Noninvasive Estimation of Regional Myocardial Oxygen Consumption by Positron Emission Tomography with Carbon-11 Acetate in Patients with Myocardial Infarction Mary Norine Walsh, Edward M. Geltman, Michael A. Brown, C. Gregory Henes, Carla J. Weinheimer, Burton E. Sobel, and Steven R. Bergmann Cardiovascular Division, Department oflnternal Medicine, Washington University School of Medicine, St. Louis, Missouri
We previouslydemonstratedin experimentalstudiesthat myocardialoxygenconsumption (MVO2)can be estimated noninvasively with positron emission tomography (PET) from
analysisof the myocardialturnoverrate constant(k)after administrationof carbon-I1 (11C) acetate.To determineregionalk in healthyhumansubjectsandto estimatealterationsin MVO2accompanyingmyocardialischemia,we administered[11C]acetate to five healthy humanvolunteersand to six patientswith myocardialinfarction.Extractionof [11Cjacetateby
the myocardiumwas avidand clearancefrom the blood-poolrapidyieldingmyocardialimages of excellentquality.Regionalk was homogeneousin myocardiumof healthyvolunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was
not differentfrom valuesin myocardiumof healthyhumanvolunteers(0.061±0.025 compared with 0.057 ±0.008 min1). In contrast, MVO2 in the center of the infarct region
was only6% of that in remoteregions(p < 0.01).In four patientsstudiedwithin48 hr of infarction and again more than seven days after the acute event, regional k and MVO2did not
change.Theapproachdevelopedshouldfacilitateevaluationof the efficacyof interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional
MVO2andmetabolicreserveundetlyingcardiacdiseaseof diverseetiologies. J Nucl Med 30:1798—1808, 1989
oninvasive quantification of regional myocardial oxygen consumption has been an elusive and long standing objective ofcardiovascular research. Its utility
grafting. In addition, elucidation ofthe pathophysiology of syndromes such as angina with angiographically
is analogous to that of delineation of ventricular func tion, now readily accomplished by ventriculography or
normal coronary arteries (syndrome X) or of cardio myopathies ofdiverse etiologies requires quantification
echocardiography among other methods; or of assess ment of myocardial blood flow. Its potential value is underscored by clinical issues such as optimization of treatment of patients with ischemic heart disease re quiring titration of myocardial oxygen requirements and ventricularperformance, and by the importance of
of regional myocardial oxygen consumption and call mation of oxidative metabolic reserve. Despite the quantitative power of positron emission tomography and its sensitivity for detection of labeled,
delineating viable myocardium
after interventions
such
as coronary thrombolysis, essential for identification of patients who may benefit from subsequent additional Received Feb. 20, 1989; revision accepted
June 12, 1989.
For reprints contact: Mary Norine Walsh, MD, Cardiovascular Division, Washington University School of Medicine, Box 8086, 660 S. Euclid Ave., St. Louis, MO 63110.
1798
Walsh, Geltman, Brownetal
measures such as angioplasty or coronary artery bypass
physiologic substrates,
quantification
of carbohydrate
or fatty acid metabolism alone does not provide a direct measure of regional myocardial (1,2).
