking response was not. The results show that DA and NE alone do not produce thirst, but may be involved in the AI1 pressor response. Supported by NSF and NIMH RSDAII grants to M. I. P.

ROLE OF THE CATFISH KIDNEY IN ACID-BASE REGULATION. James N. Cameron. Depts. of Zoology & Marine Studies, Univ. of Texas, Port Aransas, TX 78373. Resting, post-operative channel catfish have variable rates of acid excretion by the kidney, and in some cases, a considerable net base excretion, mostly in the form of bicarbonate. Titratable acid and ammonia are generally small, except during post-operative acidosis. In response to respiratory acidosis (hypercapnia), there is a significant increase in the net H+ excretion by the kidney, mostly in the form of titratable acid, which has a pK resembling phosphate. Renal acid excretion returns to normal with a time course approximating the time course of compensation in blood pH, generally reaching control levels in less than 12 hrs. The renal component, on preliminary evidence, accounts for less than 10% of the total acid load excreted during the compensation phase. The balance is presumably excreted by the gills via ion exchange mechanisms (Na+ for NI-@ or H+). (Supported by grant PCM7724358 from NSF)

THE IMPACT OF CONSTANT LIGHT ON THE ESTROUS CYCLE OF THE RAT. C. S. Campbell and N. B. Schwartz, Dept. Biological Sciences, Northwestern University, Evanston, Ill. 60201. Prolonged exposure to constant light (LL) leads to anovulation and persistent estrus in the rat. The present work studPed the initial iqmct of LL on homns~ md Sehavioz-al cumponents of the rat estrous cycle. Albino rats were autopsied (N=S/group) at 1000 or 1700 on each day of the first 2 estrous cycles in either LL or LD14:lO (LD). In the first cycle, l/5 LL and 5/5 LD animals had surges of LH, FSH, and progesterone (P4) at 1700 proestrus. By 1000 estrus, l/5 LL animals and all LD animals had ovulated; by 1700 estrus, 3/5 LL animals had ovulated. The drop in serum estradiol (E2) levels was delayed, as were behavioral estrus and running activity onsets in all LL animals. In the second cycle in LL 2/5 animals at 1000 proestrus and l/5 at 1000 estrus had surges of LH, FSH, and P4. Ovulation times in LL animals varied: l/5 by 1700 proestrus, l/5 by 1000 estrus and 3/5 by 1700 estrus. Serum E2 levels dropped early in some LL animals and late in others. Behavioral estrus was advanced in some LL animals and delayed in others, while activity was delayed in all LL animals. These data suggest: 1. Anovulation occurs in many animals as early as the first cycle in LL, apparently due to the absence of an ovulatory surge of gonadotropina; 2. Many animals exposed to LL show a delay in the timing of the hormonal events of the estrous cycle and ovulation. In spite of this delay, normal temporal relationships between hormonal events appear to be maintained. (Supported by NIH HD 10050 to C.S. Campbell)

CARDIAC RESPONSES T O CHANGES IN VASCOACTIVE STATE. K.Cam bell*, G. Fregin*, S. Waugh* and B. Grant* (SPON: W. Dickson .-J-kx State University, Pullman, WA 99164. Aortic root blood flow; aortic pressure, and central venous pressure (CVP) were measured in chronically-instrumented horses The vasoactive drugs nitroprussideand methoxamine were givento produce graded levels of mean aortic pressure (Pa). Cardiac output (CO), stroke volume (SV) and heart rate (HR)were expressed as functions of Pa. CO was also plotted against CVP. The average power transfer (W) between the left ventricle (LV) and systemic arteries was expressed as a function of total peripheral vascular conductance (TPC). The CO vs CVP relationship was sirn ilar to a venous pressure curve; thus, changes in CVP were not dominant factors in causing changes in CO. CO increased with decreases in Pa below resting levels (hypotension)anddecreased with increases in Pa above resting levels (hypertension).TheCO/ Pa slope in hypertension was significantly steeperthanin hypotension. HR behaved similarly to CO except that HR/Pa slopewas greater in hypotension than in hypertension. In contrast,SV decreased with decreasing Pa in the hypotensive region and also decreased with increasing Pa in the hypertensive region. W decreased with decreases in TPC below resting values and also de creased with increases in TPC above resting values. Thus, the cardiac response to changes in vasoactive state is Pa dependent it is asymmetric with the CO response being more antihypertensive than anti-hypotensive. The HR and SV components of the CO response are quantitatively different. W is maximal andcardiac energy efficiency optimal at normal vasoactive states.

ACTIVE Na AND K TRANSPORT BY THE CORNEAL EPITHELIUM:COUPLING RATIO AND EFFECT OF OUABAIN. O.A. Candia and P. Reinach*. Mount Sinai School of Medicine of CUNY. New York, N.Y. 10029 The tear side of cornea1 epithelial cells is normally impermeable to Na and K and the SCC in isolated corneas bathed in Na2S04 Ringer is less than 2 )IA/cm2. After addition of amphotericin B (lo-5M) the SCC is stimulated to about 20 p/cm 2 for several hs. Unidirectional Na and K fluxes were measured across the cornea1 epithelium before and after stimulation by amphotericin B. Before amphotericin B, Na flUXeS (JNa13 and JNa31; 13 is tear to stroma and 31 is stroma to tear direction) were 8 p/cm2; and K fluxes (JK31 and After amphotericin B, their values JK13) were 0.15 )IA/cm2. were: JNal3, 39 p/cm2; JNa31, 10 )1A/cm2; JK31, 11 p/Cm’; net was 29 p/cm2 and J net was JK13 t 0.65 p/cm2. Ouabain %s4zyareduced JNa net, JK net,Kand SCC 10 p/cm2. to near zero. With 2.5 mM [K) in the bathing solution, the [K) in the epithelial cells was 79 mM before amphotericin B and 15 mM after amphotericin B. Amphotericin B increases Na and K permeability of the tear side of the epithelial cells and allows the Na:K pump located at the stromal side of the epithelial cells to produce a Na and K active transport epithelium. A Na:K coupling ratio of at across the cornea1 least 4:l can be calculated for the Na:K pump of the cornea1 epithelium. (Supported by NIH grants EY-00160 and EY-01976).


CULTURE OF FOLLICLE CELLS FROM A MARINE TELEOST IN SERUM-FREE MEDIUM. P.T. Cardeilhac, A. Wiley* and S.F. Yosha*. Coil. of Vet. Med. and Whitney Marine Lab. U. of Fl.,G'ville, Fl. 32610. Ovarian follicles of the pinfish, Lagodon rhomboides (a sparid fish which lays pelagic eggs) consist of an oocyte surFollicles rounded by 1 to several layers of follicle cells. can be isolated from the ovary by removal of the tunic, trimming away connective tissue and dissecting out ovarian laminae. Follicles are dispersed from the laminae by treatment with 0.25% trypsin and follicle cells are removed from follicles by a second treatment with trypsin. Partially digested follicles are removed by centrifugation at 200 g for 1 minute and follicle cells are removed from the supernatant by centrifugation at 3000 gfor 5 minutes. Follicle cells are washed with phosphate 385 mOsm/liter) and innocubuffered saline solution (pH 7.4, lated into flasks at lo6 cells/25 cm3 surface area. Eagles Minimum Essential Medium (MEM) adjusted to 385 mOsm/liter with NaCl, and buffered with 25 mM HEPES (pH 7.4) was used to culture the cells. Osmolarity was adjusted to approximate the measured osmolarity of pinfish serum. One liter of the medium contained 600 mg NaHC03, 2 g albumin, 5 mg oleate, 500 mg lactalbumin hydrolysate, 50 mg LH, 1.7 mg rogesterone, 1.7 mg !i 0.33 mg estra iol-176, 10 units penicillin, lo5 testosterone, pg streptomycin and 25 x 10 9 pg amphotericin B in one liter. Serum-free medium was 80% as efficient as MEM containing 10% fetal bovine serum based on cell protein production. The addition of albumin and oleate was necessary for cell attachment and the addition of hormones improved growth efficiency of the serum-free medium by 3 fold.



Cynthia Carey and William AXalder III. Dept. of E.P.0 Biology, University ot a01 ado Boulder, 00 80309, and Dept. of E &*E Biology, Universig of'AZ, 85721. Theeggand incubationofthekiwi .=hy=&+=?c ammlouswhenmparedtopredictlons equationsof Rahnandco-workers. Tk incubation period, 1.61 tims expeckd duration, muld result in an excess wabr loss of 61% wm-e it not for a redmtion in waterMPor~~tiVitythatquantitativlelycaunterb~es this longer exposure. We exmined themrpklogical basis for this reduced wility with scanning electmnmicroscapy,usingb~kiwieggshellsfrcsn~chdatahad been previously obtained for water-vapor conductivity or ~~~coxygenuptake,therebycorrela~struct~and function in this unusual species.

PERIPHERAL CHEMORECEPTOR SENSITIVITY TO HYPOXIA FOLLOWING CORONARY OCCLUSION IN DOGS. R. S. Carstens* and C. M. Banerjee. Dept. Physiology and School of Medicine, Southern Illinois Univ., Carbondale, IL 62901. Since hyperpnea following coronary occlusion has been reported in dogs, we wanted to investigate the peripheral chemoreceptor sensitivity to graded hypoxia after coronary occlusion. Twelve mongrel dogs were used for this study. They were divided into two equal groups (a) isocapnic hypoxia where arterial PGo2 was maintained at 40 mm Hg and (b) non-isocapnic hypoxia. Following chloralose anesthesia, the ventilatory responses to graded levels of hypoxia were obtained. Left coronary arterial catheterizations were done under fluoroscopy with image intensification in closed chest dogs breathing ambient air. Acute coronary occlusion was induced by injection of polystyrene microspheres into the left coronary artery (average diameter 500~). The occurrence of myocardial infarction was confirmed by EKG and serum CPK enzyme changes. Following induction of acute coronary occlusion, the ventilatory response to graded hypoxia was again measured. We observed a significant (pc.025) decrease in peripheral chemoreceptor sensitivity to hypoxia following myocardial infarction in both of animals. However groups the response patterns of the two groups were different. The hypoxic response to venti lation was greater in the isocapnic group of animals (pc.001) when compared to the uncontrolled or non- isocapnic animals both before and after coronary occlusion. (Supported in part by grant N-9 P.1 from IHA.)

PURINE NUCLEOTIDE CYCLE ENZYMES IN LIVER AND MUSCLE OF FRESHC. A. Casey* and J. W. Campbell. Dept. of WATER CATFISH. Biology, Rice University, Houston, TX 77001. The purine nucleotide cycle is a major pathway for ammonia release from amino acids in mammalian muscle and brain tissues (Schultz & Lowenstein, J. BioZ. &em. 252, 485 c19761). The cycle has also been considered as a possible alternative to transdeamination for nitrogen catabolism of amino acids in liver tissue of ammonotelic vertebrates. Heretofore however, AMP deaminase was the only enzyme of the cycle that was known to occur in liver of these species. We therefore measured adenylosuccinate (SAMP) synthetase and SAMP lyase in liver as The synwell as muscle of the FW catfish, Ictahrus catus. thetase was measured radiometrically by the conversion of 14c-IMP to l4 C-SAMP and also to 14C-ATP in the presence of The lyase was measured excess lyase and adenylate kinase. spectrophotometrically by the decrease in absorbancy at 280 nm The level of SAMP accompanying the conversion of SAMP to IMP. synthetase in liver averages 0.31 pmole/g tissue/'hr and in The levels of SAMP lyase in muscle, 0.14 umole/g tissue/hr. liver and muscle are 1.9 and 9.7 ymoles/g tissue/hr, respectively. The ratio of synthetase to lyase to AMP deaminase in liver is 1:6:380; in muscle it is 1:69:3306 so SAMP synthetase appears to be limiting in both fish tissues. (Supported by grant PCM 75-13161 from the National Science Foundation.)

EFFECT OF INDEPENDENT CHANGES IN GAS AND HYDROSTATIC PRESSURE ON FISH HEMATOLOGY. E. Casillas*, L.S. Smith, J.J. Woodward*, and B.G. D'Aoust. Fisheries Research Institute, University of Washington, Seattle, WA 98195. Current studies in mammalian hyperbaric physiology must deal with hydrostatic and gas pressure as one variable. Use of f luid-breathing ve rteb rates allows their separation. Salmon were exposed to gas and hydro static pres sure together or independently in a pressure chamb er and thei r blood was serially sampled for two days post-dive. Fish exposed to a normal saturation dive suffered loss of thrombocytes and fibrinogen, prolonged PT times and increased fibrinolytic activity, plasma proteins and erythrocyte counts in proportion to the severity of the dive. Fish exposed to a hydrostatic dive experienced an increase of thrombocytes and available fibrinogen, shortened PT times, increased erythrocyte counts, and dec reased plasma proteins. Trout exposed to a normal saturation dive exhibited selectively increased circulating epinephrine levels during the compression phase of the dive which was ma.intained thro ugh decompression. It appears that hydrostatic pressure induces activation of the blood coagulation system of fish, possibly mediated through ephinephrine release. The activated system may predispose fish to bubbleinduced diffuse intravascular coagulation following rapid decompres sion. Furthermore, hemoconcentration following decompres sion may be a compensatory action to compressioninduced hemodilution and not a response to bubble-induced anoxia. (Supported by NIH Grant HL-16254)

PROSTACYCLIN AND FETAL PULMONARY VASCULAR RESISTANCE. S. Cassin, I. Winikor*, and M.L. Tad*. Dept. Physiology, univ. of Fla., College of Medicine, Gainesville, FL 32610. The effects of prostacyclin (PG12) on pulmonary vascular resistance (PVR) were studied in near term fetal goats and sheep. Fetal animals were delivered by cesarean section with umbilical circulation intact. The left pulmonary artery was perfused at constant flow with blood from the inferior vena cava. Blood flow through the right pulmonary artery andductus arteriosus was left undisturbed. Pulmonary, left atrial, and systemic pressure as well as pulmonary flow along with blood gases and pH were monitored. PG12 produced dose-related decreases in pulmonary vascular resistances in both species in doses of 0.1-28 pg/kg/min. The decrease in PVR at comparable doses was less in fetal sheep lungs which have a lower control PVR than goats. At doses of 0.23 and 0.29 pg/kg/min in goat and sheep respectively we noted a decrease in systemic blood pressure. These data show that PG12 is similar to PGEl in that it has powerful pulmonary vasodilator activity, however, in contrast to PGEl, it is not well metabolizedby fetal lungs. These data also suggest that the systemic hypotensive effect we have observed following intrapulmonary infusion of arachidonic acid may be due to conversion of the acid to PG12. Supported by NIH Grant HL 10834 and the Fla. Heart Division of the American Heart Assoc.





FLOW (ir)



ACIDS AND HEXOSES FROM SEA WATER BY OCTOPOD L. Castille and A. L. Lawrence. Univ. of TX 77004. The uptake of 14 C-labeled amino acids and hexoses byV6 benthic Octopus joubini hatchlings was measured from 10 moles/l solution in sea water. Hexose uptake was also measured in planktonic hatchlings of a different species of octopus. the uptakes of labeled L-valine and aminoiiobutyric In '* 'q;BA) acid were greater than that of 3-7raline and inhibited by the presence of unlabeled L-valine and AIBA respectively. D-glucose uptake was greater than L-glucose and D-mannitol uptakes, and also inhibited by the presence cf unlabeled D-glucose. In the planktonic octopod hatchlings, D-glucose uptake was greater than L-glucose, D-mannitcl, and 3-O-methyl-D-glucose. L-valine, AIBA, and D-glucose are taken up by a mechanism in addition to diffusion. The mechanism is saturable and specific. AIBA is accumulated against its concentration gradient. Little of the measured uptake is due to the bacterial flora associated with the octopod hatchlings. Amino acids and hexoses dissolved in sea water are a potentially important nutritional source to newly hatched octopods. (Supported by grant BMS 75-986’75 from NSF.)


PENDENCE (DD) IN NORMAL MAN. R. G. Castile*, J. R. Rodarte, Mayo Clinic and Foundation. T . A. Wilson and R. E. Hvatt. Rochester, MN. 55901 There is a large variability in ; and DD (V HgOa"ai ) in normal man. To study this we measured lung met a its fn 40 non-smoking males (19-35 yrs) in a body box and obtained air and He02 (80:20) flow-volume curves. Static lung recoil (Pst) at 50% VC, TLC, and quiet breathing resistance.(RL) were each found to correlate significantly (pc.03) with V at 50% VC . The relationship20f2V and Pst has previously been described by Pst = k p V /A +RV where p = density, A = area at equal pressure point and RV is a peripheral pressure loss. Solution of this equation for air and He02 at constant.Pst and R predicts an inverse relationship between DD and V . . Measured at Pst of 8 and 7 cm H2F, DD did indeed fall s?i&.fFcantly (Pc.02) with increasing V . . If it is assumed that peripheral pressure losses (RQ) a?krsmall at these mid-VC We suggest that in this Pst's, V would depend primarily on A. homogeneous group, the subjects with smaller flow-limiting (FL) airways had lower V but higher DD than subjects with larger airways. Conclus@Z* . when the FL site is in the cenand 2) tral airways 1) Pst, TLC, and RL correlate with i DD varies inversely with V . . T#s latter at a given Pst, finding implies that central airway size m$$rplay a significant role in determining DD in normal man. (Supported by grant HL 21584 from NHLBI.)



