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Effect of Strenuous Arm Crank Exercise on Platelet Function in Patients With Spinal Cord Injury Jong-Shyan Wang, PhD, Chih Fang Yang, MD, May-Kuen Wong, MD ABSTRACT. Wang J-S, Yang CF, Wong M-K. Effect of strenuous arm crank exercise on platelet function in patients with spinal cord injury. Arch Phys Med Rehabil 2002;83: 210-6. Objective: To investigate the effects of arm crank exercise on various platelet functions and prostacyclin in individuals with spinal cord injury (SCI). Design: Case-control study. Setting: Research project at a hospital-based exercise physiology laboratory. Participants: Seven men (with lesions at levels T11, n ⫽ 1; T12, n ⫽ 2; L1, n ⫽ 2; L2, n ⫽ 2) and 3 women (T12, n ⫽ 1; L1, n ⫽ 2) in the SCI group had SCI for at least 6 weeks. Ten age- and gender-matched healthy people who had not engaged in any regular physical activity for at least 1 year were selected as the control group. Intervention: All subjects exercised strenuously by using an arm crank engometer. Main Outcome Measure: Platelet adhesiveness on fibrinogen-coated surface and epinephrine-induced aggregation in vitro, plasma soluble P-selectin (sP-selectin), and urinary 6keto-prostaglandin F1␣ (6-keto PGF1␣) levels. Results: The SCI group had higher platelet adhesiveness and aggregability and plasma sP-selectin level, but lower urinary 6-keto PGF1␣ level than the control group. Platelet adhesiveness and aggregability were enhanced by strenuous arm exercise in all subjects, but only in the SCI group was sP-selectin level increased by exercise. Strenuous exercise raised the levels of 6-keto PGF1␣ in control group subjects, but not in subjects with SCI. Conclusions: Individuals with SCI had more extensive basal and exercise-induced platelet activation and sP-selectin release than people without SCI. Moreover, strenuous arm exercise, which enhanced the release of prostacyclin in healthy subjects, failed to do so in those with SCI. Key Words: Exercise; Platelets; Prostacyclin; P-selectins; Rehabilitation; Spinal cord injuries. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
From the Department of Physical Therapy, Chang Gung University (Wang); and Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital (Yang, Wong), Taiwan, ROC. Accepted in revised form February 14, 2001. Supported by the National Science Council (grant no. NSC 88-2314-B-182-080). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Jong-Shyan Wang, PhD, Dept of Physical Therapy, Chang Gung University, 259 Wen-Hwa 1st Rd, Kwei-Shan, Tao-Yuan, Taiwan 333 ROC, e-mail:
[email protected]. 0003-9993/02/8302-6745$35.00/0 doi:10.1053/apmr.2002.28033
Arch Phys Med Rehabil Vol 83, February 2002
ANY INDIVIDUALS with spinal cord injury (SCI) die of cardiovascular disease. Platelets have been shown to M play an important role in the pathogenesis and progression of 1
cardiovascular diseases.2 Previous studies have suggested that the risk of primary cardiac arrest may be transiently increased during vigorous exercise.3,4 Our previous study showed that strenuous short-term exercise can enhance platelet function.5 Moreover, the effect of severe exercise tends to be more pronounced in people who are sedentary than in people who are active.5 Individuals with SCI may have a sedentary lifestyle because muscle strength and cardiopulmonary fitness progressively decrease, leading to further debilitation.6,7 In addition, individuals with lower limb paralysis because of SCI typically use their arms for wheelchair locomotion and other activities of daily living, as well as for exercise training and sports activities. However, how strenuous arm exercise effects platelet function in individuals with SCI remains unclear. We conducted this study to clarify the effect of strenuous arm exercise on platelet function in individuals with