We have shown
oxygen consumption
that admixture
of diverse
sub
strates obscures changes in myocardial oxygen con sumption estimated on the basis of metabolism of individual substrates such as glucose or fatty acid (2). In addition, the myocardial handling of either labeled palmitate or glucose (or the glucose analogue, fluoro deoxyglucose) is critically dependent upon the level of
The Journal of Nudear Medicine
arterial substrate content as well as on the hormonal milieu (3—6). We recently hypothesized that measurement of oxi dation of acetate would provide an indirect measure of myocardial oxygen consumption (7-9). In contradis tinction to the case with glucose or fatty acid, metabo lism of acetate is confined virtually exclusively to mi tochondrial oxidation. We have demonstrated in iso lated perfused hearts (7) and canine hearts in vivo (8) that the extraction of carbon-i 1- (‘ ‘C) labeled acetate by myocardium is avid and that the clearance from the tissue is very closely correlated with both oxidation of labeled acetate to ‘ ‘CO2 and with myocardial oxygen consumption over a wide range of cardiac workloads. Furthermore, we have demonstrated that the quantita tive relationshipbetween myocardial oxygen consump tion and turnover of [“Clacetate is persistent despite marked changes in the proportion of substrate pre sented to the heart in vivo (9). The presentstudy was undertakento characterizethe turnover rate constant of [‘ ‘C]acetate by positron emis
emissiondata to verify proper positioningof the patient so that four to six of the seven cross-sectionaltransaxialimaging
planestransectedthe heart.Correctpositioningwas main tamed throughout the study with the use of a light beam and indelible marks on the subject's torso. Polyurethane molds were made individually for each subject prior to each study
and used to stabilizethe head, neck, and upper torso to minimize movement and maintain identical positions for
multipletomograms.Emissiondata werecollectedin the high resolutionmode with a reconstructedresolution(fullwidth at halfmaximum) of 13.5mm. To characterizemyocardialperfusion,we usedthe diffusi ble traceroxygen-15- (‘SO, t½ = 2.1 mm) labeled water and a method previously developed in our laboratory and validated in animals and patients (11—14).After collection of attenua
tiondata,0.4 mCi/kgof H2'5Owereinjectedas a bolusvia a large bore catheter inserted into an antecubital vein. Data werecollected beginningat the time ofadministration of tracer and continued for 150 sec in list mode with time-of-flight correction. After a 5-mm interval for decay ofactivity of tracer
to baselinelevels,40 to 50 mCi of oxygen-15-labeledcarbon monoxide (C'5O)were administeredby inhalation to label the blood pool. After a subsequent interval of 30 to 60 sec for
sion tomography in normal human subjects and in
clearanceof C'@Ofrom the lungs, data were collected for 5
patients with acute myocardial infarction and to use the ‘ ‘C myocardial turnover rate constant to estimate regional myocardial oxygen consumption.
mm. After an additional 5-mm interval for decay of radioac tivity to baseline levels, 0.4 mCi/kg of[' ‘C]acetate (t@= 20.3
mm) were injected as a bolus. In general, ‘ ‘C data were collectedfor 30 mm. In some controls, collectionswere con tinued for as long as 60 mm afteradministration of tracer.
METhODS
Analysisof TomographicData
Subjects
sion after administration of ‘ @O water, radioactivity emanating
Perfusion. To display the distribution of nutritional perfu
The protocol used was approved by the Washington Uni
versityInstitutionalReviewBoard(Human StudiesCommit tee). After the nature ofthe study had been explained to each subject, written informed consent was obtained. Five male volunteers with mean age of 28 yr (range 25 to 36 yr) comprised the control group. All had normal electro
cardiograms, no history of cardiac disease, and no known cardiac risk factors. Six patients (five male and one female) with transmuralmyocardialinfarction(documented by analy sis of plasma creatine kinase activity and by Q waves on the
fromthebloodpoolwascorrectedwiththe useofC'5Oanda methodvalidatedpreviouslyin our laboratory(11—14). In each pixel of the tomographic reconstructionobtained after administration of H2'5O,radioactivityemanating from the blood pool was subtracted to provide an image of blood flow
in the myocardium. Data reconstructedinto cumulative 120sec images were used to identify regions of diminished perfu sion in heartsof patients with myocardial infarction. Metabolism. To characterize qualitatively the distribution of radiolabeled acetate in the heart and obtain a myocardial
image, data were reconstructed into a single static 5-mm composite scan. The reconstruction encompasseddata col jected to acute interventions such as coronary thrombolysis or balloon angioplasty.Their mean age was 48 yr (range = 38 lected from 3 to 8 mm after administration of tracer, an to 61 yr).One patienthadsustainedinferiorinfarction,and intervalwhen blood-poolradioactivityhad declined substan fivehad sustainedanterior infarctions.Four (one withinferior tially. Images were used subsequently for placement of regions andthreewithanteriorinfarction)studiedinitiallywithin48 of interestbut not for quantitativeanalysis. For quantitative analysis, a single midventricular tomo hr ofinfarction were studied again at least 7 days after infarc electrocardiogram)werestudied as well.None had been sub
tion to define sequential changes in [‘ ‘Cjacetatemetabolism in normal and infarct zones.