ATs1LYSIS OF CARDIAC E1JTRAIIIMELJT BY VAGAL STIMUMTIOEJ. B. G. Celler* (SmJ: L.P. Schrarm). Dept. of Bimical Engtimg, Thehns Hopkins Univ. Sch. of l4ad. Baltimre, Md. 21205. Iow frequency stimulation of the vagus in the mammlian heart is knmn to give rise to a paradoxical acceleration in heart rate thought to result frcm the "locking" of the pacemaker rhythm to the stimulus frequency so that over a limited range of frequencies, the two maintain a fixed phase relationship. Since vagal efferent activity normally occurs in bursts synchronized with the cardiac cycle, it has been suggested that entrainmntphencmnamayplay an important part in the stabilization of the pacemaker rhh and in the-prevention of arrhythmias. A detailed analysis of cardiac entrainment effects in the anesthetized dog under normal conditions and following B-adrenergic block is presented in this report, and reveals that during 1:2 and 1:l entrainmnt both the PP and PR intervals exhibit stable and quasi-stable states which maintain remrkably accurate mathematical relationships with the stimulus frequency, and the arrival tim of each stimulus pulse in the cardiac cycle. This phenomon has been rmdeled by considering the cardiac pacemaker as a voltage controlled oscillator operating under certain conditions, as a phase locked loop. These properties are closely related to the kncwn phasic sensitivity of the cardiac pacemaker to the position of the vagal stimulus burst arriving in each cycle and to the intrinsic biophysical properties of pacemaker cells.


IN RUNNING DOGS. P. Cerretelli, C. Marconi*, A. Veicsteinas*, P. Szlyk* and J. Krasney. Centro Studi di Fisiologia de1 Lavoro Muscolare de1 C.N.R., Milan0 (Italy) and Dept. Physiology, SLJNYAB, Buffalo, NY 14214. The overall energy consumption (Vo2tot), and the fraction of it required to sustain pulmonary ventilation (c02vent) and locomotion (iTC210c) were determined on a total of 11 mongrel dogs (11-20 kg) during aerobic treadmill runs at various speeds up to 16 kmehr-l and inclines O-15%. copvent was determined as the product of observed irEBTPs (lamin-I) times the ratio AiTo2/ AVE (ml-l-l). Individual AVO,,/AcE ratios were obtained for each animal at given ex ternal Lwork loads that wer e ac camp anied by VE changes occurring spont aneously or indu ted by P rolo nged low caloric diet or by sino-aortic denervation. In the irE range between 10 and 80 l*min-' both during exercise and recovery A$02/A$E averaged 15 ml of oxvgen per liter ventilation with a tendency towards a marked increase at high respiratory frequencies. . During exercise Vozvent varied between .35 and for work loads below 25% and above 75% of tC2max, -65 of vo2tot respectively. It is concluded that in the dog the efficiency of the ventilatory pump is very low, particularly at high work the efficiency of locomotion (Eloc) loads. As a consequence, increases with increasing speeds at a given incline since Eloc rmechanical work/Vo210c rather than Eloc = mechanical work/ (Supported by Italian Research Council (CNR) and NHLBI vo2tot Grants HL 14414-06, HL 18416-03, and Am. Heart Assn., West. NY Chapt.)

CRYSTALLOID DISTRIBUTION DURING HEMORRHAGE AND FLUID INFUSION IN ANEPHRIC BEAGLES. Arturo Cervera*and Gerald Moss. Center for Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12181. According to the Starling Hypothesis, increasingly larger volumes of fluid accumulate in the interstitium with progressive hemodilution. The interstitial pressure rises stoichiometrically to counterbalance the altered oncotic gradient in maintenance of a stable blood volume. Absence of renal function should not alterthe equilibrium, which was confirmed by this study. Five splenectomized beagles were anesthetized and arterially hemorrhaged by 73% red cell mass in 3 hours. Normovolemia was maintained by lactated Ringer’s solution (LRS)infusion. One month later, snares were loosely placed around the renal pedicles. They were snugged the next day, repeating the previous hemorrhage regimen, infusing the volume of LRS retained. For 73% hemorrhage, normal beagles retained LRS at equilibr?ZZZFre ratio of (7.m1 .2):1 for undiluted shed blood to maintain normovolemia and stable hemodynamics. When physiologica I ly anephri c, this balance of crysta I Ioid infusion to hemorrhage resulted in identical blood volume, Hct, and plasma:interstitial fluid distribution. The lungs showed no edema. The measured volumes of retained fluid at each level of hemodilution were in close agreement with predictions based upon extrapolation of Guyton’s measurements of canine interstitial compliance (7.00 versus 7.43, calculated). The kidneys do not determine the equilibrium, but respond to establish the appropriate level of fluid retention. (Supported by ONR contract NOOO14-76K-0512)

RENAL HANDLING OF HORSERADISH PEROXIDASE. Y. Chan and W. ~~-Straus*. Dept. Physiology and Biophysics, Univ. of Illinois Med. Ctr., and Dept. Biochemistry, Univ. of Health Sciences, Chicago, 111 6OG12 The renal reabsorption and excretion of protein were studied in rats by clearance and biochemical methods using horseradish peroxidase as a tracer protein. The concentration of HRP in the total particulate fractions of the renal cortex was taken as a measure of tubular reabsorption. When HRP was injected together with either Mannitol, or hypertonic saline, or antagonists to histamine and serotonine, the renal clearance of HRP (CHR~) was 7-15% of the inulin clearance (CIN). In these rats, only slight signs of vascular leakage were observed, relatively small amounts of HRP were reabsorbed into the renal cortex, and 40-50% of the protein was excreted in the urine. CHRP amounting to 7-g% of CIN were also obtained when HRP was infused continuously at relatively low dose levels which did not cause vascular leakage. However, when HRP was injected alone at dose levels causing vascular leakage, high concentrations of HRP were found in the renal cortex 15-20 minutes after injection but only a few percent were excreted in the urine. Approximately 30% of the protein was excreted during the following 60 minutes and CHRP then approached normal values. It was suggested that during vascular leakage and the correlated decrease of CIN and urine flow, HRP became highly concentrated in the glomerular filtrate and, therefore, was reabsorbed into the proximal tubule cells in high concentrations.



TERNARY DIFFUSION AND EFFECTIVE DIFFUSION COEFFICIENTS IN ALVEOLAR SPACES. H.K. Chang and L.E. Farhi. BioMedical Eng. Unit & Dept. Physiol., McGill U., Montr6a1, Canada; Dept. State U. of New York at Buffalo, Buffalo, NY 14214. Physiol., Ternary diffusion in alveolar spaces is studied by applying the non-equimolar counter-diffusion theory to a fictitious gas film erected a certain distance away from the alveolar membrane. When the compositions at the two sides of the film are taken to be, respectively, the alveolar gas composition and a proportional mixture of inspired gas with alveolar gas, the resulting fluxes of 02 and CO2 are essentially linearly related to their respective partial pressure gradients. From this linear relationship effective diffusion coefficients may be obtained by simply measuring the slopes of the flux lines. These slopes are affected by the nature of the third gas as shown in the table below:

IN VITRO COMPARISON OF DRUG RESPONSES ON SWINE AND RABBIT AIRWAYS. N. Chand*and L. DeRoth. Departement d’anatomie et de Facul te de Medecine veterinai re, Univerphysiologie animales, site de Montreal, St-Hyacinthe, C.P. 5000, J2S 7C6, Quebec, Canada. PGF2cl, phenylephrine (PE) and bradykinin (BK) contracted Tracheolung strips (LS) of rabbits and neonatal piglets. bronchial smooth muscle (TBSM) of rabbit, neonatal and adult Carbachol conswine were insensitive to 5-HT, PGF20! and BK. tracted TBSM preparations relaxed to PGE , PGE2, isoproterenol and BK. Relaxations to BK were inhibite tl by indomethacin. Mepyramine antagonized contractions to histamine on the airways of these animals. After H1-blockade, carbachol contracted swine relaxed to histamine and 4-methylhistamine TBSM of adult (4-MeH) . These relaxations were inhibited by metiamide (M) or Relaxations to histamine on rabbit trachea cimetidine (C). were resistant to cimetidine, propranolol,indomethacin, aminophylline and trasylol. Phentolamine antagonized contractions This to PE on lung strips of rabbit and neonatal piglet. investigation showed i. the presence of H1-(excitatory) histamine receptors; i i. H,-inhibitory receptors in the TBSM of adult swine; iii. a-a8renoceptors mediating constriction of exi Speripheral ai rways of rabbit and neonates. The poss ible tence of H,-i sorecepto rs (H,?) in rabbit trachea is stro ndy suggested.L(Supported by Agficulture Canada Grant).

Mixture 02-C02-He

BLOOD FLOW AND OXYCEN UPTAKE IN ISOLATED CANINE SKELETAL MUSCLE DURING ACUTE ANEMIA. C.K. Chapler and S.M. Cain. Depts. of Physiology, Oueen's University, Kingston, Ont. K7L 3N6 and University of Alabama in Birmingham, AL. 35294. The metabolic demands placed on the oxygen transport system by skeletal muscle during, acute anemia were studied in 8 anesthetized dogs. Venous outflow from the gastrocnemius-plantaris muscle group was isolated. Values for muscle blood flow and oxygen uptake, cardiac output (C.0.) and total body oxygen uptake (902) were obtained during a control period and at 30 minutes of acute anemia (Hct. = 14%) produced by dextran-for-blood exchange. A second group of 4 animals received propranolol (1 rng/kp> IV) 20 minutes prior to the control measurements. Muscle blood flow and C.O. increased (p < 0.01) 70 and 88% respectively in the untreated groun at 30 minutes of anemi a; s imil ar increases w ere observed in tile beta-blocked animal S. Both total or t were decreased to 50% of the body and must le oxypen transp control value s at 30 m i .nutes of anemi a (D < 0.01 ). Most surnrisinp, in untreated animals, was an increase in muscle oxygen uptake from 5.1 to 7.4 ul/g muscle/min (p < 0.05) at 30 minutes of anemia dcsnite the fact that VO2 remained at the pre-anemic Muscle oxypen uptake did not increase in 3 of 4 control value. pronranolol treated animals at 30 minutes of anemia. The data demands demonstrate that skeletal muscle increased its oxygen in acute anemia and that the increase in muscle oxygen untake occurred at the expense of other tissues. (SuDDorted by the Ontario Heart Foundation and NHLBI 14G93).






O2 co,


O2 co,


0.5303 0.4380 0.2442 0.1768 0.1431 0.0962

02 CO2

SMALL BOLJEL CANINE ACTION AND PACESETTER POTENTIAL RELATIONSHIP DURING THE INTERDIGESTIVE HOUSEKEEPER: *I.Charuzi, C.F.Code and P.C.O'Brien*, Mayo Foundation, Rochester, MN 55901 and CURE UCLA and VA-Madsworth Hospital Center, Los Angeles, CA 90073. Small bowel action potentials (APs) and pacesetter potentials (PPs) were recorded simultaneously on recilinear penwriter and analog tape recorders from 4 fasted, healthy, conscious female dogs trained to stand quietly while supported by slings in Pavlov-type stands. Silver-silver chloride electrodes were sewn to the serosal surface of the bowel at least 2 wks. before observations were started. Five activity fronts (Phase III), recorded from each dog, were submitted to computer assisted analysis. The mean number of PPs comprising the activity fronts was 87 in the duodenum and 66 in the rest of the bowel. The temporal relationship between onset of each PP of a front and the onset of the burst of APs the PP cycle supported was constant in the duodenum, but in the mid and distal small bowel the interval was at first shortened and then lenghtened as successive PPs of the front swept past a recording site. This shift in interval may be responsible for a change in character of the peristaltic contractions comprising the fronts in the distal bowel.

OF INFLAMMATORY CELLS INFILTRATING R.E. Chatelain,* A.R. Vessey: C.11. Ferrario. Cleveland Clinic Research Ohio 44106.








COOLING: THE PRIMARY STIMLBX3 FOR EXERCISE-INDUCED W. Y. m*, P. C. wiser and H. Chai*. National Center, Denver, Colorado 80204

To determine whether respiratory heat loss or respiratory water loss was the stimulus for exercise-induced asthma (EIA), 5 patientswere studiedusingarandanly assigned sequence of

The in vitro induction of lymphocyte blast transformation and proliferation by mitogenic substances is an expression of the --in vivo circumstances. To assess the immunological reactivity of mononuclear cells infiltrating vascular lesions, renal hypertension was induced in 108 Sprague Dawley rats by Sixty days aortic coarctation between the two renal arteries. after (207 + G SE m m Hg mean blood pressure), infiltrative The cells were freed from vascular lesions were isolated. the arterial wall, purified on Ficoll-H paque gradients, and The T-cell micultivated at a concentration of 6 x 10 8 /ml. togen concanavalin A (Con-A) or the B-cell mitogen dgxtran sulfate (US) were added to cultures (Con A = 4 ug/lO cells; DS = 100 pg/ml). Forty-eight to 72 hr later the cells were pulsed with 3H-thynlidine. Increased mitotic activity was demonstrated by increased thymidine incorporation (Con-A: 11,910 + 2425 cpm; US: 12,960 + 248 cpm; unstimulated cultures: 356 + 54 cpm). These results indicate that a significant portion of the hypertensive cellular infiltrate has Tand B-cell-like reactivity and suggest that these cells may participate in immunologically mediated injury of the vessel wall. (Supported in part by grants of NHLBI, #HL 6835, and #HL-18062).

4 inspired-air






for 10 min. Tk 4 inspired-air conditions were: (1) Cool, dry roan air (CDA) at 23OC with 3 q of water and 7.3 cal of heat -tent/l, (2) over-saturated air (OSA) at rocxn temperature containing 43 mg water and 16.3 cal/l,(3) hot, dry air (HDA) at 120°C having 3 mg water and 24.4 Cal/l,. and (4) warm, humidified air (WHA) at 37OC with 43 rrg water and 34.7 Cal/l. Using inspired-air CDA and OSA, all patients mnifested EIA while forcedexpiratoryvolurre inlsec (F'EV1) and maximal mid-expiratory flaw (M4EF') decreased to an average of 81% and 63% of the respective baseline ken breathing CDA and to 83% and 71% of the respective F'EVl andM!@Fbaselinewhenbreathing OSA. With M-IA, EIA was clearly prevented while the postexercise FEVl and kMEF were 101% and 103% of baseline, respectively. With HDA, the post-exercise FEVl and M@F were 95% and 86% of baseline, respectively. Analysis of variance reVealed that the post-exercise pulmonary function changes had ~SUltE?d solely from respiratory heat loss and not frcxn water loss or frm interaction of heat and water losses. These results indicate that exercise-induced asthmis associated with airway cooling incurred during exercise rather than airway dehydration. (Supported by USPHS grant NHIBI 21126-01) 19

PULMONARY EXTRACTION OF ALIPHATIC ALCOHOLS IN VIVO IN DOGS. F. P. Chinard, A. B. Ritter*, W. Cua*and A. C. Delea*. Depts. Medicine and Physjology, CMDNJ-New Jersey Medical Schhol, Newark, NJ, 07103.

THE EFFECT OF HYPEROXIA AND HYPERBARIA ON TRANSMURAL MYOCARDIAL BLOOD FLOW IN THE AWAKE DOG W.R. Chitwood, Jr.*, R.C. Hill*, J.D. Sink*, H.A. Saltzman, Departments of Surgery and Medicine, Duke and A.S. Wechsler*, University Medical Center, Durham, North Carolina 27710 Previous studies have demonstrated that a high Pa02 is associated with reduced total coronary blood flow (CBF). Inter-relationships were further assessed by computing transmural myocardial blood flow (TBF) in 8 awake chronically instrumented paced (P) and unpaced (U) dogs by injection of 8u microspheres, under control conditions (breathing air at sea level), and at 3.5 ATA breathing either an air equivalent gas (7.5% 02) or 100% 02 (HBo). Both ventricular and aortic were measured and remained unchanged from control pressures t SEM. under all conditions. Flow data = m l/min/gram Control P 3.5ATA-7.5%02 P 3.5ATA-100%07 .98+.14NS P Epi .61?.08 .88_+.09 c.005 Endo 1.21k.23 NS 1.05k.11 c.01 .74*.08

Extractions (E) and calculated permeabflities (P) of aliphatic alcohols and terminal diols increase with increasing molecular weights and oil:water djstribution coefficients; recoveries relative to reference vascular (T-1824,'=?-HSA) and extravascular (THO) indicators average unity; mean transft times (F) and outflow curves converge on corresponding THO parameters with increasing molecular weight (Am. J. Ph)asjol. 230:1708-1721, 1976). With the aliphatic alcohol series (C, C+ rnd through CO), E's are less than ETWO for C, through increase regularly and markedly from C$-through CQ , equalfng ETuofor C. and exceeding EnK, for CG through C, . Mean tranzit times equal (C, through Cd ), then exceed (Csthrough C9 ) trwd CC and decrease for C, Recoverieq,R, equal Rm,for C, through RBC permeabilities to the through CT . Rcg averages 0.6. alcohols C, through Cb are of the same order as Pr,d;,& orders of magnitude larger (Garrjck, pers. Corn.) and two than endothelial PN~+. Therefore, red cell trappjng is unlikely. The Increasing E's and decreasing R's of the alcohols oil:water distribution coefwith higher M. W. and wj th high fjcients may represent jncreasing endothellal permeabilities and/or increasing volumes of equilibrated distribution. If the the alcohols equilibrate into a geometric volume greater last, and a lipid compartment. than the vascular exchange volume

U Epi 1.262.19 NS 1.13k.15 c.01 .85?.11 1.332.20 NS Endo 1.052.08 1.43i.20 c.04 7423 NS Pa02 (~g) c.001 19332106 7323 The significant decrease in CBF during HBO was independent This from changes in heart rate or barometric pressure. decrease in TBF during hyperbaric oxygenation reflects increased vascular resistance within the myocardium. However, endocardial flow was maintained (AEndo/Epi=NS) at levels not associated with subendocardial ischemia.