SCI. The in vitro assay of the functional activity of platelets was determined by the platelet adhesiveness on a tapered parallel-plate chamber and the platelet aggregability as evaluated by the percentage of reduction in a single platelet count.5 In addition, we studied P-selectin, a glycoprotein contained in the platelet alpha granules, from where it is mobilized to the cell surface after activation.8 Increased levels of plasma P-selectin have been observed in several cardiovascular diseases.9,10 Therefore, we also measured basal and exercise-induced plasma soluble P-selectin (sP-selectin) levels to reflect the functional status of platelets in patients with SCI. Prostacyclin (PGI2) is a potent antiplatelet agent.11 Although studies investigating healthy humans have indicated that shortterm exercise could enhance PGI2 release,12 there were no similar studies investigating individuals with SCI. In this study, we also determined urinary PGI2 metabolite levels to elucidate whether SCI affects basal and exercise-induced PGI2 release. METHODS Participants The protocol used in this study was reviewed and approved by an institutional review committee to protect the human rights of the participants. Two groups of participants were selected: 1 group was comprised of people who had SCI below the T10 level (the SCI group) and the other was comprised of people who did not have SCI (the control group). All participants gave their informed consent and understood the experimental procedures before they took part in the study. The 7 men and 3 women in the SCI group had SCI for at least 6 weeks; the basal characteristics and information about their lesions are listed in table 1. Ten healthy people of comparable age and gender who had not engaged in any regular physical activity for at least 1 year were selected as the control group; these people were 34.6 ⫾ 3.8 years old, were 165.4 ⫾ 2.6cm tall, and weighed 64.1 ⫾ 4.1kg. None of the SCI group had a history of significant cardiovascular, pulmonary diseases; musculoskeletal disability in upper limb; or urinary bladder inflam-
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EXERCISE AFFECTS PLATELETS IN SCI PATIENTS, Wang Table 1: Selected Characteristics Subjects With SCI Subject
A B C D E F G H I J
Gender
Male Male Male Female Male Male Female Female Male Male
Lesion Level
Age (y)
Weight (kg)
Height (cm)
Duration of Lesion (wk)
T11 T12 T12 T12 L1 L1 L1 L1 L2 L2
19 50 49 40 18 41 21 44 26 32
53.5 57.8 54.9 48.0 53.6 67.0 53.5 50.0 66.7 65.0
168 160 162 154 149 172 153 153 172 170
60.7 13.0 9.0 15.0 23.0 6.1 6.5 25.7 10.7 17.0
mation. None of the subjects had taken aspirin or other antiplatelet drugs for at least 2 weeks before this study. Exercise and Blood and Urine Collection Protocol All subjects completed the medical history form and physical activity questionnaire before coming to the laboratory to undergo a progressive arm exercise test on a System 2000 arm crank ergometer.a They arrived at 2:00 PM to participate in this study to avoid possible diurnal influence.13 After the subjects had rested 30 minutes, a blood sample was drawn from a forearm vein of each subject for baseline data of hematologic parameters and platelet function. Sodium citrate was used as an anticoagulant agent. Exercise began at 2:30 PM. The exercise protocol consisted of strenuous exercise up to peak oxygen consumption (VO2peak). The subjects started with 2 minutes of unloaded cranking, followed by a 10-W increment in workload every 2 minutes until they were exhausted. Immediately after exercise, another blood sample was collected to measure postexercise hematologic parameters and platelet function. All subjects provided urine samples before the exercise started and 1 hour after it ended. Subjects in the SCI group used a urine catheter. ˙ E), oxygen consumption Heart rate, minute ventilation (V ˙ O2), and carbon dioxide production (V ˙ CO2) were measured (V during the exercise by using an automated system.a These measurements were obtained as described previously.5 However, because it is difficult to accurately measure maximum ˙ O2 in an arm crank exercise in this study, VO2peak was V defined according to at least 3 of the following 4 criteria: (1) ˙ O2 was less than 2mL 䡠 kg⫺1 䡠 min⫺1 after at the increase of V least 2 minutes, (2) heart rate exceeded its predicted maximum, (3) the respiratory exchange ratio (RER) exceeded 1.10, and/or (4) venous lactate concentration exceeded 50mg/dL immediately after the exercise ended.14 Moreover, the ventilatory threshold was determined by at least 2 of the following 3 ˙ E/V ˙ O2 began to increase systematically withcriteria: (1) the V ˙ E/V ˙ CO2, (2) the end tidal out a corresponding increase in the V PO2 began to increase without a decrease in the end tidal PCO2, and/or (3) departure from linearity for minute ventilation.15 Platelet Adhesiveness A tapered parallel-plate chamber provided shear-stress values covering the entire physiologic range in human circulation; this chamber was used to assess platelet adhesiveness on fibrinogen-coated glass as described previously.5 The linear shear stress flow chamber consisted of 4 components: a stainless cover plate, a glass slide plate, a Teflon威 gasket, and a plastic distributor. Ten milliliters of blood samples was transferred into a polypropylene tube containing sodium citrate
(3.8g/dL; 1:9 volume of blood).b Platelet-rich plasma (PRP) was prepared by centrifugation at 1000rpm for 10 minutes at room temperature. Before the experiment started, a thoroughly cleaned glass plate was coated with 3mg/dL human fibrinogen.c After the chamber had been assembled, it was then placed on the stage of an inverted microscope, equipped with a capacitance coupled devicec video camera. The inlet of the chamber was connected to a perfusion system. PRP was gently infused into the chamber and kept there for 12 minutes to allow platelet settlement on the fibrinogen-coated surface. The flow chamber was then flushed with Tyrode-HEPES buffer (NaCl,c 0.128 mol/L and [mmol/L] KClc 2.7, MgCl2c 0.5, CaCl2c 2, NaHzPO4c .36, NaHCO3c 12, HEPESc 10; PH 7.4) for 5 minutes at a flow rate of .027mL/s, which provided the range of shear stress from 56 to 0 dyne/cm2. This flow chamber can generate a linear shear field with a constant shear stress gradient over the entire length of the chamber. Eight field locations along the center line were observed at intervals of 0.8cm from the downstream end with approximately no shear stress, and the number of remaining platelets per unit area (.16mm2) was counted at each location. A linear correlation between adherent platelets and local shear stress values was obtained, and the slope of this line was used as an index of platelet adhesiveness (ie, the less negative the slope, the greater the platelet adhesiveness). Platelet Aggregability Platelet aggregation induced by epinephrined was evaluated by the percentage of reduction in single platelet counts as described in a previous study.5 Ten milliliters of blood sample was transferred into a polypropylene tube containing sodium citrate. Platelet aggregation kinetics in PRP was measured with a platelet aggregometere after addition of various concentrations of epinephrine (ie, .25, 0.5, 1.0, 2.0, 4.0m in final concentration). After the optic density had reached a steady value for at least 1 minute, the test tube was then removed from the aggregometer and kept at rest for 90 minutes, allowing the sedimentation of platelet aggregates. Forty microliters of plasma was removed from the upper suspension of the PRP for single count. Results are expressed as a percentage of aggregated platelets to total platelets by using the following formula: 共single platelet count before inducers ⫺ single platelet count after inducers)/ (single platelet count before inducers) ⫻ 100%. The dose-response curves for epinephrine-induced platelet aggregation were obtained by logistic fitting. The geometric means of (epinephrine) ED50 were then analyzed. Arch Phys Med Rehabil Vol 83, February 2002