graphic slice was selected from the reconstructed tomograms in normal control subjects. In patients, the reconstruction
containing the infarct region, as delineated from the H2150 perfusionscan, was used for analysis.In the case of anterior infarction,midventriculartomogramswere used. In the case bodypositronemissiontomographthat providessimultaneous of inferior infarction a more apical tomographic plane was acquisitionofdata sufficientfor reconstructionofseven trans used. Protocol Each subject was positioned in Super PElT I, a whole
axial slices with a center-to-centerslice separationof 1.5 cm,
anda slicethicknessof 1.14cm (10). A transmissionscanof the chest was obtained with a ring of germanium-68/gallium 68 to correct for photon attenuation ofthe emitted radiation. The transmission scan was viewed prior to the collection of
Volume30 • Number11 • November1989
Regions of interest with a volume of
1 cm3 were placed
circumferentiallyon each tomographic reconstruction. For midventriculartomograms,nine regionsof interest were em ployed. For more apical tomograms, three posterior regions were identified as well. An additional region of interest was
1799
assigned to the center of the left atrium or the left ventricular
cavityfordeterminationofactivity oftracer in the bloodpool. Regionsof interest in tomograms obtained after adminis tration of [‘ ‘C]acetate to patients were subdivided to encom pass regions of interest in normal, infarcted, and pen-infarct
0 S
E
Itissue.Normal regionswereidentifiedas those fullycontained z 0.
within regions of myocardium with normal perfusion (> 50% (I) of maximum flow) judging from the H2'5Otomograms. “In0z
farct― zoneswere identifiedas regionsof hypoperfusionwith
< 50% of maximum perfusion. In addition, the 1 cm3 region
@
S
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L@J0.;
of interest in the center of this zone of hypoperfusionwas identified as being the most ischemic zone and designated “central infarct―. Pen-infarct regions on either side of the U) > 0. infarct zone were delineatedas the regionsof interest imme
n ‘ 33 r
0.88
ys
0.036X
+ 0.021
diately adjacent to the infarct but within a zone of perfusion a: Iwith counts exceeding 50% of maximum activity of H2'5O.
The [‘ ‘C]acetate myocardialturnover rate constant (k),was obtained from the equation: q = e@t
0
I
2
3
4
5
6
7
8
9
0
MYOCARDIAL OXYGEN CONSUMPTION (pmol/g 1mm)
FIGURE 1 Correlation between the myocardial turnover rate constant
where, q = counts/voxel/minute corrected for physical decay, k = myocardial turnover rate constant, and
t = time It was calculatedfrom sequential90-120-secframes@ A mul tiexponential, least squares, curve fitting procedure was used
to fit myocardialtime-activitycurvesbeginningat the time of occurrence of maximal myocardial ‘ ‘C activity. Data were expressed also as the myocardial clearance half-time (t@1, =
measurednoninvasivelywith PETafter i.v. administration of [11C]acetateand MVO2measuredby direct arterial coronary venous sampling Obtained from 33 individual measurements in 18 anesthetized, intact dogs studied at rest or after myocardial work had been altered wfth sym pathetic stimulation or blockade, or after the pattern of
myocardialsubstrateuse had been changedby altering arterial substrate content after infusion of either glucose or lipid. The data presented here Is a summary of the results from previously published studies from our labors
ln2/k). tory (8,9).Thisrelationshipwas usedto estimateregional Myocardial oxygen consumption (MVO2)was estimated MVO2in humansfrom the myocardialturnoverrate con for each defined region of interest based on the relationship slant. between the myocardial turnover rate constant, k, and directly