EFFECT OF PROSTAGLANDIN SYNTHETASE INHIBITION ON POTASSIUM EXCRETION. D. Chock,* C.M. Huang,* A. Quintanilla,* J. Sporn* and F. de1 Greco. Section of Nephrology, V.A. Lakeside Hosp. and Northwestern University Med. School, Chicago, Ill. 60611. Factors known to affect K tubular secretion include distal Na delivery and aldosterone. Indomethacin (Indo), a prostaglandin synthetase inhib itor, has been repor ted to increase serum K (SK), effec .t whi ch wa s at tribu ted to aldos terone inhibition. To reexamine this ques tion 5 dogs underwent adrenalectomy and partial renal artery liga tion to induce mild renal insufficiency. After full surgical recovery and treatment with replacement doses of prednisone and fludrocortisone acetate, Blood and urine mild hyperkalemia was induced by KC1 infusion. samples were collected serially. The following day the study was repeated after administration of Indo, 5 mg/kg. Mean SK and urine Na/K ratios were as follows: Time (min) 0 15 30 60 90 120 SK UNa'UK

Control Indo

4.7 4.6

4.7 4.6

4.8 4.8

4.8 5.1*

4.9 5.7**

5.0 5.7**

Control Indo

5.3 5.4

5.4 5.4

5.4 4.8

5.1 3.2*

4.6* 2.7*

4.8 2.8*





Castleman and J.P.Van USC, Los Angeles, and Jet Propulsion The effect of hypogravity during


MUSCLE. L. Neurology,



spaceflight was studied on must le. Five ma le Wistar rat striate rats aboard the biosatellite Cosmos 936 (Group FSO) subjected to hypogravity for 18.5 days were sacrificed approximately 10 hr after recovery. The right extensor digitorum longus (EDL) muscle was removed and histochemica lly processed for alkal ine adenosine tri(PH 9.4) phosphotase, nicotinamide ide adenine d inuc leot and periodic acid schiff. An additional five synchronous stationary (SSO) and five vivarium-housed animals (VO) were included as controls.

Muscle fiber uere analyzed fibers were technique. Am (0.87 the VO groups of the shortening


*P f!.05). In other reoion(YE was significantly lows than the SA node (P4.05); corresponding values of kNE averaged C.O46+%olg in the atrioventricular node, 0.040+0.006 in the left atria1 appendage, O.n3fl+O.n05 in the right ventricle, and 0.035+0.005 in the left ventricle. These data indicate that sympathetic cfferent neural activity to the SA node exceeds that to other heart regions. Thus, nonuniform control of heart regions is mediated by central as well as peripheral mechanisms.


DOPAMINE INHIBITION AND CAROTID BODY CO2 TRANSDUCTION. D.F. Donnelly*, P.J. Feustel*, J.M. Adams*, E.J. Smith* and R.E. Dutton. Department of Physiology, Albany Medical College, Albany, N.Y. 12208. Dopamine occurs in high concentrations in carotid body type I cells and has been hypothesized to be a modulator of chemoreceptor activity. We wished to investigate the effect of dopamine blockade by haloperidol on afferent activity. Single carotid body nerve fibers were dissected free and placed on unipolar platinum wire electrodes in pentobarbital anesthetized cats. After placement on a respirator, the response to room air and the last two min of 6 min inhalation of 3, 6 and 9% FICO2 were recorded and blood samples drawn for gas tension measurements. Haloperidol was administered at 250 ug/kg, a dose shown to block the inhibitory effect of dopamine (Bisgard et g., Fed. Proc. 37:904, 1978). Following 15 min equilibration, the CO2 response was again tested. If at any time the blood pressure fell below 80 mm Hg, the experiment was terminated. In all 6 cats there was an increase in basal discharge rate following haloperidol; however, the CO2 sensitivity was unchanged (p>.8). For example, one fiber showed an increase in basal discharge frequency from 150/minute to 275;minute following dopamine blockade. The CO2 sensitivity was unchanged, going from 24 to 23 impulses/minute/nM H+. The results suggest that dopamine tonically inhibits afferent activity but is not a primary mediator of the hypercapnic sensitivity. (Supported by NIH HL-12564 and HL-07194)

ROLE OF ARTERIAL BARORECEPTORS AND EFFECTS OF HYPOTENSIVE AGENT CLONIDINE ON CEREBELLAR-ACTIVATED SYMPATHETIC NERVES. K.J. Dormer*, R.D. Foreman and C.A. Ohata*. Dept. of Physiology, Univ. of Oklahoma Health Sciences Ctr., Oklahoma City, OK 73190. Activity in thoracic sympathetic preganglionic nerves from stimulation of the fastigial nucleus (FN) was recorded during normal and elevated arterial pressures, and during isolation of the carotid sinuses. The hypotensive action of clonidine (CL) was correlated with lowered resting and evoked sympathetic activity. Chloralose-anesthetized dogs were implanted with electrodes and at an FN site which evoked tachycardia and hypertension at 80 Hz stimulation. Teased fibers of the T-3 nerve were placed on bipolar recording electrodes. Occluders were positioned around the common, external and internal carotid arteries. Digitally computed post-stimulus histograms show progressively reduced nerve activity as mean arterial pressure increased from 90-175 mm Hg during phenylephrine infusion (0.2 mg/min). T-3 activity at 0.3 Hz stimulation was reduced 15-20% during elevated pressures but bilateral carotid isolation prior to phenylephrine produced spike activity at or above control values. Clonidine (5-20 pg/kg) reduced resting activity more than 50% after 10 ug/kg) and FN-evoked activity was almost abolished after 20 pg/kg. Evoked T-3 activity from stimulation of the dorsolateral funiculus at C-7 was reduced more than 50% after 15 ug/kg CL. We conclude that the cerebellar-evoked sympathetic activity is reduced by baroreceptor activity and CL but the latter occurs at the spinal level as well as at central sites. (Supported by NIH Grants 11255 and HL 05145.)


THE EFFECT OF INSPIRATORY FLOW RATE ON THE ESOPHAGEAL PRESSURE GRADIENT IN UPRIGHT HUMANS. J. Dosman ,* W. Hodgson,* C. Edwardson.* D. Stirling.* B. Graham* and D. Cotton* (SPON: J. Phillis). University Hospital, University of Saskatchewan, Saskatoon, Canada S7N OW8. We measured pressures in 2 lung regions in 5 seated subjects with 2 esophageal balloons placed 7.2 + 0.6 cm (mean f gra 1SE) apart in the mid-esophagus, The esophageal pressure dient (EPG), transdiaphragmatic pressure (Pdi) and gastric pressure (Pgas) were obtained. Inspiratory maneuvers were made from FRC at low inspiratory flow rates (slow +I) (mean slow fI: 0.29 ? 0.27 lps) and at rapid flow rates (fast OI) (2.57 i 0.14 1~s). At FRC the mean EPG was 0.20 2 0.32 cm The mean EPG was consistently lower at 500 cc H20/cm. above FRC during fast VI (0.13 + 0.07 cm H20/cm) than during slow VI (0.27 2 0.05 cm H20/cm) (p < ,001, paired II t II test). In 3 subjects the reduction in EPG with fast ;I as compared to slow VI was associated with significant rises in Pdi. reduction in EPG with fast +I was In 2 subjects, associated with low Pdi and a decrease in Pgas. During fast tI with high Pdi, EPG was lower than during fast tI with low Fast $I appears to result in amplification of pressure Pdi. in the lower as compared to the upper region with reduction in EPG. Diaphragmatic contract+on appears to influence alterations in EPG during fast VI but reduction in EPG may occur with low Pdi. (Supported by MRC Canada and the Saskatchewan Anti-Tuberculosis League.)

ALTERATIONS IN ‘IHE CARDIAC ACTION POTENTIAL PRODUCED BY HYDROSTATIC PRESSURE. T. J. Doubt* and P. M. Ho an Physiology, SUNY at Buffalo, kuffaldi4 Depto Of Previous work from this laboratory’h& shown that hydrostatic pressure increases refractoriness and slows conduction in cardiac muscle. The present study using microelectrode techniques was undertaken to determine the cellular bases for these effects. Canine Purkin j e fibers , at 37oC, were exposed to increases in hydrostatic pressure to 150 ATA. Action potential duration (APD) increased significantly at 150 ATA. APD at -20 averaged17,14and13% mv, -60 mV and at maximum repolarization longer than their respective 1 ATA values. At 150 ATA the curve relating maximum upstroke velocity (Vma) to take-off potential was shifted downward indicating a decrease in membrane responsiveness. At fully polarized levels of membrane potential 0 ma decreased by 9%, a reduction coincident with a 15% increase in conduction time. These changes in APD and responsiveness explain, in part, pressure-induced changes in refractoriness and conduction. The present findings further support the notion that pressure acts both on steady-state and kinetic variables involved in the genesis of cardiac action potentials. (Supported by USPHS Grants HL 16135, PO1 HL 14414, and HL 15194.)

TEMPERATURE-PRESSURE INFLUENCES ON CARDIAC CONWCTION. T. J. Doubt and P. M. Ho an* Dept. of Physiology, SUNY at Buffalo, Buffalo-4. Changes in either temperature (T) or hydrostatic pressure

ENDOTHELIAL REGENERATION IN AORTAS OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS. Ben H. Douglas, Allen D. Ashburn*, and R. J. Bull*. Dept. of Anatomy, University of Miss. Medical Center, Jackson, Ms. 39216. The present study was designed to examine the repair of the aortic lining in normotensive control rats (NCR) and spontaneously hypertensive rats (SHR) following mechanical denudation of the endothelium. Fifteen NCR and 20 SHR weighing 250-350 g were used. The blood pressure of the NCR was 123 2 3 mmHg and of the SHR was 202 ,+ 11 mmHg. The endothelium was denuded as follows. A 2F Fogarty embolectomy catheter was inserted into the carotid artery and advanced until the tip was estimated to be approximately at the bifurcation of the aorta. The baloon at the catheter tip was inflated and withdrawn until the tip was at the origin of the left carotid artery. Samples of tissue for histological examination were taken after 1 hour, 3 days, 1 week, 2 weeks, and 3 weeks. Examination of aortic tissue taken after 1 hour indicated that this was an effective method of endothelial removal. Rare groups of endothelial cells were found on the denuded surface. Platelet thrombi were not observed to form on the denuded surface of the aortas of either the NCR or the SHR. Endothelial regeneration occurred in both the NCR and the SHR. Myointimal thickening occurred but was not made more severe by the hypertension. If the extent of myointimal thickening was influenced by the insudation of materials from the lumen provoking cellular proliferation in the arterial wall, hypertension appeared not to alter the process.

(P) can modify impulse propagation in the heart. The present study was designed to assess the interplay between thesebasic environmental and rabbit

factors in atria1 muscle

determining cardiac conduction. and dog Purkinje fibers were

Dog tested

at various temperatures and pressures. In all cases decreases in temperature from 37-27oC and increases in pressure from l150 ATA lengthened conduction time. Furthermore Qlo's calculated for this temperature range were greater at 150 ATA than at 1 ATA indicating a pressure-induced potentiation of the conduction response to decreasing temperature. 1 ATA


150 ATA

Rabbit Atrium 1.7139 Dog Atrium 1.6606 Dog Purkinje 1.7086 In all tissues, the action in the T range of 37-40°C. erature

volved Grants

2.6849* 2.0974* *p to assess antioxidant capabilities in buffering such toxic reactive species. Male stumptail macaques (Macaca Arctoides) (6-14 kg.) are exposed 7 days/week to CS. Daily consumption of 3-12 cigarettes compares to 1 pack/day and 3 packs/day for low-dose (LS) and high-dose (HS) smokers, respectively. AM obtained by bronchopulmonary lavage with saline are counted and prepared in an acid lysate for total glutathione (TG) measurements and a freeze-thaw lysate supernatant for enzymatic assays. Specific activities (SA, nmoles NADPH oxidized/mg protein/min) for glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), and TG (ngrams/mg protein) are compared below for HS, LS, and controls (C): G6PD 6PGD Glutathione % Control SA % Control SA % Control HS 14 SAll* 280 93 + 37* 150 4.4 + 1.1+ 142 103 LS 10 3 5* 200 69 + 27 111 3.1 + 0.8 C 5f 3 62 3 23 3.0 2 0.7 's t test (Signif icant differences from control using Student (.02 500 while at 4' it was < 50. Maximum M/S ratios were obtained at a concentration of 0.1 mM DD1251SA. When disrupted ER were incubated at 37' with DD12' ISA the majority of the marker was incorporated into the soluble proteins (M/S ratio = 0.14). Results suggest that DD125 ISA used under the appropriate conditions, including the removal of unreacted label with a-naphthol, can serve as a highly selective plasma membrane marker with minimal penetration and labeling of intracellular proteins. (Supported by NIH grant AM-16105, by AHAand by Mayo Foundation.)

CEREBROSPINAL FLUID BICARBONATE AND ELECTROLYTE REGULATION IN INTENSIVE CARE NURSERY (ICN) NEONATES. William H. Edwards*,E.E. Nattie,George A. Little *. Depts. of Physiology and Maternal and Child Health, Dartmouth Medical School, Hanover, N.H. 03755. CSF was obtained for clinical indications in 120 ICN babies of BW 930-409Og and gest. age of 26-42 wk. CSF HCOS determined from total CO was compared with plasma HCO? calculated from pH an 2 PC02. CSF electrolytes were compared with same day plasma values. 24 babies with data appropriate for analysis of CSF HCO; regulation were divided into 3 groups:I, a refer ence group without birth asphyxia(BA=APGAR scores < 4 at 1" or O.O5) PcO.02) and dog Pa (A%+356; PcO.02) while both rat (A%+251; showed significant increases in CAMP levels. Results show that major differences in responsiveness of renal AC to VP, PTH and CT exist between rat, rabbit and dog, primarily in Md and Pa, which consequently may reflect differences in CAMPmediated hormonal regulation of fluid and electrolyte excretion between these three experimental animal models. (Supperted by AM-16105, AM-21114, AHA& the Mayo Foundation.)



RENAL AUTOREGULATING TIME COURSE WITH CONVERTING ENZYME BLOCKER SQ 14,225. T.E. Jackson* and A.C. Guyton. Dept. Physiology & Biophysics, Univ. Med. Cntr., Jackson, MS 39216 Step decreases from 110 m m Hg to 80 m m Hg in renal arterial pressure were effected for 60 min. under two conditions in anesthetized dogs. Group 1 utilized the normal hydropenic dog and group 2 utilized the normal hydropenic dog treated with converting enzyme blocker SQ 14,225. Group 1 demonstrated autoregulation of renal blood flow (RBF) within 1 min. and autoregulation of glomerular filtration rate (GFR) within 5 min. During the 60 min. observation, Group 1 RBF decreased to 78% of control while GFR remained autoregulated to control. Group 2 autoregulated RBF within 1 min. and remained at control level for the entire 60 min. observation. Likewise, GFR was autoregulated within 5 min. and remained autoregulated during the entire 60 min. period. Calculated estimates of afferent and efferent resistance indicate that afferent resistance was stable during the pressure decrease in both normal and blocked animals. Calculated efferent resistance during the same time rose about 40% in the normal group, but remained stable in the blocked group. These results suggest that the time dependent characteristic autoregulation of RBF and GFR in normal dogs during a decrease in arterial pressure is due to the influence of angiotensin 11 on efferent resistance. (Supported by NIH grant HL 11678)

WATER EXCHANGE ACROSS FISH GILLS. W.F. Jackson and P.O. Fromm. Dept. Physiology, Michigan State University, East Lansing, Mi. 48824. The effects of varied environmental osmotic pressure on tritiated water (HTO) influx (Jw*) across isolated perfused gills of rainbow trout was investigated. Variation in bath osmotic pressure from 40 to 600 mOsm/kg using NaCl had no effect of Jw* in gill arches perfused with Cortland saline containing 3 gm% bovine albumin (275 mOsm/kg) with or without 10a5M epinephrine (epi). These results verify the assumpt ion that fo r all practical purposes Jw* is sole1 Ya measure of the dif fusion of HTO a cross the gill. With this in mind the diffusive permeability-surface area product (PdmA) for HTO was calculated at various perfusion flow rates from .05 to .45 ml min-I. Without epi in the perfusate, gill arches perfused at flow rates greater than or had a constant Pd*A of 3.1 x 10m4cm3 equal to .18 ml min-l set -1 , whereas, for those perfused at .05 ml min-l Pd*A was reduced by 30%. Gills perfused with epi responded differPd*A increased as flow increased from 6.8 x 10s4 ently. cm3sec -1 at .05 ml mine1 to 12.1 x 10-4cm3sec-1 at .45 ml min -1 . This indicates that assumption of a constant area term when calculating permeability constants may not be valid, and could lead to erroneous conclusions. (Supported by grant ENV77-12300 from NSF).

EFFECTS OF SLEEP STATE ON VENTILATION AND C02RESPONSES IN THE J. P. Jackyf: (SPON: W. G. Guntheroth). Dept. INFANT MONKEY. Pediatrics, Univ. of Washington, Seattle, Wash. 98195. In order to determine whether sensitivity to CO differs between rapid eye movement (REM) and non-REM (NREM)2sleep in newborns, steady-state ventilatory responses to inhaled CO2 were measured plethysmographically during 33 experiments in 7 infant pigtail monkeys in the first through eighth postnatal Ventilation while breathing air during NREM sleep was weeks. 275t13 ml/min/kg (mean+SE) and respiratory rate was 82t3 b/min. Dur&g REM, ventilation increased (Pj.0005) by 64t4 mi/min/kg and respiratory rate fell (P,C.OOOS) by 5 tl b/min, Infants usually did not increase ventilation below-2% FIC02; above this threshold, ventilation during NREM increased with little or no increase in respiratory rate with slope 2421 ml/min/kg/ Responses torr and intercept 462t18 ml/min/kg at 3% FIC02. was elevated by 64t were similar during FXF, but the intercept 5 ml/min/kg (Ps.0005) while the slope fell by 7~1 ml/min/kg/Consequently, most of the REM response curve torr (Ps .0005). lies above the NREM response curve, but at elevated CO2 the It can be concl u ded that i n the infant monkey two converge. the stimulus which is responsible for the increased ventilation seen during REM sleep is not additive with the CO stimuit produces the largest increases in ven z ilation lus; instead, during air breathing and smaller increases when ventilation in elevated by CO2 inhalation.

TEMPERATURE SENSITIVITY OF THE SARCOLEMMAL SODIUM-POTASSIUM PUMP IN CANINE PAPILLARY MUSCLE. J.M. Jaeger*, S.R. Houser & A.R. Freeman, Dept. of Physiol., Temple Univ. Schl. of Med., Philadelphia, ?a. 19140. The temperature sensitivity of sarcolemmal Na-K pump actiusing a new electrophysiological vity (Apump) was investigated technique. Canine right ventricular papillary muscles were externally stimulated at various rates and durations and then allowed to return to quiesence Transmembrane potential s were simultaneously meas ured usin g s tandard microelectrode techniques. The preparation was superfused with oxygenated Tyrode's solution (Kbath = 5.4mM) maintained at the desired temperature (+.5(v). During the drive period, the maximum diastolic potential (Emax) depolarized initially then hyperpolarized. Termination of the drive resulted in further hyperpolarization followed by a slow return to pre-drive values. The observed linear depolarization of Emax (dEmax/(dt)o) with drive is attributed to K+ accumulation outside the membrane and the hyperpolarization to Apump. Since Emax approximates the K+ equilibrium potential and assuming a constant internal K+ concentration, the Nernst equation approximates Ith muscle tone in response to B(Aided by NIH grant HG16710, AHA 76 848 and GH?! agonists. Inwstigatm ward - R(cIK). I (10-7M)+H

AGE INFLUENCES PROPRANOLOL PROTECTION AGAINST HYPOXIA IN RATS. Bernard Karol* and David Laman* (SPON: Paul Nathan). St. Louis VAH, St. Louis Univ. and Washington Univ. Schools of Medicine, St. Louis, MO 63125. Previous studies show that propranolol (P) protects 24 month male rats against depression of spontaneous motor activity (MA) produced by a lo-min. hypoxia (H). We have examined the effects of P (20 mg/kg. s.c., 24-hrs. pre-H; and followed by 10 mg/kg. i.p., 30-min. pre-H) on a lo-min MA obtained lo-min. after H (5-min. of 02:N2 of 5:95%; followed by 5-min. of 3.5:96.5% mixture) in 12 month and 24 day old rats. Air (A) and saline served as treatment controls. Each age population contained 15 rats in four subgroups of PA, PH, SA, SH. For the 12 month adults, P significantly antagonized the H-induced reduction in MA (SH: 241+48; PH: 425+59 counts/ lo-min., pc.O25), while insignificantly altering the MA obtained after A (SA: 741251; PA: 608263). In the infants P failed to protect against the H-induced reduction of MA, and in fact significantly depressed MA (SH: 672265; PH: 437+46, pc.01) without altering the MA after A (SA: 796559; PA:-7882 41). P treatment was associated with a polycythemic response fter H in the in the i nfan ts a fter H and A, but only appeared a inf ants. The se f indings indicate that 1) infants rats are more tolerant of hypoxia than adults; 2) P has an adverse effect on MA in infants, which may be related to beta-adrenergic blockade and 3) P protects against H-induced reduction in MA in adults, an effect probably independent of beta-blockade.

IN Soliman.

The Uptake of corticosterone was investigated in adult male Spraque-Dawley rats in response to ether stress, epinephrine and/or dexamethasone administration. In this study 209 flzi/kg of 3H-corticosterone was used. Tissue: plasma ratios \qere determined in 5 body tissues and in 5 brain regions. These ratios in response to 1.5 min. ether stress were for the liver 3.14; kidney 1.84; spleen 0.43; gut 2.36 and adrenal 1.94 and the same ratios for the control animals were 2.36; 1.97; 0.41; 2.31 and 1.83 respectively. In the brain regions ratios of the stressed animals were cortex 0.18; midbrain 0.23; cerebellum 0.23; caudate nucleus 0.29 and pons 0.27. These ratios for the control group were 9.23; 0.22; 0.23; 0.25 and 0.26 respectively. Plasma H-corticosterone count in the stressed rats were twice as much as the control animals. However, when epinephrine 1 mg/kg) was injected, the tissue: plasma ratios of s H-corticosterone were significantly lower (P % .35) than that of the dexamethasone (1 mg/kg) treated group or the control group. The results of this study suggest the possible influence of the adrenal medulla on the circulating levels of corticosterone. (Supported by NASA grant MG 2183).

NON-VAGALLY MEDIATED BRADYCARDIA DURING CARDIAC TAMPONADE OR SEVERE HYPOTENSION. D.R. Kostreva, A. Castaner*, and J.P. Kampine. Med. Col. of Wisconsin and Wood VA Ctr., Milwaukee, WI 53193. Bradycardia was observed within the first minute of severe hypotension produced either by cardiac tamponade or hemorrhage in vagotomized, sympathectomized and atropinized mongrel dogs anesthetized with sodium pentobarbital (30 mg/kg i.v.). A lead II electrocardiogram, heart rate blood pressure (HR) , systemic (BP), central venous pressure and cardiac vagal efferent nerve activity (CVENA) were all recorded using a polygraph. In one group of dogs a pressurized hemorrhage bottle was connected to both femoral arteries, to effect rapid and sustained changes in BP. In another group of dogs BP was decreased usi .ng an exper imental card iac tamponade (CT) technique. In both groups as BP was rapidly decreased to 15-20 mmHg, HR initially increased and then began to decrease. CVENA increased markedly within the first 10 set of hypotension and preceeded the onset of bradycardia. Bilateral sympathectomy eliminated the initial tachycardia. Bilateral cervical vagotomy and or atropine (0 .5 mg/kg i.v.) did not eliminate the bradycardia . HR returned to control levels as BP was increased. Thi s study has demonstrated that the bradycardia observed dur ing (CT) and or severe hypotension may not be mediated entirely by vagal mechanisms but may be associated with sinus node hypoxia or some other intrinsic cardiac mechanism. (Supported by Grant HL 16511 and Young Investigator Award HL 21042 from HLBI, and the Medical Research Service of the VA).

REDUCTION IN SERUM GASTRIN CONCEHTRATION INDUCED BY GASTRIC DISTENSION WITH WATER OR SALIi;E. Pittengerk --P.C. -- Kothary,*G. - --__--and R.G. Fiddian-Green*(Sponsor: H. Davenport); Department of Surgery, The University of Michigan, Ann Arbor, MI 45109 Gastric secretory studies have been performed on 66 healthy subjects and on 1 patient with the Zollinger-Ellison syndrome (ZES) using the intragastric titration technique. During these studies 500ml of test fluid was introduced into the stomach and reaspirated every 10 minutes. Samples of serum were collected for the immunoassay of gastrin before fluid was introduced into the stomach and during the second 10 minute test period. Distension with water at pH 7 in 37 subjects reduced the serum gastrin concentration (SG) from 10025.8 to 90*5.6pg/ml (10.5% reduction; p5.0 g was 115+30 S.D./45 min at 350 ug/Kg. After crushing the vagi the peak frequency was 202+27/45 min at 200 pg/Kg/ Gastric acid output reached a peak at 1.6+1.0 mEq/45 min at a dose of 200 pg/Kg in intact cats and was-O.73 +0.58 mEq/45 min at 200 pg/Kg in cats with the vagi crushed Tp>O.OS). At 100 ug/Kg in intact cats only 5+5 contractions occurred in 45 min. The present results suggest that after crushing the vagi, antral contractions become more sensitive to cholinergic stimulation while acid secretion remains unchanged. Therefore crushing the cervical vagi alters the relative responsiveness of the secretory and motor function of the stomach to cholinergic stimuli in vivo. (Supported by grant 2ROl AM14563 from NIAMDD). -

MONOPHOSPHATE --IN VITRO EVIDENCE FOR CYCLIC 3'5'-ADENOSINE MEDIATION OF THE EFFECTS OF ISOPROTERENOL AND DOPAMINE ON RENIN RELEASE. G.A. Lopez, F. Romano*, V.A. Aletich*, and L.M. Lissuzzo*. Dept. of Biology, Loyola University of Chicago, Chicago, Illinois 60626. The effect of adrenergic-receptor agonist and antagonist agents on renin release (RR) and cyclic 3'5'-adenosine monophosphate (c-AMP) content of renal cortical slices from sodium-replete (SR) and sodium-deficient (SD) rats was studied in vitro. Isoproterenol (IP) doses ranging from lo-13M to E--added to slices from SR rats did not affect RR or c-AMP content. In contrast, IP doses from 10m7M to 10B3M significank ly increased RR and c-AMP content in slices from SD rats. Addition of the beta-blocker d,l propranolol (10e4M) prevented stimulation of RR and c-AMP content by lo-7M IP, but only partially inhibited the effect of a h gher IP dose (10v3M). Dopamine (DOP) doses of 10B5M and lo- 4 added to kidney slices from SD rats significantly stimulated RR, whereas c-AMP content was significantly increased only by 10m3M DOP. Addition of the DOP-receptor blocker pimozide (lo-6M) effectively prevented stimulation of RR and c-AMP content by DOP. Pimozide added alone significantly decreased RR and c-AMP content levels below those of controls. These data indicate that, 1) Sodium deficiency potentiates the RR and c-AMP responses to added IP, 2) IP and DOP exert a stimulatory effect on RR which appears to be mediated by a receptor mechanism which utilizes c-AMP and, 3) A DOP-sensitive adenylate cyclase receptor complex may participate in regulating resting RR in the SD state.


USE OF INDICATOR MUSCLES AND BONES FOR THE ESTIMATION OF BODY J. R. Luick*, R. G. White*, D. F. COMPOSITION IN REINDEER. Holleman* and T . Ringberg* (SPON: D. D. Feist). Institute of Arctic Biology, Univ. of Alaska, Fairbanks, AK 99701







MECHANICS. C. Lowe*, Dept. Physiol.NNeonatol.,





E. Sivieri*, Temple Med.

& Schl l


The relationship between pulmonary mechanics and the migration of meconium to the distal airways was determined in 10 rabbits (Av. 2.6 kg) after insufflation of a meconium-saline mixture (l-2 mg/kg). Animals were ventilated with 100% 02. Lung dysfunction was most severe 15 min postinsufflation of meconium, likely due to large airway obstruction. Arterial Pa02 fell 432 + 3 SE11 m m Hg, along with a maximum rise in PaC02 to 89 + 10 SEMmm Hg. The alveolar-arterial 02 gradient (A-a D02) and expiratory resistance (RE) increased maximally. Dynamic lung compliance (CL) fell (P0.2). In preliminary experiments, epithelial cells of necturus small intestine were impaled with microelectrodes ofype. Stable potential differences (>90 mV) between extraand intracellular media were recorded. (Supported by USPHS grant AM 12715. J. F. Garcia-Diaz partially supported by Ministerio Education y Ciencia, Spain). We thank Prof. W. Simon for the gift of-the neutral-ionophore.

EFFECT OF ADENOSINE TRIPHOSPHATE (ATP) ON PITRESSIN INDUCED MYOCARDIAL ISCHEMIA. H.H. Oei: T.C. Kopjas* and R. Weqria. St. Louis University School of Medicine, St. Louis, Missouri 63104 In the chloralose anesthetized dog, pitressin given intravenously results in a decrease of coronary blood flow and myocardial 02 consumption, and an increase in the coronary 02 arteriovenous difference resulting from a decrease in the 02 content of the coronary sinus blood. ATP given intravenously during the effect of pitressin, results in an increase in coronary blood flow, generally a further decrease in myocardial 02 consumption, and a decrease in coronary 02 arteriovenous difference resulting from a rise in the 02 content of the coronary sinus blood, then all parameters return to or toward their respective values before the administration of ATP. Thus, the administration of ATP counteracts the myocardial ischemia caused by pitressin through an increase in coronary blood flow and generally also a decrease in myocardial 02 consumption.

IS THE EARLY LARGE BIREFRINGENCE SIGNAL IN SKELETAL MUSCLE DUE TO LATENCY RELAXATION? H. Oetliker* & R.A. SchUmperli* (SPON.: K. Hermsmeyer). Dept. Physiol. University, Bern, Switzerland. The early large birefringence signal (BS) precedes any measurable changes in mechanical tension. But (BS) and latency relaxation (LR) occur in close temporal proximity (Baylor & Oetliker, J.Physiol. 264,141-162). It is therefore of interest to obtain more information about their interrelationship. Single fibres of frog M. semitendinosus or iliofibularis, placed between crossed polarizers (45'to fibre axis) were illuminated with light of 620 nm. Changes in light intensity were measured behind the 2nd polarizer during single twitches. BS and LR were recorded simultaneously with signal averaging techniques. Several procedures potentiating twitches, as caffeine (1.5mM), nitrate or tetanic stimulation (4 tet., 50Hz, 2 seach, before recording BS and LR) reduce LR to 5-30% while BS is unaffected or slightly potentiated. In double stimulus experiments (60 ms interval) in twice hypertonic Ringer LR precedes only the 1st twitch, while BS precedes both twitches. BS has maximal amplitude at sarcomere lengths (SL) around 2~, while LR is maximal around 3~ (Haugen & Sten-Knudsen, J.gen. Physiol. 68,247-266). At 3p BS is close to its minimum. These data strongly suggest that the early large birefringence signal and latency relaxation are caused by different processes. They indirectly support the hypothesis that the birefringence signal reflects a change in SR membrane potential associated with Ca-release.

ASCORBIC ACID REVERSES BRONCHOCONSTRICTION CAUSED BY METHACHOLINE AEROSOL IN NAN; INDOMETHACIN PREVENTS THIS REVERSAL. Christopher S. Ogilvy*, James D. Douglas*, Mahmood Tabatabai*, and Arthur B. DuBois. John B. Pierce Fndn. and Yale Univ., - I New Haven, CT. 06519: To determine whether ascorbic acid (aa) prevents or reverses the bronchoconstriction caused by methacholine (mech) in man, and if so, whether indomethacin (indo) blocks these effects of aa, six healthy males inhaled mech aerosol for 30 set at 25, 50, or 100 mg/ml from a D30 generator, before and an hr after ingestion of 1 g of aa. Prior to aa, the bronchoconstriction that occurred 10 min. after 100 mg/ml mech aerosol reduced specific airway conductance (SGaw) to 65% of control SE 3%, while after aa SGaw at this time was 91% SE 13%. Partial expiratory flow volume curves followed the same trend. These findings suggest that aa did not prevent the bronchoconstriction, but reversed it in about 10 min. Five subjects retested for their response to aa were given indo 50 mg orally, and their response to mech was similar to or more severe than prior to aa (10 min SG m changed from 56% to 53% of control). No significant change in SGaw or PEFV curves was noted after aa or indo, without mech challenges. This study shows that ascorbic acid partially reverses the bronchoconstriction caused by methacholine in man and suggests that ascorbic acid enhanced the production of bronchodilating prostaglandins when the bronchi were constricted by methacholine, and this effect was reversed by indomethacin.

EFFECT OF FASTIGIAL NUCLEUS STIMULATION ON PLASMA RENIN ACTIVITY. Carl A. Ohata*, Kenneth J. Dormer*, Robert D. Foreman and David C. Kern*. Department of Physiology 6 Biophysics and Department of Medicine, Univ. of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190. Previous studies in this laboratory have demonstrated a sustained pressor response (FPR) during stimulation of the fastigial nucleus (FN). However, the extent of renal involvement associated with the FPR is unknown. Thus changes in plasma renin activity (PRA) were monitored during stimulation of the FN in the cerebellum of dogs which were anesthetized with chloralose. The magnitude of electrical stimulation of either FN was varied from various sub-pressor levels to the minimal level necessary to elicit a FPR. For the duration of the stimulation period (lo-15 minutes), mean blood pressure (BP) was unchanged in the former condition whereas a sustained increase in BP of about 10 mm Hg occurred during FPR stimulation. Differences in PRA were also related to the stimulus parameters. At sub-pressor stimulus levels, PRA was either unchanged or increased relative to the pre-stimulus control level of PRA. At the increased FPR stimulus levels, PRA was always increased. The level of PRA was increased after three minutes of stimulation and oscillated from the higher to control levels for the remainder of the stimulation period. The results of this study are consistent with the view that FN stimulation activates sympathetic efferent pathways which may increase both mean arterial pressure and plasma renin activity. (Supported by NIH Grants HL 05670, HL 22732 and HL 19279.)