measuredMVO2in 33 individualstudies in intact dogs (Fig. 1) (8,9). Although this relationship has not been established RESULTS directlyin humans, becauseof ethical considerations,we did not feelthatcoronarysinuscatheterizationwasjustifiablein Hemodynamics normal subjects. Coronary sinus catheterization in patients No adverse effects of administration of any tracer anddeterminationofarterial-venous differencescouldprovide were observed. All subjects tolerated the tomographic estimates of myocardial oxygen consumption, but would pro vide global, ratherthan regional, values. Because clearance of radioactivity from the arterial blood
procedures well. The rate-pressure product (heart rate x systolic blood pressure), an index of global myocar dial work, was calculated for all subjects. The rate wasso rapid(seeResults)spilloverfrombloodto myocardium
did not requirecorrection.We havepreviouslydemonstrated pressure product was lower in control subjects undergo ing tomography than it was in patients with infarction in experimental animals that spillover correction of data ob tamed after administration of [‘ ‘Cjacetate is unnecessarybe (7051 ± 1131 bpm x mmHg compared with9517 ± causeofthe rapid clearancefrom arterial blood (8). 3023, p < 0.05), presumably because of differences in autonomic nervous system activity. The rate-pressure Preparation of Tracers product was also lower at the time of follow-up 1 wk Oxygen-15 water, C'5O and [‘ ‘Clacetate were prepared as after infarction in the four patients studied than it was previouslydescribedin detail (7,15,16).PUrityof[' ‘C]acetate in studies within 48 hr of onset of infarction (7082 ± was typically greater than 99.5%. Preparations of 200—300 mCi,witha specificactivityofgreaterthan 1Ci/mmol,were 2654 at follow-up compared with 9879 ±3332 acutely, p < 0.05). achievedroutinely. Statistics Dataarereportedas means±standarddeviations.Signifi cance ofdifferences between groups were assessed with analy sis of varianceand post-hoc unpairedanalysis. Within groups
differenceswerecomparedwith the use ofpaired tests.Differ ences with a p < 0.05 were considered to be significant.
1800
Walsh, Geitman, Brown etaI
Assessment of Myocardial Perfusion Nutritional perfusion, assessed with H2'50, was ho
mogeneous in all subjects in the control group (Fig. 2). In contrast, all patients with myocardial infarction dis played diminished perfusion in a tomographic region that correspondedto the locus ofthe region of infarction
TheJournalof NuclearMedicine
•285
!14251756
1878
8 FIGURE 2 Mid-ventricular, transaxial, tomographic reconstructions from a representative control subject (P360). On the left is the reconstruction obtained after administration of 150 water, corrected for vascular radioactivity. On the right is the corresponding tomogram obtained after administration of [11C]acetate.In these mid-ventricular, transaxial reconstruc
tions,the septumis on the left, the lateralfreewallon the right,the anteriormyocardiumtowardthe top, andthe mitral valveplane,devoldof significanttraceruptake,towardthe bottom.Concordanceof distributionof tracerinthe perfusion and metabolicimagesis evident.The slight discontinuityof tracer uptakeseen in the septumin the H2150imageis related to statistical noise induced by correcting the image for radioactivity emanating from the blood pool. Uptake of [11C]acetatewas avid and resulted in myocardial images of high quality in all subjects.
delineated electrocardiographically (Fig. 3). The region of diminished perfusion defined with H215O was used
to distinguish infarct, normal, and pen-infarction re gions. Analysis of Data after Administration of t―CjAcetate An example of a midventriculartomographic recon struction obtained after intravenous administration of [“Clacetateon a normal subject is shown in Figure 2.