CONSTRUCTION OF A THREE DIMENSIONAL MODEL OF THE BRAIN AND SPINAL CORD AS AN AID IN TEACHING NEUROANATOMY AND THE ORGANIZATION OF THE NERVOUS SYSTEM, D. A. Olewine, Department of Biology, Georgia Southern College, Statesboro, GA 30458. The purpose of the model is to give students a concept of the nervous system and a three dimensional appreciation of -the 1ocati on and arrangement of specific nerve tracts. The of four spina 1 segments, a lower and upper model cons ists medullary section, cerebellum, a-coronal section through the cerebrum showing relations of thalamus and corpus straitum to each cerebral hemisphere, and a sagittal section of the hypothalamus and pituitary. Lateral and medial views of each The origins of IX and cerebral hemisphere are also included. X cranial nerves and the origins of the sympathetic nerves are clearly seen. The various nerve inputs to the cerebellum and its relation to the extra pyramidal system are also shownSpecific nerve pathways are represented by strands of yarn with blue shades indicating sensory tracts and red shades sigIn assemblying the model the student nifying motor tracts. begins at a specific sensory receptor or cell body of a motor nerve and traces with the yarn the pathway of the nerve impulse from its origin to its final destination.

24 HOUR URINARY STEROID EXCRETION PATTERN IN YOUNG MALES WITH TYPE A AND TYPE B BEHAVIOR PATTERNS. D. A. Olewine, G. Thomas* cl. T. Simpson*, and C. G.' Hames*. Georgia Southern College, Statesboro, GA 30458 and Evans County Health Department, zlaxton, GA 30417. From a group of 50 young males aged 24.9 + 0.5 years (X + S.E.) given the Jenkins Activity Scale, the 10 subjects with the highest degree of coronary prone behavioral pattern (Type 4) and the 10 subjects with the highest degree of coronary resistant behavioral pattern were selected for a study of urine steroid excretion patterns, Scores on the Jenkins Activity Gcale were: Type A's = + 9.4 2 0.7 vs. Type B's = - 8.7 + 1.3; While the subjects maintained their normal daily P = 45 min) with radiolabelled ligand. Zero degree binding is inhibitable with mannan as well as mannoseor N-acetylglucos amine-termi .nal glycoproteins or with EGTA. Surface-bound ligand can be completely remo ved by treatment of cells at zero de grees with t rYPs in and EGTA. -Using trvpsin/EGTA releas able radioac tivi tY as an index of surface bo&hd material, it can be shown that internalization of zerodegree-bound ligand is very rapid (O.O05). s/CO2 was slightly higher (9%) during occlusion and this was associated vith a significant reduction in PvCO2, PETCO , and PaC02. %9.5 k/min VE for,a given VC02 (VE/VC02) was 45.3 cf. per (p>O.O05). Following litre VCO in OE and NOE respectively release oi occlusion, previously trapped CO2 reached the lungs in 5 sets. However, VE fell for 12 sets and only then started to rise in parallel with an increase in VC02. PETCO2 was unchanged for 5 sets but after 12 sets rose to an.asymptote similar to that found in NOE. At the same-time VE/VC02 returned to normal values (Q29 l/min per litre VCO2). Hence although the ventilatory drive produced by occlusion may have been neurally mediated, once the normal balance between PKO2, (~12 sets after the PETCO 9 and PaCO had been re-established end o P occlusion to return to a level related to f VE appeared CO2 production. (Supported by the MRC of Canada).

THE EFFECT OF AN ACUTE ETHANOL DOSE ON ACID-BASE AND FLUID AND ELECTROLYTE BALANCE IN THE ACIDOTIC DOG. F3.Q. Sargent, J.R. Simpson*, and J.D. Beard*. Dept. of Physiol.,Univ. of Tenn., Memphis, Tenn. 38163. Acidosis was induced in 10 male mongrel dogs by feeding 10 meq/kg of NH4Cl in the 4 p.m. food ration. ETOH (2 g/kg-25% v/v) or H20 was given by oral intubation at 8 a.m. Urine volumes and H20 intakes were measured from O-3, 3-8, and 8-24 hrs post administration (PA). Jugular blood was obtained before the acid load, before the ETOH or H20 dose, and at 1,2,3,5,7 and 24 hrs PA. The acid load produced sig. reductions in blood pH, plasma K (PK), and In this acidotic the ETOH or H20 dose. 'H 0 before mo $1e , the ETOH dose produced a transient diuresis, O-3 hrs, and an increase in UNa*V from O-3 hrs. During 3-8 hrs fluid intake was sig. elevated in the ETOH group. From 8-24 hrs, there was a sig. reduction in urinary Na, K, and Cl excretion in the ETOH group and water intake was again elevated. The ETOH dose produced a sig. decrement in PK and increments . The results suggest that In PNat p and 'HCOa= prior aci 8 2::s did not alter the effect of an acute ETOH dose on acid-base and fluid-electrolyte balance Supported by USPHS Grant AA 02670 and the State of Tennessee, Department of Mental Health.

RECOVERY RATE OF THE CARDIOVASCULAR SYSTEM FROM SHORT-TERM ANESTHESIA WITH HALOTHANE IN RABBITS. Madeline Sartick*, Mary Eldridge*, J. Alan Johnson, Kenneth D. Kurt*, Wayne L. Fowler, Jr.*, and Charles G. Payne*. Harry S Truman Mem. V.A. Hosp. and Dept. of Physiology, Univ. of Missouri, Columbia, Mo.65201 This study examined the cardiovascular effects of shortterm anesthesia with halothane, and the recovery rate folir>wing cessation of halothane in rabbits. Measurements were made of mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) in 8 conscious rabbits, and were repeated after 15 min. of halothane (in N20 & 02); measurements were again obtained at 15, 30, 60, and 210 min. after stopping the anesthesia. The results (means +SEM) were: halo-thane

~control (mm Hg)

co (ml/min


HR (beats/min)


= PcO.05

-15 min







210 min ______ 90 24

191 218

144** 218

190 219

197 +20

188 219

190 212

253 216

339* +24

339** +14

326* 217

302* 215

279** +14



= PcO.01

This study ind icates that in rabbits rapidly af ter short-term anesthesia

NEUROTRANSMITTER REGULATION OF ARGININE VASOTOCIN RELEASE FROM RAT PINEAL GLANDS IN VITRO. J. L. Sartin", B. C. Bruotfi, and R. J. Orts. Dept. of Physiological Sciences, Oklahoma State University, Stillwater, OK 74074. This investigation was conducted to investigate the effects of neurotransmitters on in vitro arginine vasotocin (AVT) secretion. Rat pineal glands were pre-incubated for 30 min. and subsequently incubated for 8 hours. Pineals were treated with 10-8 M and 10-8 M norepinephrine (NE), dopamine (DA), serotonin (5-HT), acetylcholine (Ach), and taurine (Tau). The incubation media were assayed for AVT by radioimmunoassay. NE was found to have no effect on AVT release at either concentration. Both 10B6 M DA and 10-8 M 5-HT released more AVT than the appropriate controls but the differences were not significant. Ach released more AVT than controls at both 10-8 M Ach (p c.08) and at 10B6 M Ach (pncrease in CAMP was detected. Present results thus indicate that 5-HT

acts latory

on renal effects

CAMP only in are in Gl.

CTX and






TEMPERATURE REGULATION IN THE SQUIRREL MONKEY IN HIGH PRESSURE HELIUM/OXYGEN ATMOSPHERES. M. E. Sheehan, J. S. Jones*, D. L. Nesbitt*, M. C. Rich*, and R. W. Brauer. Institute of Marine Biomedical Research, UNC-Wilmington, 7205 Wrightsville Ave., Wilmington, N. C. 28403. Squirrel monkeys implanted with perfusion thermodes in the preoptic anterior hypothalamus (POAH) were subJected to pressures up to 50 atm in He/O.5 atm 0,. At each pxessure ambient temperature was progressively incrgased from 25" to the point of massive vasodilation. was used to define upper and

EFFECT OF AMBIENT PRESSURE, GAS DENSITY AND HYPEROXIA ON THE HEART RATE OF THE RAT. K. Shida*, B. Respicio*, and Y.C. Lin. Univ. of Hawaii John A. Burns Sch. of Med., Honolulu, HI 96822 By means of subcutaneous ECG leads, the heart rate of unanesthetized rats was recorded under 10 separate environmental conditions. The purpose of this study was to determine to what extent ambient pressure and hyperoxia cons t3a s density tribute to the bradycardia associated with hyperbaric exposure. Gas density was varied from 0.34 to 11.45 g/L by using either nitrogen-02 or helium-02 mixtures, oxygen partial pressure ranged from 140 to 1590 mmHg, and the ambient pressures applied were 1, 3, and 10 atmospheres. Values obtained during compression were averaged over 30 minutes and the changes were compared to values at 1 ATA air. Significant changes in heart rate were not observed in rats in normoxic nitrogen or normoxic helium at the elevated ambient pressures. However, significant decreases in heart rate occurred in hyperoxic nitrogen at 3 ATA (60.01) and 10 ATA (pcO.01). Greater bradycardia was observed in 10 ATA than in 3 ATA hyperoxic nitrogen (60.05). The heart rate in hyperoxic nitrogen and in hyperoxic helium at 10 ATA was essentially the same (~9.4) indicating that increased gas density played no significant role in the hyperbaric bradycardia. It appears that hyperoxia, of the variables considered, is the most important factor. (Supported by Sea Grant 04-7-158-44129,HP/R2).


lower critical temperatures. The euthermal interval between these points narrowed from 7' C at 5 atm to lo at 30 atm. Within this "arrow euthermal range, rectal temperatures average 0.75" C lower in high pressure He/O, than in the same animal in air at 1 atm. The decrease in euehermal interval is paralleled by a decrease of POAH temperature displacement required to elicit a metabolic response, suggesting an increase in hypothalamic responsiveness with increased pressures. 0, increases 200% with increasing pressure up to a maximum nearL 30 atm; thereaf'ter, it decreases again, qualitatively as in the mouse. The high metabolic rates cannot be reversed by increasing chamber temperature to the limits of tolerance, or by increasing POAH temperatures to 41.5' C. Implications of these results will be discussed. (Supported jointly by ONR and the Naval Research and Development Command - ONR Res. Contr. 1?00o-14-75-~-o468.)

THE IMPORTANCE OF ABDOMINAL PRESSURE FOR BLOOD VOLUME DISTRIBUTION AND CENTRAL VENOUS PRESSURE CHANGE DURING HEAD-DOWN TILT. M. Shimizu*, D.N. Ghista* and H. Sandler. Biomedical Research Division, NASA, Ames Res. Ctr., Moffett Field, CA 94035. The drop of the central venous pressure (CVP) during head-up tilt is explained clearly by the mechanics of a simple blood column model, however, the slight drop of CVP during head-down tilt to -Gz stress is contrary to such prediction and its mechanism has remained unsolved. In order to understand this latter finding, a mechanical model has been deve loped simulating the inferior vena cava. The model is similar to a Starling Resistor and capable of compressing the vena cava in the region between the diaphragm and a pelvic floor (by a fluid column) to simulate hydrostatic pressure due to the splanchnic organs (abdominal pressure) . The static pressure distribution along the vena cava (simulated by dialyzer and/or rubber tubes) has been measured for various conditions. Results indicate: (1) both in r ecumbent and head-down ti It positions , the static pressure in the tube changes abrup tly near the site of the diaphragm. This has been observed in the human or dog inferior vena cava in recumbent and head-down t ilt positions. Observed ve nous pr 'essure changes are governed by the abdominal pressure; maintains the bl .ood volume pooled pressure (2> th iS abdominal in the abdominal v enous vessels in the head-down tilt position at the same level as observed in the recumbent position; and, effec ts of the abdominal pressure during head-down (3) these til ting pr event CVP from rising above the level recorded in the recumbent position.

MECHANISMS OF REFLEX CONTROL OF THE CARDIAC CONTRACTILITY BY CAROTID SINUS BARORECEPTORS. T. Shimizu* and V.S. Bishop. The Univ. of Tex. Hlth. Sci. Ctr., San Antonio, Tex. 78284 Carotid sinus baroreflex (CSB) has been known to affect both sympathetic discharge to the heart and catecholamine secretion from the adrenal glands. The present study was performed to quantititively evaluate the effects of CSB on cardiac contractility via these two different mechanisms in anesthetized cats. With aortic nerves cut, changes in CSB were produced either by bilateral carotid occlusion (CO) or by changing intrasinus pressure in the isolated carotid sinus (ISP). Left ventricular peak dP/dt was used as an index of the contractile state of the heart. To exclude the effect of changes in blood pressure (BP) on s/dt, AdP/dt/ABP was determined during aortic occlusion and was subtracted from a net change in dP/dt either with CO or ISP change. During control, CO produced increase in dP/dt (1210 rmnHg set). Change in ISP from 150 to 50 mmHg also increased dP/dt (1580 mml-lg). After bilateral surgical stellectomy, these changes decreased to 790 and 1110 mmBg, respectively. Time to peak response was cignificantly delayed from 21.1 to 52.3 sec. Subsequent adrenectomy or administration of propranolol greatly attenuated for the reflex changes in dP/dt. These results indicate that, besides the cardiac sympathetics, catecholamine secretion from adrenal medullae is a major factor contributing to the reflex control of cardiac contractility by CSB. (Supported by NIH grant HL-12415 and AFOSR #73-2525).



BLOOD FLOW (SPON: D.G. Reynolds). University of Iowa, Iowa City, Iowa 52242. Recently we demonstrated that Metiamide prevented stressinduced gastric erosions in dogs. In order to clarify Metiamide's role in H+ secretion and mucosal blood flow (MBF) in shock, the following experiments were performed. In five conscious dogs H+ secretion and MBF were measured under control conditions and 30 min after hemorrhagic shock (HS) (MBP = 50 In five other dogs MBF and acid secretion were measured under control conditions 30 min after 300 mg Metiamide IV, 30 and 90 min after shock. 15~ labeled microspheres were used for MBF measurement. The results are expressed as ml/min X 1OOg of tissue for BF and mean mEq/hr for H+ secretion. mHg)

FMBF AMBF H+ * ~~0.05

9Ok16 12OklO 1.981t.16 compared

30 Min - Shock 21*k+3 2O*k4 0.12*‘+.02

Baseline m 67klO 74+7 2.15~17

45 Min postinj. 76+23 55k7 0.4*

30 Min Shock

90 Min Shock

15*&l 52+20 0.12*

14*k2 107k27 0.11”

80% of

zero P.







as urate.



frog, terrestrial

V. H. of

excretes anurans



B. boreas,





ml kg-i




cretion reflects slightly effective

to control

These results indicate that: 1) hemorrhagic shock nificant reduction of acid secretion and mucosal 2) Metiamide significantly reduces H+ secretion. with Metiamide does not improve blood flow to the shock. It appears that Metiamide prevents stress by decreasing H+ secretion rather than affecting


produce urea which they do not excrete when they are deprived of water. We investigated the differences in renal function underlying the unusual excretory capacities of P. sauvagei. Glomerular filtration rates (GFR) were measured-in P. sauvagei in water and when deprived of water, except that in-food, for up to 30 days. For comparison a toad (Bufo boreas) was studied in water and during water deprivation.water both species produced 30-50 ml urine kg-l hr-1 and resorbed only 30-50% of the filtrate. With water deprivation, GFR rapidly approached




Shoemaker and P. E. Bickler.* Dept. of Biology, California, RiTerside, CA 92521. Phyllomedusa sauvagei, a xeric adapted tree

despite reductions in urine production of up to During water deprivation in P. sauvagei, urate exwas between 250-300 pmoles kg-l-hr-1 and 90% of this net tubular secretion. Urate clearances were only less than those of para-amino hippurate, indicating removal of urate from the peritubular circulation.








98-99%, and 85% of the potassium was resorbed. At low rates of urine product ion, urine to plasma (U/P) ratios for inulin in bladder urine were 20-100 whereas those for ureteral urine were ca. 10. The urinary bladder also functions as a water reserve during dehydration. (Supported by grant DEB 75-06922 from NSF. )

causes sigblood flow & Pretreatment fundus after ulceration blood flow.