The homogeneity of myocardial ‘ ‘C activity observed and the quality ofthe image are representativeof results in each control.
A reconstruction from a patient with anterior myo cardial infarction is displayed in Figure 3. Both the H215O and the F'‘C]acetatetomograms
show markedly
decreased tracer in the anterior myocardium and rela tively normal distribution ofperfusion and metabolism in the septal and lateral walls. Quantitative
Analysis
As shown directly in studies in experimental animals (8,9), and confirmed in the human subjects studied here, [‘ ‘Cjacetate radioactivityin the blood pool dimin
ished by 90% to 95% from peak radioactivity, usually within 2 mm (Fig. 4). For each of the 9—12regions of interest placed on tomographicreconstructions,a multi-exponential curve fit was used to characterizedecay-correctedmyocardial time-activity curves from the time of occurrence of maximal myocardial ‘ ‘C radioactivity. In contrast to the biexponential clearance of ‘ ‘Cradioactivity ob served in isolated rabbit hearts (7) and in hearts of dogs in vivo (8,9), clearance of ‘ ‘C was monoexponential in both controls and patients (Fig. 5). This observation
is
consistent with the lower workload seen at rest in nonanesthetized, noninstrumented human subjects compared with that in anesthetized dogs and with pre liminary observations in humans reportedby Pike et al (17) and by Henes et al. (18). No second exponential
component could be identified even in two subjects studied for as long as 1 hr afteradministration of tracer. Clearance ‘ ‘C radioactivity from the myocardium was homogeneous
in control subjects (Table 1, Fig. 5).
The variation ofthe turnover rate constant within each tomogram, reflectedby the coefficient of variation, was
FIGURE 3 Mid-ventriculartomographic recon
structionsof perfusion(left)andoxi
dativemetabolism(right)in a patient @
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with acute, anterior, myocardial in farction (P354). A large anterior flow
deficitis evidentin the perfusionto mogram and a concordant decrease in myocardial oxygen consumption reflected by decreased [11C]acetate uptake is evident in the tomogram obtained after administration of [11C]
acetate.
@
Volume30 Number11 November1989
1801
from k (Fig. 1), in normal human subjects, calculated MVO2averaged0.97 ±0.23 @imol/g/min(Table 1). In contrast to the homogeneous clearance observed in hearts of control subjects, clearance of radioactivity from the myocardium of patients with infarction was
N
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Infarct
FIGURE 6 (A)Histogramdepictingthe regionalmyocardialturnoverrateconstantfromall regionsin normalsubjectsandin infarct, central infarct, pen-infarct, and remote regions in patients with myocardial infarction. (B) Estimates of regional myocardial
oxygenconsumptionin all regionsfrom normalvolunteersand from infarct, central infarct, pen-infarct,and remote regions in patients with myocardial infarction. There was no statistically significant difference between regions remote from infarction in patients and regions from normal human volunteers. Regional myocardial oxygen consumption
diminishedin pen-infarctregionsin patients,andwas severelydepressedin the zoneof infarction(p < 0.05 compared with remoteregions).
facilitates quantitative analysis of myocardial turnover rate without the necessity for correctingfor myocardial spillover from blood into myocardium (8,18). In normal subjects, uptake and clearance of ‘ ‘C was homogeneous and monoexponential. Use of the rela tionship between k and MVO2 established previously
cells constituting a heterogeneous population manifest ing phenomena integrated in the tomograms within selected regions ofinterest because ofthe limited spatial resolution of PET. This latter interpretation is sup
in canine hearts in vivo and the data obtained in the
least 7 days after the acute event, at a time by which
present study in human subjects yielded a calculated human myocardial oxygen consumption value of 0.97 @mol/g/min,somewhat lower but close to that prey
imaging with H2'5O, was markedly depressed and clear
function and metabolism in myocardium not destined to undergo infarction have recovered, did not change. Studies in experimental animals have demonstrated that with reperfusion, oxidative metabolism assessed with [‘ ‘C]acetate recovers within 1 wk in zones destined to recover and is predictive of recovery of ventricular function (23). Studies by others have shown that res toration of ventricular function is predicated on recov
ance was prolonged. Both are a result of diminished perfusion to the region. The diminished clearance di rectly reflects the reduction of myocardial oxidative metabolism. Overall oxygen consumption within zones of hypoperfusion delineated by H2'5Oin humans was —30%of that in normal zones, a finding consistent with the recognized magnitude of myocardial collateral perfusion in zones ofinfarction (22). Estimated oxygen consumption in the center of the hypoperfused zone
though enhanced glycolytic flux is seen in reperfused myocardium (2) and can be demonstrated with fluo rine-l8 (‘8f@) fluorodeoxyglucose (25), the prolonged imaging intervals requiredwith deoxyglucose as well as the dependency of myocardial uptake of this tracer on plasma substrate and hormonal concentrations pre cludes its use to quantify regional myocardial oxidative metabolism.
ously obtained by direct analysis with invasive proce
dures (19—21). In patients with infarction, uptake of [‘ ‘C]acetate in the center of the infarct zone, delineated by perfusion
ported by the finding that MVO2 in peri-infarct regions
in patients with infarction studied acutely and again at
ery of myocardial
oxidative
metabolism
(24,25).
Al
was @—6% of normal. Regions remote from the center
of the infarction exhibited normal myocardial uptake and turnover of tracerindicative of normal myocardial oxidative metabolism. Pen-infarction zones manifested prolongation of clearance indicative of diminished ox idative metabolism. These regionsmay be metabolically “stunned―. Thus, the diminution ofblood flow to myo cardium within these regions, although not sufficient to induce infarction, is sufficient to diminish regional work and regional MVO2.Alternatively,pen-infarction zones may contain a mixture of viable and infarcted
@
Volume30 Number11 November1989
Technical Considerations Results of this study indicate that the turnover rate constant after i.v. administration of [‘ ‘Cjacetate can be quantified by PET. We developed [“Cjacetate as a tracer suitable for assessment of regional myocardial oxygen consumption because it is metabolized virtually exclusively via mitochondrial oxidation (7—9).Oxida
lion ofacetate to CO2in mitochondria is coupled tightly to oxidative phosphorylation. We have shown prey ously that the turnover rate in isolated perfused hearts
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_______________________
Remote
Pen-Infarct
_______________________
Infc@ct
A FIGURE 7
Central
Infarct
0
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Infarct
B
Central
Infarct
Histogram displaying the myocardial turnover rate constant, k (A), and estimated myocardial oxygen consumption (B) from four patients studied acutely and again at least 7 days after the acute event. There was no change in regional k or MVO2with time in any region.