VOLTAGE C-LAMP ANALYSIS OF MEMBRANE CURRENTS AT SUBTHRESHOLD POTENTIALS IN EMBRYONIC HEART CELL AGGREGATES. -A.Shrier*,J.R. Clay*, and R.L.DeHaan, Anatomy Dept., Emory Univ., Atlanta,GA 30322. (Sup. by Can.Hrt. Fndn. and NIH HL16567 and HL05346.) We have recorded membrane currents in the -45 to -90 mV range from small (D s 150 pm) spheroidal aggregates of 7 day old chick embryonic ventricular heart cell aggregates using the two microe&ectrode voltage clamp technique. Tetrodotoxin was added (lo-' g/ml) to suppress spontaneous beating which occurs in normal culture conditions (K =1.3 ti4, T=36.5OC). is shown by voltage The resting potential (E-) is -50 mV which clamp analysis to be the=result of a time dependent current background activated between -5 5 and -45 mV and an inward time dependent current exists between -80 current. A second and -65 mV which inwardly rectifies. The time course of membrane currents in both regions can be described by a single E to exponential function. Increasing K to 2.5 mM changes -70 mV. In this condition the memb:ane often spontaneougly oscillates in a pattern described previously (DeHaan and DeFelice, 1978, Theo. Chem. 4, ed. H. Eyring, p. 181). In .on exvoltage clamp the steady state current voltage relati points at -70 and -50 mV hibits positive sl .ope zero-current This of negative s lope conductance in between. with a region result sugges ts that small fluctuations in membrane cur rent may be partly responsible for the unstable character of the E= -70 mV state, s 3rice the membrane slope resistance is infinity lgrge (50-100 KQ*cm ) at E = -70 rn\ and approaches the negative slope region. at the hyperpolarizing end'of

K. Sagawa. The Johns Hopkins Medical School, Baltimore, Md. In order to quantify the effect of epinephrine on the baroreceptor reflex control of vascular capacity and resistance, C we have simultaneously measured total systemic compliance, T' arterial compliance, Ca, changes in "unstressed vascular volumell, AVo, and resistance, R, in 9 dogs whose carotid sinus es were isolated and cardiac output fixed by a perfusion pump. ISP, of 50, 125 and 200 mm Hg and At each intrasinus pressure, without epinephrine infusion C increased from 1.00, and 1.10 and 1.22 ml/mmHg/kg, whereas C$ showed no difference and averR decreased from 1.45 to aged .084 ml/mmHg/kg for all ISP's. .88 and .57 mmHg/ml/min/kg. AVo for changes in ISP from 50 to 125 and from 125 to 200 mmHg were 7.32 and 5.03 ml/kg. When epinephrine was given at a constant rate of 1.2 ug/min/kg at fixed ISP of 125 mmHg, arterial pressure rose 69.1 mmHg, AVo was 8.02 ml/kg and R increased from .89 to 1.54, a change of .65 mmHg/ml/min/kg. At the same infusion rate and at eachISP of 50, 125 and 200 mmHg C , Ca and R were remeasured. In contrast CT showed no increazes and was .92, .94 and .92 ml/mmHg/ kg while Ca measured ,081 ml/mmHg/kg. R decreased from 1.71, AVo for ISP changes from 50 to 1.46 and 1.19 mmHg/ml/min/kg. 125 and 125 to 200 mmHg were 1.78 and 1.30 ml/kg. The data

indicate of the cation

that epinephrine greatly attenuates vascular properties by mechanism other of the receptor characteristics. (Supported by Grant HL-19039)

the reflexcontrol than modifi-

INCUBATED Arthur W. Siebens* and Floyd M. Kregenow. NIH, Bethesda, Md. 20014. Red blood cells from several animals, notably the duck, return toward their normal isotonic volume af ter first shrinking 0 r swelling in anisot onic media. They utilize Ouabaininsensitive cation transport mechanisms to alter total salt content; shifts in cell,H 0 change volume. Amphiuma red cells were studied since their z arge size should permit future study of volume regulation via micropuncture. Cells enlarged 30% in hypotonic media shrink by losing K and H 0 for 6-8 hrs before stabilizing at a new volume, slightly 1arger than normal. Na content remains unchanged. Cells shrunken 20% in hypertonic media gain Na and enlarge to a stable volume in l-3 hrs. Na uptake results from a more than 30-fold increase in Na influx and is unaffected by the removal of medium K or Ca. Amiloride completely inhibits the increase in Na i3flux, preventing enlargement. 50% inhibition occurs at 10 M Amiloride. Ouabain, though ef feet ive in blocking the pump, does not affect the changes in either total cation content or volume seen in these responses to hypoor hypertonicity. Although the hypotonic response is similar to that seen in duck red the response to hypertonicity differs - Amphiuma cells cells, require only extracellular Na whereas duck cells require both Na and K. Inhibition by Amiloride suggests a possible similarity between the Na transport mechanism induced in Amphiuma cells by hyper toni city and that at the mucosal border of some epithelia.

PINEAL DEVEIL)PMENT AND EFFECT OF VITAMIN A DEPRIVATION ON PINEAL PHOTORECEPTORS. J. Silver. Dept. of Zoology, University of Texas, Austin, Texas. 78712. The photoreceptive and secretary ability of the avian pineal and some cytoplasmic organelles are still in doubt. Newly hatched chickens have immature pineals. Fenestrated capillaries, nerve fibers and an increased vasculature, all of which are important for secretion, appear during the first week posthatch. Synaptic ribbons and membranous whorls are rare and simple during the first week posthatch. These structures increase in number and complexity during the first month posthatch. The photoreceptive apparatus of the pineal is believed to utilize a photopigment derived from vitamin A. The pineals of newly hatched chickens raised for up to four weeks on a vitamin A free diet, contained all of the normal cellular structures but no membranous whorls. Chickens deficient, in vitamin A, then supplemented with vitamin A, contained pineals with well developed membranous whorls. Vitamin A may be necessary for the integrity and/or formation of pineal membranous whorls. The avian pineal may be a functional photoreceptor.

MODELLING OF THE VERTEBRATE RETINA. Robert Siminoff, BRI, UCLA Center for the Health Sciences, Los Angeles, CA 90024. A detailed model of the generalized vertebrate retina will be presented. The basic organization of photoreceptors (PC) is a hexagon of 7 like-PCs. The bipolar cells (BC) are formed into center-surround antagonistic fields. The center field is formed by direct inputs from a hexagon of PCs while the surround field is formed by inputs from 6 horizontal cells (HC), each of which receives direct inputs from a hexagon of PCs. Electrical coupling between like-PCs and stray light lead to filling up of the receptive field, the proper weighted inputs and overlap of the center and surround fields. Negative feedback via L-HCs to PCs produces increased contrast between colors and regions of the fields. Models of both the Chromaticity (C) and Luminosity (L) systems are presented and the roles of the various types of HCs are shown in producing the receptive field organizations of L- and C- types of BCs. By assuming linearity it is possible to derive mathematical expressions for the polarity changes produced in the various retinal elements as a result of hyperpolarization of a PC. Manipulation of the gains of the various synapses involved produces any known type of receptive field organization. The model of the BC acts as the building block for all other levels of the visual system since the annular organization is a basic feature. The cones are organized into a trichromatic system but at the level of the BC, the system is organized into opponent color coding for the C-channel.

EFFECT OF ASSISTED VENTILATION (IIPPB) ON AIRWAY OCCLUSION PRESSURE (Ploo) AND INSPIRATORY MUSCLE EMG: ROLE OF VAGAL UCLA AFFERENTs. D.H. Simmons*, C.S.H. Tan, and H. Green. School of Medicine, Los Angeles, California 90024. Sixteen healthy dogs were deeply anesthetized with barbiturates. In 9 experiments, 30 min periods of spontaneous breath ing were alternated with 30 min periods of IPPB, applying peak airway pressures (PAW) of 5, 10, 15 and 20 cm H20 in random Pa02 was maintained ,100 mmHg. We measured PaC02 and order. Ploo at the end of each period in all experiments, and diaIn 4 similar experiments phragm electromyogram (EMG .) in 4. (PAW 20 cm H20) externalizga vagal loops were cooled from 38O to 8', 6', 4', O°C and bilateral vagotomy was also performed. In 6 experiments external intercostal electromyogram (EMG .) was measured at vagal loop temperatures of 38O, O" and aft&r during IPPB at all vagotomy. Mean Ploo and EMG . decreased peak pressures. (At PAW 20,DiP1~~=-56%, AEMG .=-58%). Decreases correlated well (r=O.76; P and for shorter time periods (presteady statePSS.) Results: (i), 16 SS determinations on 9 subjects S=4.95'2.05 g N/kg/day. (ii). 6 SS values on one subject, 3.6iO.5 g N/kg/day. (iii) PSS. The shorter the study time, the larger S. The data fitted the regression equation S=6.2-0.22 x time (hr.) We suggest that this apparent time dependency of S is real and what is being measured is a contribution to the time weighted value for S which reflects fast turning over proteins. These cannot be detected in a true isotopic steady state method. (Supported by NIH grant #AM 16658.)

EFFECT OF METHYLPREDNISOLONE ON INTESTINAL MESENTERIC VASCULAR RESPONSES OF HEMORRHAGED AND NONHEMORRHAQZD RATS. W.J. Stekiel, D.R. Harder, and P-J J.H. Lombard Dept. of Physiol., Med. Coll. Wisconsin, Milwaukee, WI 53233 To evaluate potential mechanisms of the protective e ffect of glucocorticoids in low flow states, diameters of sma 11 mesenteric arteries and veins were measured directly in hemorrhaged and nonhemorrhaged rats anesthetized with pentobarbital and pretreated with methylprednisolone (MP) (30 mg/ kg, i.v.) or its diluent. Hemorrhaged rats were maintained at a constant mean arterial pre ssure of 35 mm Hg until 30% uptake of maximum bled volume. The functional state of the adrenergic neuromuscular junction was assessed by measuring the vasocon strictor response to periva scular nerve stimulation. In nonhemorrhaged c ontrols, Ml? produced no significant change in vessel diameters or in v ,ascular responses to stimulation stress, steroid t reated rat S . During hypotensive tended to have greater bleedout vol umes than nontreated aniThe promals and reclaimed shed blood at aslower rate. tective effect of ME, on the adrenergic neuroeffector junction (Stekiel 20:91) does not potentiate --et al. Physiologist splanchnic vasoconstriction during the hypovolemic period. During this time, vessel diameters of steroid treated rats remained significantly greater than nontreated controls and the response to stimulation decreased significantly in both groups. These data suggest that MP may maintain tissue perfusion in low flow states by a mechanism unrelated to direct vasodilation or a-receptor blockade.(Support: NIH VGM23594).

PERIPHERAL UTILIZATION OF GLUCOSE IN RATS AND CHICKENS AFTER ALLOXAN (AL) AES) STREPTOZOTOCIN (SZ) AIMNISTRATION. William .A. Stellenwkrf” and Robert L. Hazelwood. University of---Guston, Houston, Texas 77004. Intravenous glucose tolerance tests (GTT) were administered to adult rats and chickens on day ‘0’ and on days 5, 10 and 1S following injection of AL or SZ at doses established to be diabetogenic in maJTPnals. Also, the effect of pancreatectomy (99%) on previously SZ-injected chickens was evaluated by use of GTT’. Plasma immunoreactive insulin (IRI) , glucose and electrolytes were measured. Results obtained indicate that at 5 days both AL and SZ caused expected qualitative and quantitative disturbances in the GTT and in basal plasma IRI and glucose levels of rats. Chickens were impervious to AL at a dose 3 times the diabetogenic dose in rats. Glucose uptake in SZ-chickens also was unaffected (p>.OS) even though glucoseinduced insulin secretion was markedly reduced (pc.01) on each day tested. The SZ-depancreatized chicken exhibited a glucose-induced insulin secretion similar to SZ-treatment alone; however, an impaired utilization of the injected glucose load was observed (pc.01). Pancreatic tissue IRI concentration was generally reduced with SZ. We conclude that insulin is of secondary importance in regulation of glucose metabolism in the chicken.

CHANGES IN CARDIAC OUTPUT AND PLASMA VOLUME DURING SODIUM DEPLETION IN CONSCIOUS DOGS. G. A. Stephens*, J. 0. Davis, R. H. Freeman, J. M. DeForrest, A. A. Seymour*, B. P. Rowe*, G. M. Williams*. Department of, Physiology, University of Missouri School of Medicine, Columbia, MO 65212. Hemodynamic, fluid and electrolyte changes were studied during sodium depletion and repletion in six conscious dogs. Blood pressure (BP), plasma renin activity (PRA), heart rate cardiac output (CO), stroke volume (SV) and plasma volume (HR), (PV) were determined on three separate days in sodium replete, conscious dogs. Similarly, three daily measurements were made after the dogs were sodium depleted and again after sodium reDuring sodium depletion,HR increased from 71, 73 and pletion. 77 to 89, 90 and 94 beats/min (~~0.05 for each value). CO fell from 2.30, 2.29 and 2.37 L/min to 1.85, 1.90 and 1.87 L/min (~~0.05 for each value). SV decreased from 33.0, 32.7and 32.0 ml to 21.3, 22.3 and 21:5 ml (~~0.01 for each value). Peripheral resistance (PR) increased from 42.5, 41.8 and 40.3 to 50.2, 48.9 and 48.4 mm Hg (L/min)-1 (~~0.05, 0.05, 0.1). BP was unchanged. PV decreased from 1201, 1193 and 1224 ml to 1083 ml (~~0.05) during the first sodium deplete measurement. PRA increased from 0.73, 0.92 and 0.85 to 7.58, 7.10 and 7.59 ng AI/ml/hr. During the 8 days of sodium depletion, water intake was elevated on 6 days, urine volume was elevated on 5 days and water balance was positive on 3 days. Wi th sodium repletion all functions returned to control levels . The results demonstrate that sodium depletion produced signifi cant decreases in CO and PV with BP maintained by increased PR.


by University






RENAL EXCRETION OF UREA IN THE SALAMANDER, AMBYSTOMA TIGRINUM. -----7D. F. Stiffler, C. T. Hawk* and B. C. McCusker* Blol. --- Sci. __-------_----------A------s--m-' Dept., Callf. State Polytechnic Univ., Pomona, CA 91768. Excretion of urea was assessed in larvae and adults by comparing urea clearance (Cu) to inulin clearance (Gin). Cu/Cin>l indicates net urea secretion; Cu/Cin25% in ew Ss and ratio After SC terb, VmaxSO increased _>O.lO in oi?Yy one subj$Ct. increased >25% in 10 Ss and ratio Vmaxsg increased >O.lO SG inaY Ss. These findings are consistent with the assumed action of aer terb mainly on large airways and of SC terb on both

ratio small




Vmax5O by _BO.10 airways.




may be a useful

that index


an increase dilatation

in of

EFFECTS OF BARIUM AND CALCIUM ON NOREPINEPHRINE (NE)- AND POTASSIUM (K+>- INDUCED CONTRACTIONS OF ISOLATED MESENTERIC ARTERIES. M. Taxer* and G. Ross, UCLA School of Medicine, Los Angeles, Ca. 90024. The abilities of calcium (Ca*> and barium (Ba*) to sustain contractions in isolated cat mesenteric arterial segments were studied under three conditions: 1) in Caft-free --in vitro Krebs solution (PSS), 2) in Ca*-free depolarizing solution containing 1OOmM KC1 (DPSS), and 3) in the presence of the potassium-conductance blockers tetraethylammonium (TEA) or 4-aminopyridine (4AP). In DPSS the contractions induced by 0.25mM and O.&M Ca* were significantly greater (Pc.01) than those produced by corresponding Ba* concentrations; but the responses to 0.05 and 1.6mM Ca* and Ba* were similar. Barium addition to PSS produced a dose-dependent contraction over the range 0.25mM-1.6mM. NE dose response curves were similar with 0.05 and 0.25mM Ca* or Ba*; but at 0.8 and 1.6mM, the NE threshold dose and the maximum NE contraction were lower for Ba* than for Ca*. Tetraethylammonium and 4AP augmented NE responses in Ca*-containing but not in Ba*-containing PSS. It is concluded that in addition to its known action as a potassium-conductance blocker, Ba* can substitute for Ca* in E-C coupling in mesenteric arterial smooth muscle. (Supported by grant HL-18199 from NHLBI.)

PRE AND POST CAPILLARY RESISTANCES IN ISOLATED DOG LUNGS DURING ALVEOLAR HYPOXIA. A. E. Taylor, R. E. Parker, J. Parker, and D. N. Granqer, Dept. of Physiology, Univ. of South Alabama School of Medicine, Mobile, Alabama 36688. Pre and post capillary resistances (Ra and R,, respectively) were measured in isolated dog lung using isogravimetric procedures. Control isogravimetric capillary pressures (Pci) were measured in 8 isolated lungs, ventilated with 95% 02 and 5% CO2 in a Zone III condition (Pa>Pv>PaL). From this measurement, Ra and Rv were estimated using the slope of the line relating total blood flow to the isogravimetric arterial and venous pressures. The lungs were then ventilated with 95% N2 and 5% CO2 for 30 minutes and Pci was again estimated for each isolated lung. Ra increased 220 f 25 (SEM) % above control values whereas R, was relatively unchanged values) and the total resis(100 f 15% of control tance changed by 198 f 25%. The increase in total pulmonary resistance observed with alveolar hypoxia appears to be due to changes in only pre-capillary resistance without any observable effect on venous resistance. Supported by NHLBI Grant 22549.

DIURNAL CHANGES IN SERUM CORTISOL AND GLUCOSE IN FUNDULUS HETEROCLITUS AND GOLDFISH. Ma= --CARASSIUS AURATUS. Taylor, Nancy 3. Brown* and Glenn J. Leach. School of Life and Health Sciences, University of Delaware, Newark, De.19711 Serum cortisol (radioimnunbassay) and glucose (glucoseoxidase method) were measured in samples taken every 2 hours for 84 hours in E. heteroclitus and 48 hours in goldfish, in an attempt to document circadian periodicities. In both species,. peaks in cortisol averaging 6-12 pg/lOOml were superimposed on baseline levels of less than 2 US/ml. These peaks were quite pronounced in Fundulus, occurring once or twice a day independent of photoperiod. Autocovariance and Power spectrum analysis of these data detected no periodicitv in cortisol levels.Serum glucose levels in Funduius were variable with means of 55-90 uq, but no time related trend. In the goldfish, serum glucose-did vary in an apparently regular fashion, but again, time series analysis identified no circadian or shorter periodicity. Thus, it is concluded that under our experimental conditions, neither cortisol nor glucose levels in serum vary diurnally in the two species tested. The levels of these parameter, especially cortisol, vary in a pattern suggestive of pulsatile release which in a single 24 hour period bears a misleading resemblence to a circadian periodicity.

DIFFUSIVE RESPIRATORY ALKALOSIS AND METABOLIC CHANGES INDUCED IN THE CHICK EMBRYO BY A HELIUM ATMOSPHERE. H. Tazawa*, A. Ar*, A. H. J. Visschedijk*, H. Rahn, and J. Piiper. Abt. Physiol. Max-Planck-Institut exp. Med., G&ti.ngen, F. R. G. , and Dept. Physiol. , State Univ. of New York at Buffalo, Buffalo, N. Y. 14214 The arterialized blood of the chorioallantoic vein of the chick embryo on day 16 has a PGo, of 34 torr and a pH of 7.57. When the ambient N, in air over the egg is exchanged for He, a prompt and profound diffusive respiratory alkalosis is induced. Within one hour the air cell and blood PCO, fall to half the normal value. The blood pH rises to 7.74 and remains there for the length of exposure (two hours), while the metabolic rate increases by 13%. The opposite effect, a diffusive respiratory acidosis, is induced by placing the egg in an SF6 -0, atmosphere in which the arterialized blood PCOz nearly doubles (62 torr), the blood pH falls to 7.42, and metabolism is reduced by 13%. These responses are initiated by changes in the diffusivity of CO* which alter the gas conductance of CO, across the gas filled pores of the egg shell. The CO, conductance, relative to its normal value in air, increases 2.4 times in He and is reduced to one-half in SF6 (Ar et al., The Physiologist 21, 1978).


WERCISBTRAINING AND CARDIACVASCULARIZ)rTION. G,D3har~ and C.T.UaRner? School of Life Sciences. Unlvemlty of Nebraska. Lincoln, Nebr, 68588 Hale albino rats were trained on a motorized t&ml11 for 8 weeks, using 8 training regimens which varied In severity from 0.7 mph-3 days/week-JO mln/day to 1.0 mph-5 days/wk60 tin/day. At the end of the 8 weok training period the animals were anesthetized and Pellksn Ink was Infused retrograde through the aorta, co-es and capillaries of the heart. The hearta uere sectioned, stained and examined for the number of caplllarlss/mm2 and the capillary/muscle fiber (C/F) ratios. Six of the eight exercise groups had capillary densities significantly lower than the density of the sedentsry cantrol group 0f 3022 cap/md. LIkewIse, five of the exercise groups hsd slgnlflcaMAy lower Cb ratios than the sedentary group rcrtlo of 1.077. These resulti indicate that exercise training does not stimulate caldlac capillary prollferatlono The lower capillary density In the trained animals could be produced by fiber hypertrophy which would push the capillaries farther apart. These findings are In agreement with Hakklla (1955) and Frank (1950) but disagree with Bell and Rasmussen (1974) who found an Increase In capillary density with exemlse. The lower C/p ratios of the trained rats In this study are mars difficult to explain as other studies have reported an Increased C/k ratio with tralnlng. One serious problem with such data Is the difficulty In ldentlflcatlon of lndlvldusl cardiac fibers due to their branching and anastomoslso

Pituitary Response to TRH and LHRH in Spontaneously Hypertensive Rats. G.E. Tempel, J.R. Sowers*, G. Resch,* and M. Colantino? Dept. of Physiology. University of Missouri-K.C. The thyroid stimulating hormone (TSH) and prolactin (PRL) response to TRH, and luteinizing hormone (LH) response to LHRH was studied in male spontaneously hypertensive rats (SHR) and male normotensive Wistar Kyoto controls weighing 180 to 225 grams. The responses were examined 48 h after placement of Blood samples (400 ~1) indwelling carotid artery catheters. were withdrawn from the catheter at 0, 10, 15, 30, and 45 min for TSH and PRL determination after TRH (10 pg/kg) injection. Serum TSH, PRL and LH were measured by double antibody radioimnunoassays. The SHR had higher (p < 0.05) mean baseline TSH (1700 + 325 rig/ml) than the normotensive control rats (718 + 314-rig/ml) and displayed a greater TSH response to TRH at all sampling times through 45 min than the controls. The mean basal serum PRL was higher (p < 0.05) in the SHR (26.1 + 2.1 rig/ml) than the control rats (16.3 + 2.8 rig/ml). The mean APRL (difference between peak response and baseline levels) was greater (p < 0.01) for the SHR (12.0 + 0.8 rig/ml) Although the mean than for the controls (6.2 2 1.9 rig/ml). baseline serum LH for the two groups was similar, the ALH was less (p < 0.001) for the SHR (126 512.8 rig/ml) than for the The results of the study suggest that controls (252 + 24.8). The the hypothalamg-hypophyseal axis is altered in the SHR. changes in pituitary release of TSH, PRL and LH in the SHR is compatible with decreased central dopaminergic activity.

ALCOHOL AND NICOTINE ON CARDIAC PURKINJE FIBER REPOLARIZATION. W.H. Thies and K. Greenspan. Dept. Physiology, Indiana Univ. Sch. Med., Terre Haute Ctr. for Med. Ed., Terr? Haute, IN 47809 Our studies have demonstrated that nicotine (N) produces cardiac arrythmias by inducing changes in impulse formation and propagation. In addition, our earlier studies have shown that ethanol (E) and N can significantly effect the time Our course of canine cardiac purkinje fiber repolarization. present studies were undertaken to investigate the combined effects of N and E on the electrophysiologic properties of purkinje fibers. Standard intracellular electrocardiac physiologic techniques were utilized upon excised canine After equilibration, the tissues cardiac purkinje fibers. were superfused with Tyrode's solution containing N (0.5 mM) E (7 mM), or both. As previously reported, E increased the rate of repolarization (20%) primarily through an increase in the slope of phase 2. N alone also caused a statistically sigHownificant increase (27%) in the rate of repolarization. when the tissues were exposed to N prior to E superfusion ever, was the change in repolarization usually noted with E alone instead of an increased repolari zation rate reversed. Hence, there occurred a decrease in the rate of repolarization. Thus, in an apthe combined administration of the E and N resulted parent and unexpected antagonism. (Supported by Grant #H6 1647 from NHLI).

POTENTIATION & PRODUCTION OF HYPERTENSION IN SHR & WKY RATS BY ORAL CADMIUM FEEDING. Gurdarshan S. Thind. V.E. Lacaden* and Nancy C. Flowers. Hypertension Unit, Cardiology Div., University of Louisville School of Medicine, Louisville, Ky 40202. A colony of 14 SHR and 12 WKY rats was fed ad libitum a low cadmium (Cd) diet and de-ionized distilled drinking-r (DW) fortified with essential metals. Five ppm Cd was added to DW of 7 SHR and 6 WKY rats. Total body weights and indirect systolic blood pressures were done every 2 weeks. The total body weights were significantly lower (P < 0.05) in Cd-SHRs from 24 weeks onwards. There was non-persistent but significant (P < 0.025-0.05) further hypertension in Cd-SHRs at 4, 14, and 18 weeks, and hypertension in Cd-WKY at 14 weeks. Sustained hypertension was present in Cd-SHR and Cd-WKY rats from weeks 22 onwards with an average increase of 29 f 2 (SEM) and 26 + 4 m m Hg respectively after Cd-feeding compared to non-Cd fed SHR and WKY rats. The last blood pressures were taken at end of 32 weeks of Cd feeding. We conclude; (1) low-dose Cd feeding (equivalent of human Cd exposure) produced sustained hypertension in WKY rats and accentuated hypertension of SHRs, (2) average Cd-induced blood pressure elevation in SHR and WKY rats was significantly higher (P < 0.01-0.001) than in LongEvans rats (Physiologist 18:420, 1975), (3) apparently, Cd feeding resulted in blood pressure elevations sooner in SHR 81 WKY rats than in Long-Evans rats, and (4) inadvertant Cd exposure may potentiate genetic predisposition to hypertension in man.

EFFECTS OF ONE STAGE VS. TWO STAGE OCCLUSION ON INFARCT SIZE. J. X. Thomas, Jr., S. B. Jones and M. J. Barber*. Dept. of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153. Previous investigations have employed a two stage occlusion (TSO) model for producing myocardial ischemia. TSO involves an initial 15 min of 70-80% restriction followed by total ligation and has been shown to reduce the incidence of early arrhythmias and ventricular fibrillation. In using TSO, we have noted less severe changes in the following parameters in comparison to one stage occlusion (OSO): 1) cyanosis of affected muscle, 2) epicardial conduction delays and 3) decreases in contractile force. Therefore, we have chosen to evaluate the effect of OS0 vs TSO on infarct size (IS). Four dogs in each group were anesthetized with pentobarbital, and thoracotomized on the left side and the LAD artery was isolated just above the apical branch. In OS0 and after the 15 min constriction in TSO, the LAD was ligated for 6 hrs. Dogs were sacrificed, hearts excised, left ventricles cut free, sectionfor 10 min in nitro-tetrazolium blue stain ed, and incubated for dehydrogenases. Infarcted unstained tissue was dissected from normal, both were weighed, and expressed as % of left ventricular wt. IS for OS0 and TSO were 26.4421.12 and 12.342 .52 respectively (p PGE2)5-HT,AII>NE. With respect to the drug sensitivity, BK and AI1 were the most potent (ED and lastly by H?~";'",~~' followed by 5-HT(sl0 -8M) and NE(EDso~10 '6M).While the veils ap&&rPGE2 t PGAl ed to be more sensitive than the arteries, the differences were not significant (~7.05). It is concludthe rabbit umbilical vessels are ed that, at term, primarily sensitive to BK, Hist and PGF2,, with BK 1000X more potent than either Hist or PGF2,.

G (n=7); 4 ml/kg in

dehydrated S (n=9). Only MAP was significantly different (p< 0.001) between dehydrated G and S. Thus, IFP in the loose skin in conscious rats became negative only after slight dehydration. No significant differences in IFP or IFV were found between hypertensive and normotensive rats in either hydrated state. These results do not support the concept of decreased interstitial


30 o/o0 sea water. In the present study, phospholipids were extracted from gill microsomal membranes of F. heteroclitus 48 hours after transfer from 16 o/o0 sea water to fresh water ("0 o/00"), to a new tank of 16 o/00, or to 30 o/o0 sea water, and were separated by thin-layer chromatography into six fractions. Quantitative phosphorus analysis revealed that the only phospholipid class showing significant (~~0.01) salinity-related differences in percent composition was lysophosphatidyl choline (LPC). In four experiments, each using 6-9 fish from each salinity, LPC comprised 2.3?0.5% (mean+S.E.) of the total gill membrane phospholipids from fish acclimating to 0 o/00, while the values for 16 and 30 o/o0 were 5.320.6 and 5.5+0.3X respectively. Since lysophospholipids are known to possess detergent qualities, the decreased LPC in membranes of fish acclimating to fresh water may produce a tightening or masking effect on the Na++K+-ATPase, reducing the activity and/or number of functional sodium pumping sites. (Supported by American Heart Association, Virginia Affiliate.)

INTERSTITIAL FLUID PRESSURE AND VOLUME IN l-KIDNEY GOLDBLATT HYPERTENSIVE RATS. C. Trippodo. Research Division, --Nick Ochsner Medical Institutions, New Orleans, La. 70121. Microporous polyethylene capsules with attached catheters were implanted subcutaneously in the loose skin dorsal to the pectoral girdle in rats. Eleven of these rats underwent the lkidney Goldblatt procedure (G) and nine were sham operated (S). Four weeks after surgery measurements were made in the conscious animals. Mean arterial pressure (MAP), interstitial fluid pressure by the capsule technique (IFP), and interstitial fluid volume (IFV) were 178 f 7 mm Hg, + 0.3 + 0.6 mm Hg, and 240 f 6 ml/kg, respectively in G; and 117 f 3 m m Hg, + O.8* 0.4 mm Hg, and 255 ml/kg in S. Only MAP was significantly different (p< 0.001) between G and S. Similar experiments were performed on separate groups of G and S except that they were maintained on sodium-free diet and water restriction for one week prior to measurements. MAP, IFP, and IFV were 163* 8 mm Hg, -1.8 f 0.6 m m Hg, and 235 f 3 ml/kg, and 128 _+ 2 m m Hg, -3.3





STUDY ON ALTERATIONS IN SOLEUS MUSCLE FROM THE BURNED LIMB. J. Turinsky, R.E. Shangraw*, R.C. Henrikson*. Depts.Physiology and Anatomy, Albany Medical College, Albany, NY 12208. A 3-set burn on one hind limb in 90°C water is followed by biphasic alterations in glucose metabolism by skeletal muscle from the burned region but not from the contralateral unburned region of the rat. Glucose uptake and lactate release by soleus muscle from the burned limb are depressed at 4 hrs but increased above control at 3 days post-burn. To study factors responsible for these alterations, temperature, structure and water content of soleus muscles were evaluated in this type of injury. The subcutaneous temperature of the calf of the burned limb rose from pre-burn 35.620.4 (SE)OC to a maximum of 53.4+0.7'C at 9 set post-burn and temperature between the soleus and fibula rose from 36.4+0.4'C to 49.421.3'C at 15 set post-burn; both temperatures returned to normal by about 3 min post-burn. Electron microscopic examination of soleus muscles from burned limbs at 4 hrs and at 3 days post-burn showed no structural alterations of muscle cells. Wet weight/dry weight of soleus muscle from the burned limb was elevated 12% (plO mmBg decreased RENA andABP for the duration of the lung inflation. Bilateral cervical vagotomy (CV) decreased the duration of the response, but not the magnitude. Stellate ganglionectomy (SG) abolished decrease i n ABP, but the RENA decreases remained the in 2 of 3 animals. Distention of cardiac chambers via indwelRight ling bal loons resul .ted in decreases in ABP and RENA. and left atria1 stretch caused decreases in RENA during halloon inflation and deflation. ABP was decreased during the entire inflation. Ventricular stretch decreased BP and RENA for the duration of the inflation. CV abolished all RENA changes I but only attenuated the ABP responses . SG abol ished (CP) vagal afferents all ABP responses Cardiopulmonary wpear to play a dominant role in the control of RENA, while CP sympathetic afferents play a minor role. (Supported by Grant HL 16511 and the Medical Research Service of the VA).

UPTAKE OF NEUTRAL AMINO ACID 14C-CYCLOLEUCINE BY ISOLATED CEREBRAL MICROVESSKLS. Lester A. Wade* (Spon: J.C. Pisano). Dept. Physiology, Tulane Medical School, New Orleans, LA 70112. It has been suggested that the endothelium of cerebral microvessels may be the location of the blood-brain barrier, and the site responsible for regulating the movement of nutrients neutral amino acids) between plasma and brain. To bs* examine the transport systems found in isolated cerebral microvessels, we studied the uptake of neutral amino acid 14C-cycloleucine. Microvessels were isolated from rat cerebral cortex by means of the modified methods of Goldstein et al. (J. Neurochem. 25:715, 1975). Cerebral microvessels were incubated at 37°C in a solution of 14C-cycloleucine (10uM) for periods lasting l-5 minutes. The uptake of 14C-cycloleutine (1OuM) progressively increased as the period of incubation increased. There was a neglibile uptake of 14C-cycloleucine (1OuM) when microvessels were incubated at 4°C or boiled and incubated at 37'C. The uptake of 14C-cycloleucine (1OuM) was inhibited when a second neutral amino acid (3OuM) At a three minute was added to the incubation fluid. incubation, uptake was inhibited more than 45% by L-tyrosine, In agreement L-tryptophan, L-isoleucine and I.,-methionine. with --in vivo studies, these s-in vitro observations are consistent with the presence of a neutral amino acid transport (Supported by E.G. Schleider system in brain capillaries. Education Foundation).

OSCILLATORY BREATHING PATTERNS OF NEWBORN INFANTS. 2T.B Waggener*, I.D. Frantz III*, A.R. Stark*, R.E. Kronauer.* Div. Appl. Sci. Harvard Univ. Camb., MA 02138. Dept. of Ped. Harvard Med. Sch. Boston, MA 02115 (SPON: H.W. Taeusch, Jr.) Breath-to-breath values of tidal volume (VT), breath period (TT), and minute ventilation (Ve) were analyzed by digital band pass filters for 10 healthy full term infants, aged l-4 days. Infants were monitored in Quiet Sleep (QS) and Active Sleep (AS) with a pneumotach and face mask. Oscillatory patterns were seen in Tie, VT, and TT. Much of the increased var iability seen in AS is due to these osci llations occurring at several cycle times (CTs). Oscillations typical ly were not seen in QS, except transiently following a sigh. AS patterns included bursts of oscillations of 6-10 set CT and both bursts and sustained oscillations of 16-25 and 40-60 set CT. Five infants had significant oscillations with a 32 set CT as well. Sigh stimulated transients in QS show the same CTs seen in AS. Periodic breathing in infants is a regularly recurr ing pat tern of 5-10 set of apnea followed by lo-15 set of breathing, seen predominantly in AS and rarely seen i n in. I fants less than 5 days old. Our ve oscillations of 16-25 set CT occasionally became so strong as to include 2-3 set apneas at their minima . Presumably, stronger oscillat ions would produce apneas in the 5-10 set range and be recognized as 40-60 set CT if strong periodic breathing. Oscillations of enough, might cause 15-25 set apneas. (Supported by NIH grant No. 2ROl HL 16325-O 3).

A METHOD FOR RAPID AND CONTINLJOUS MEASUREMENTS OF GASES IN BLOOD BY MASS SPECTROMETER. P.D. Wagner, R.A. Gaines*and J.J. Struthers? Dept. of Medicine, UCSD, La Jolla CA 92093. Measurement of gas concentrations in blood by mass spectrometer (MS) has centered on a plastic membrane-coated sampling catheter through which gases diffuse directly into the vacuum system of the MS. In such systems, the signal is flow dependent, affected by the.boundary layer, difficult to calibrate and the response time (RT) is inherently long, of the order of likely to occur with a minute or more. A long RT is especially soluble gases dissolving and being retained in the catheter t onomet er (CCT) membrane. We have deve 1.oped a counter-current for measuring gases in blood by mass spectromet er. A thin vertical glass tube spinning on its long (vertical)axis is supplied from above by blood containing the gas to be measured and from below by nitrogen. Effluent gas at the tip of the tubeis sampled by the standard respiratory gas inlet of the MS. By appropriately choosing the geometry of the tube and the perfusing blood and gas flow rates, 90%RT of. stopped. D were monitored until t=5 hr, returned to their cages and observed for 48 hr. Four N treated and 1 Sa treated D survived (X2=4.41, p < 0.05). At t=2.25, 2.5, 3 and 4 hr, N treated D exhibited increased CI, VOz, and LVSWI associated with increased HR and MAP. At t=5 hr, PVR was decreased in D receiving N. In this model, N inhibits the deleterious effects of S and improves survival.