parallels regional myocardial oxygen consumption over a wide range of physiologic and pathophysiologic con ditions including ischemia and reperfusion (7). Com parisons of the myocardial turnover after intravenous administration
of [“Cjacetate with direct
measure
ments of myocardial oxygen consumption have dem onstrated the relationship between the myocardial turn
over rate constant (k) detected externally with PET, and MVO2 over a wide range (Fig. 1) (8,9). This rela tionship is not altered by changes in myocardial work or by the pattern of substrate utilization (9). Despite the fact that acetate is avidly extracted by the myocar dium with an extraction fraction of 30—50%, its oxida tion does not account for a large fraction of myocardial energy supply because it circulates in such low concen
trations in normal human subjects(80—100 Mmol)(26). Nonetheless,
the relationship
between the myocardial
turnover rate constant and MVO2 has not been estab lished directly in human beings. Values of MVO2 in humans estimated by extrapolation of the relationship obtained directly in dogs yield values that are somewhat lower than those that have been measured in human subjects (19—21).We recently reported that the rela tionship between k and the rate-pressureproduct (an index of myocardial work and therefore of myocardial oxygen consumption) obtained in healthy human vol unteers was indistinguishable from the relationship ob tamed in experimental animals (18). Nonetheless, the
In addition, we have demonstrated the utility of this technique in patients with coronary artery disease (14). Although tomography with H2150 permitted independ
ent delineation of normal from ischemic myocardium, correction ofmyocardial H2'5O for vascular radioactiv ity (which requires an independent measure of the blood pool with C'50) results in images of relatively
low signal-to-noise ratios. Although we recently vail dated a mathematical
approach to quantitate
myocar
dial perfusion in absolute terms (i.e., ml/g/min) using H2'5Oand PET which does not requirean independent measurement
of the blood pool, we chose not to use
the quantitative approach in the current study because it is less sensitive to estimates of flow in infarcted myocardium (27). Clinical Implications The resultsofthe present study indicate that positron emission tomography with [‘ ‘C]acetate,a tracer of myo cardial oxidative metabolism, provides myocardial im
investigatorsusing invasive techniques may reflect a
ages of high quality and permits estimation of regional myocardial oxygen consumption with results consistent with those obtained previously by invasive measure ments. Oxidative metabolism in the center of zones of infarction is markedly depressed and, in the absence of acute interventions, does not change with time. Acute
true interspecies difference in the relationship
interventions
discrepancy in values of MVO2 obtained nomnvasively
in the present study with values obtained by other between
k and MVO2. Although the rate-pressureproduct can be used to estimate MVO2in normal subjects,it reflects global, rather than regional, MVO2. In contrast, the PET approach developed permits sequential assess ments of regional MVO2. In the present study, areas of normal and hypoper
@
fusion were estimated using H2'5O and a technique developed previously in our laboratory to correct data for intravascularradioactivity.Regional perfusion using this approach correlates very closely with regional blood flow estimated with radiolabeledmicrospheres(11-13).
Volume 30 SNumber 11 November1989
are likely to restore oxidative metabolism
in jeopardized myocardium and can therefore be eval uated with the approach developed here. Accordingly, quantification of myocardial oxygen consumption with [‘ ‘C]acetateand positron tomography offers promise for objective, noninvasive characterization of the rela tive benefits ofdiverse interventions designed to salvage
1807
jeopardized, ischemic myocardium. In addition, the approach developed should be useful for evaluating regional MVO2 and metabolic oxidative reserve in the hearts of patients with cardiac disease of diverse etiol ogles and their response to therapy.
H2'5O.Circulation 1984; 70:724—733. 12. Knabb RM, Fox KAA, Sobel BE, Bergmann SR. Characterization ofthe functional significance of sub critical coronary stenoses with H215O and positron
emission tomography. Circulation 1985; 71:1271— 1278. 13. Knabb RM, Rosamond
ACKNOWLEDGMENTS The authors thank Theron Bairdand ColleenSchaab,RN for technical assistance, David Marshall, BS, James Bakke,
MS, and the staff of the Washington University Medical Cyclotron for preparationof tracers;and Becky Leonard for
preparationof the typescript.
TL, Fox KAA, Sobel BE,
Bergmann SR. Enhancement of salvage of reperfused ischemic myocardium by diltiazem. JAm Coil Cardiol 1986;8:861—87 1. 14. Walsh MN, Bergmann SR, Steele RL, et al. Deinea tion of impaired regional myocardial perfusion by positron emission tomography with H2'50. Circula tion1988;78:612—620. 15. Welch MJ, Ter-Pogossian MM. Preparation of short
and Blood Institute, Grant HL17646, SpecializedCenter of Researchin IschemicHeart Disease.
half-lived radioactive gases for medical studies. Rad Res 1968; 36:580—587. 16. Welch MJ, Kilbourn MR. A remote system for the routine production of oxygen-iS radiopharmaceuti cals. J Label Comp Radiopharmaceuticals 1985; 22:
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TheJournalof NudearMedicine