EXTRACTION, SEPARATION AND PARTIAL PURIFICATION OF PLASMA ANGIOTENSIN I AND II IN ONE AND TWO-KIDNEY HYPERTENSIVE AND NORMOTENSIVE RATS. E.K. Woody* and A.L. Baccus* (Spon Atlanta Univ., Atlanta, Ga. 30314 - - : J.B. Myers). Thirty male-Sprague-Dawley rats (190-250 gm) were divided into 3 groups, normotensive, l-kidney Goldblatt (l-kg) and 2-kidney Goldblatt (2-kg) animals. Each group consisted of 10 rats. After 7 and 14 days, respectively, weights and blood pressures were recorded. After the 14-day period all animals were sacrificed by decapitation and whole blood was collected and diluted in a cooled 10% solution of EDTA and isotonic saline. A second series of rats, normotensive, l-kg and 2-kg (10 per group) were weighed and blood pressures taken at 7 and 30 days. All animals were then sacrificed and whole blood collected as stated previously. Plasma was obtained by centrifugation of each sample of whole blood. All plasma samples of the respective groups were then pooled and placed on individual Dowex AG(SOW-X2) cation-exchange columns. The angiotensin peptides were extracted simultaneously and each sample was then lyophilized and stored. Sephadex (G-100) columns were used for separation and partial purification. Protein concentration was measured on each reconstituted sample (in Trisbuffer) and immunodiffusion assays were carried out (with standards) in order to separate and estimate the amount of AI and AI1 in each sample. Results indicate that AI and AII, based on the specific antibody reaction can be qualitatively identified. (Supported by Grant RR-8006 from the General Research Support Branch, Division of Research Resources, NIH).


THE EFFECT OF EXERCISE DURING HYPERBARIC EXPOSURE ON THE J.R. Wright*, K.J. Schniegenberg*, TIBIA OF THE MOUSE. J.D. Dunbar* and H.S. Weiss. Dept. of Physiology, College of Medicine, The Ohio State University, Columbus, Ohio 43210. The combined effect of exercise and pressure on dysbaric osteonecrosis was tested in four-week old female mice. Four groups were studied: (1) both pressure (5.24 ATA for for 6 wks) and exercise (alternate 2 hr/day, 5 days/wk, 15 min periods of swimming and resting during hyperbaria), (2) pressure only, (3) exercise only, and (4) untreated controls. Standard Navy decompression schedules were observed, Mice were sacrificed l-2 weeks after the end of the 6 week treatment period. Hind legs were disarticulated at the hip The plates of the tibias were and X-rayed (25 KeV/12 set). Medullary calcification was identified examined blindly. significantly more frequently in the exercise plus pressure Whole tibia density treatment than in the other groups. was determined according to Archimedes principle. Densities were 6% less than control values (p< .OOl> in the group Density was not subjected to both pressure and exercise. affected by exercise alone or pressure alone. The results indicate that exercise during hyperbaric exposure may be an important factor in dysbaric osteonecrosis.

EFFECT OF ACTIVITY OF LATERAL CILIA ON INFLUX OF AMINO ACIDS S. H. Wright and G. C. Stephens. Dept. Dev. and IN MYTILUS. Cell Biology,mity of California, Irvine, CA 92717. The Michaelis constant for influx of glycine into intact, active Mytilus is much lower than that obtained from studies employing preparations of gill tissue (2-5 PM vs. --in vitro 35-40 PM), yet gills are the primary site of uptake of amino This difference in K 's is due to acids in intact mussels. the presence of significant unstirred layers i k --in vitro gills resulting from the inactivation of lateral cilia which occurs Reactivation of lateral cilia by topical upon isolation. application of serotonin (5-HT) results in an increase in perfusion of the tissue and a concomitant increase in @flux Concentrations of 5-HT less than loM of 1 FM glycine. Between concentrations of 5-HT of havg no effegt on influx. and loM, influx of glycine increases from 0.1 ymoles/ 10(g-hr) to more than 0.5 pmoles/(g-hr). 5-HT has no effect on uptake of glycine into intact animals having spontaneous Treatment of isolated gills with activity of lateral cilia. 5-HT reduces the Kt for influx of glycine from control values are consistent with the of 40 PM to 20 PM. These observations hypothesis that in vitro preparations of gill tissue are associated with unstirred layers capable of introducing a significant bias into determinations of transport kinetics. Thus conclusions drawn concerning the physiology of intact animals from in vitro studies may be erroneous. (Supported by Grant OCE7F12183from the NSF)

SIZE, AGE AND GRAVITY AS DETERMINANTS OF STRENGTHS OF FEMURS AND OF BONE-TO-LIGAMENT JUNCTIONS. C.C. WUNDER, C.M. TIPTON, R.D. MATTHES*. and K.M. COOK*. Universitv of Iowa. Iowa City Iowa #52402. Iowa 52242 aid Goes Cedar Rapid;, Size corrections are necessary when altered body-growth We separated the medial accompanies experimental treatment. collateral ligaments from the tibias and we bent femurs from 76, one-G, male Sprague-pawley rats plus 26 grown for a week in 3-G centrifugation (Aviat. Space. Environ. Med. 48:339, 1977). Bending measurements were supplimented by a 24-rat, pilot, weightlessness-study (simulated by harness-suspension). For differences dependent on growth of the femur's length L (cm) with age t (days), strength S increases with size at norFor bones of a given age, mal gravity g (one G): S = A La. S exhibits the opposite L-dependence; S increases with g, sugS=B Lb x 10-c' t gesting S would grow slower without gravity: x (1 + Dg). Femur Junction Breaking Moment Matgrial Strength Separation Force S dyne-cm 10' dvne-cmmZ lo4 dyne

THE HEMODYNAMIC ACTION OF Mg++ DURING ISOPROTERENOL STRESS. 3.C. Yeager*, R.F. Morriso& and S.G. Iams* (SPON: D.L. Beckman). tast Carolina University, Greenville, N.C. 27834 Reports on isoproterenol (ISO) induced cardiac necrosis imply that severe systemic hypotension produces injury by reThe deleterious effects of inducing coronary blood flow. creased heart rate (HR) and increased activity of Cat+ pump Pretreatment with Mgtt has mechanisms have also been noted. demonstrated histologic and electrolytic myocardial protection. In this study 3 groups of unanesthetized, unrestrained, virgin male Sprague-Dawley rats (350-42Ogm), instrumented for monitoring blood pressure (BP) and ECG, were given subcutaneously a 1.0 ml solution of 155mg Mg-aspartate, 1.0 ml .9% NaCl or a needle prick (SHAM) respectively 30 min prior to a 25mg/ 1OOgm subcutaneous injection of L-13). Plasma Mgtt levels of 6.5 mEa/L at 30 min significantly lowered both BP and HR. NaCl or the SHAM injection had no effect. After ISO, BP in all 3 groups transiently decreased, but returned to control values within 15 min. During the following 6 hrs hypotension occurred only in the Mgtt group; mean BP fell by 120 min, but never dropped below an average of 86 mmHg (control = 112mnHg). All 3 groups showed significant increases in HR 1 min post ISO, lasting the 6 hours. HR in the Mgtt group was consistently lower than in the NaCl or SHAM groups. Without Mgtt, IS0 in the dose given did not produce prolonged systemic hypotension. With Mg++ some cardioprotection may be derived from reduced HR and possibly from reduced afterload. (Supported in part by the North Carolina Academy of Science).

A a B b C




x lo4

4.0 * 0.2 1.66 x 1010 -6 * 1 86 f 21 24 f 3%


3.3 0.2

92 -4.1'0.6 55



19 f 1%

* 0.2 1.65 3.5 * 0.3







REGIONAL Cl&L NuMnERS AND RESPIRATION IN FROG BRAIN. R. Yeaman * and R. L. Potter. Dept, Biology, California S%te University, Northridge, Cal. 91330. The percent increase in respiration in K+-enriched Ringer and the respiration in Na +-free Ringer of the (1)olfactory lobe-telencephalon (2)diencephalonmmesencephalon and (y)hindbrain of the bullfrog is proportional to the number of glia and neurons per mg wet weight, respectively. Oxygen electrodes measured the rate of oxygen consumption in normal amphibian Ringer, K+-rich, and Na+-free Ringer of tissue pieces minced finely. Homogenization of the brain regions in a flask with 5 mn glass beads on a shaker and periodic counts of nuclei in aliquots mixed with methylene blue examined under 500 power produced total, neuronal and glial cell counts. The hindbrain respires at l/4 of the rate of the other two brain regions in Na+-free Ringer. Raising the concentration of Na+ ions to 20 m enhanced the respirat&m of the hindbrain almost twice as much as for the more rostral regions. The two rostra1 regions of the brain contain about three times as many total cells and glia as the hindbraln. The two rostral regions also contain about 2-3 times as many neurons as the hindbrain. Neurons compose l/l 5 to l/g of the total cell population. The dorsal and ventral telencephalon, diencephalon, mesencephalon and cerebellum all accelerate respiration by more than m by incubation in 40 to 59 &I K+rich Ringer.

RES-INSULIN RELATIONS AND THE GLUCOSE DYSHOMEOSTASIS OF Department ENDOTOXIN SHOCK. M. R. Yelich ana J. P. Filkins. of Physiology, Loyola University of Chicago, Maywood, 11.60153 Previous studies have indicated that depression of the reticuloendothelial system (RES) plus minute doses of endotoxin (l-5 ug/300 gm rat) sensitized to insulin lethality and hypoglycemia (J. --of the RE Society 22: 461, 1977). The present study evaluated the influence OGRES depression using colloidal carbon blockade (32 mg/lOO gm iv, 4-6 hrs prior) in male Holtzman rats on insulin sensitivity, gluconeogenesis, glucose oxidation, and both hepatic portal and systemic *no-reactive insulin (IRI) levels. RES depression resulted in: sensitization to insulin convulsive seizure deaths; increased insulin hypoglycemic nadirs; depression of gluconeogenesis as evaluated in isolated hepatocytes as well as in vivo using 14C-alanine to "C-glucose conversion indicesFand enhanced glucose oxidation by both isolated epididymal fat from a 400 mg "C-glucose pads and whole body 14CO;! production load ip. Glucose stimulated IRI levels and particularly IRI/glucose ratios in both portal and systemic blood were significantly elevated by RES depression. The data suggest the following relation between RES function and insulin in the glucose dyshomeostasis of endotoxin shock: endotoxemia + RES of gluconeogenesis depression -t hyperinsulinemia -t depression and enhanced glucose use + hypoglycemia. (Supported by NIH Grant HL 08682.)

IN VITRO EFFECT OF TOLUENE DIISOCYANATE ON CYCLIC ADENOSINE I. Yevich and B. T. MONOPHOSPHATE IN RABBIT LYMPHOCYTES. Butcher*. Dept. of Medicine, Tulane University, New Orleans, La. 70112. Inhalation of toluene diisocyanate (TDI) vapor can produce asthma. Previous work in this laboratory demonstrated that The TDI stimulates CAMP in human peripheral lymphocytes. direct effect of TDI on tracheobronchial and peripheral lymphCells ocytes was studied using cells isolated from rabbits. were incubated with agonists for 10 minutes, centrifuged, and Dose respo;s;os:;ET;M) processed for CAMP radioimmunoassay. with TDI (1O-2 to 10F6M), and isoproterenol (10' TDI at 1 x 10e3i maximally stimulated periwere obtained. pheral lymphocyte CAMP 100% and tracheobronchial lymphocyte CAMP 300%. However, a maximal CAMP stimulation of 100% by isoproterenol was observed at 10m8 to lo-9M in peripheral lym hocytes, and a 200% CAMP stimulation in a range between in tracheobronchial lymphocytes. The results lo- 7 to lo-8M demons 'trate that rabbit and human peripheral lymphocytes reIn addition, the findings spond in a similar manner to TDI. lymphocytes sugges t that one possible using t racheobronchial asthma may be the altermode of action of TDI in producing in the cell membrane. Further studies ation 0 f adenyl cyclase should indicate whether TDI is acting at the beta recep tor site.

INHIBITORY MOTOR NERVES IN THE GUINEA-PIG TRACHEALIS MUSCLE P.Yip* and R.F. Coburn Dept. of Physiol., Univ. of Pennsylvania,School of Medicine, Philadelphia, Pa, 19104. We compared effects of field stimulation (FS) of intramural nerves in the in vivo cervical trachealis muscle (TM) on n4 tension, with effects of electrical stimulation of the sympaAll stimulations were perthetic trunks (SS) or the vagus. voltage. formed with 0.3 to 0.5 msec pulses at supe rmaximal iso-volume pressure TM tension was estimated with intraluminal measurements with the cervical trachea closed at both ends with The animals were ventila ted stoppers and filled with saline. via the thoracic trachea. In atropinized animals, bilateral stimulation of the cut vagi had no effect on TM tension. FS produced relaxations equal to maximal isoproterenol relaxations. Maximal relaxations at 20 Hz with SS averaged 62 f 21 (SD) % of FS relaxations. FS and SS relaxations, during atropine, were usually seen with single pulses delivered every 2 seconds. Frequency-response relationships were not significantly different with SS and FS: 40% of max. relaxation - SS 2.3 Hz, FS 1.8 Hz. 70% of max. relaxation - SS 4.6 Hz, FS 3.9 Hz, 6-hydroxydopamine, 100 mg/kg, essentially abolished both SS and FS relaxations; at lower doses this drug has similar ef fects on SS . and FS data. We conclude . (a ) There are no inhib itory motor nerves running in the vagus.(b) Since FS should stimulate the total population of inhibitory nerves, the similar characteristics during FS and SS suggest most of the inhibitory motor nerves run in sympathetic trunks. HL 19737

EFFECTS OF FLUORIDE OrI THE HYDRO-OSMOTIC RESPOlJSE OF THE TOAD BLADDER T O VASOPRESSI:J (ADH). T . Yorio* and R. Sinclair. Depts. of Pharmacology and Physiology, North Texas State University Health Science Center/TCOfl, Ft. Worth, TX. 76107. A consequence of methoxyflurane anesthesia is an associated nephrotoxicity. Fluoride, a metabolite of methoxyflurane, has been implicated as the causative agent in polyuric post-methoxyflurane renal failure. The present study examines the effects of fluoride on the hvdro-osmotic actions of ADH in the --in vitro preparation of the"toad urinary bladder. Fluoride on the serosal side of the bladder oroduces a dose dependent inhibition of the hydro-osmotic effbct of vasopressin. At lo-* 11 and 5 X 13-3 M NaF the hydro-osmotic response to ADH is inhibited by 50 and 25% respectively. In the presence of an osmotic gradient and in the absence of ADH, NaF (13 mM) had no effect on basal I-120 flow. The hydro-osmotic response of cyclic-AMP was also inhibited by fluoride, suggesting an action subsequent to the endogenous formation of this nucleotide. Besides fluoride's well known inhibitory effect on glycolysis it may also have a direct effect It has been reported that patients on the ADH effector site. with renal dysfunction following methoxyflurane anesthesia have urinary levels of fluoride that may exceed 1 mid. Thus, although relatively high concentrations of fluoride were needed to elicit this response, it may be a contributing factor in the development of polyuric renal failure. (Supported by TCOrl Faculty Research Grant 34360.)

CEREBRAL ACTIVITY PRECEDING SPEECH PRODUCTION. D. H. York and T. W. Jensen*. Dept. of Physiology and Communications Dlsorders Unit, University of Missouri, Columbia, Missouri 65212 Whether there is a cortical motor program of cerebral activity which can be demonstrated preceding a voluntary motor act has been speculated about for a considerable period of time. The present study was undertaken to examine the cerebral activity preceding the utterance of specific sounds or words. Signal averaged EEG signals recorded differentially between the midline intra-aural position (Cz) and left mastoid were evaluated for several periods of time preceding an utterance. Subjects (n = 26) were right-handed adult females with a mean age of 23.6 years. Several different utterances were evaluated in each subject including the vowel /a/, syllables such as /ut/ and the words 'yes,' 'no' and 'ate.' Each utterance voiced every 5 seconds was averaged 100 times with two breaks interposed during an experimental run, in order to reduce subject fatigue. Recordings of laryngeal EMG were also taken preceding any EMG activity associated with the production. The results demonstrated utterance specific cerebral activity,preceding speech across subjects. Also, if the subject thought of a particular utterance using the same experimental protocol as voicing, a waveform was produced that was similar to the voiced record. These results suggest that it may be possible to extract cerebral motor programming which precedes speech.

SERUM ALKALI-LABILE PROTEIN PHOSPHORUS INDUCTION IN RESPONSE TO OP\ALLY ADMINISTERED ESTROGEN IN A MARINE TELEOST WHICH LAYS PELAGIC EGGS. S.F. Yosha* and P.T. Cardeilhac. Coll. of Vet. Med. and Whitney Marine Lab., U of FL, Gainesville, FL 32610. Injection of estradiol-176 (E ) at a dose of 5 pg./g fish increased liver weight and elevate ii serum alkali-labile protein phosphorus (SALPP) levels in the pinfish (Lagodon rhomboides) from a level of