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EXERCISE AFFECTS PLATELETS IN SCI PATIENTS, Wang Table 2: Comparison of Exercise Performance Between Groups
Peak Exercise Wpeak (W) Time to exhaustion HRpeak (bpm) VEpeak (L/min) VO2peak (L/min) VO2peak (mL 䡠 kg 䡠 min) Peak O2 pulse (mL/beat) VCO2peak (L/min) RER Ventilatory Threshold W (W) HR (bpm) V˙E (L/min) V˙O2 (L/min) V˙O2 (mL 䡠 kg 䡠 min) O2 pulse (mL/beat) V˙CO2 (L/min) RER
Control
SCI
P
76.1 ⫾ 6.6 15.3 ⫾ 1.3 170 ⫾ 3 68.0 ⫾ 4.3 1.54 ⫾ 0.10 22.9 ⫾ 1.7 9.98 ⫾ 0.40 2.07 ⫾ 0.11 1.37 ⫾ 0.04
56.3 ⫾ 7.1 11.2 ⫾ 1.4 167 ⫾ 5 48.0 ⫾ 4.4 1.11 ⫾ 0.09 20.7 ⫾ 1.7 6.91 ⫾ 0.71 1.53 ⫾ 0.14 1.37 ⫾ 0.01
.0392 .0342 NS ⬍.0001 .0048 .0295 .0136 .0057 NS
33.5 ⫾ 3.7 108 ⫾ 5 19.4 ⫾ 2.0 .67 ⫾ 0.06 10.6 ⫾ 1.2 6.00 ⫾ 0.54 .68 ⫾ 0.09 1.01 ⫾ 0.03
22.5 ⫾ 2.81 113 ⫾ 7 16.3 ⫾ 1.5 .55 ⫾ 0.05 10.0 ⫾ 2.2 4.80 ⫾ 0.47 .56 ⫾ 0.06 1.01 ⫾ 0.03
.0308 NS NS NS NS .0424 NS NS
NOTE. Data are as mean ⫾ standard error. Abbreviation: HR, heart rate; VEpeak, peak minute ventilation; VCO2peak, peak
Plasma sP-Selectin Each blood sample was collected into a polypropylene tube containing sodium citrate (3.8g/dL; 1:9 volume of blood).b The plasma was obtained by centrifugation at 10,000g for 30 minutes at 4°C. Plasma sP-selectin was measured by using commercial kits.f Urinary 6-keto-prostaglandin F1␣ Because PGI2 has a short halflife, we measured their stable urinary metabolites, ie, 6-keto-prostaglandin F1␣ (6-keto PGF1␣).g These metabolites were measured by using commercial kits.g The concentrations of these substances were normalized with urinary creatinine levels, which were determined by a modified Jaffe alkaline picrate method.16 Statistics Data were expressed as mean ⫾ standard error of the mean. The statistical software package StatView®, version 4,h running on a Macintosh computer, was used to analyze the data. The differences of resting and postexercise between the control group and the SCI group were analyzed by 2-factorial analysis of variance followed by Tukey multiple comparison. Comparisons of exercise-induced changes between the control group and the SCI group were analyzed by the Student t test for unpaired samples. The association of measurements with other biochemical parameters was assessed by the Spearman rankcorrelation test. Differences were considered significant at P ⬍ .05. RESULTS Exercise Performance The cardiorespiratory response to peak arm exercise of subjects in the SCI and control groups are shown in table 2. SCI group results were significantly lower than the control group in the following tests: peak workload, time to exhaustion, peak minute ventilation, VO2peak, peak CO2 production, and peak O2 pulse. In addition, the SCI group also scored lower in exercise Arch Phys Med Rehabil Vol 83, February 2002
CO2
production; NS, not significant.
workload and O2 pulse at ventilatory threshold than the control group. These results imply that individuals with SCI cannot exercise as much and have less aerobic capacity than healthy individuals. Platelet Adhesiveness and Aggregability The platelet counts of SCI group subjects did not differ significantly from those of control subjects. Immediately after strenuous exercise, both groups showed increased platelet counts (control: rest, 284.1 ⫾ 8.5 ⫻ 109/L vs postexercise, 346.1 ⫾ 8.8 ⫻ 109/L, P ⬍ .05; SCI: rest, 275.4 ⫾ 7.4 ⫻ 109/L vs postexercise, 340.0 ⫾ 8.3 ⫻ 109/L, P ⬍ .05). The mean percentages of attached platelets at the locations at various shear stresses are presented in figure 1. Strenuous arm exercise increased platelet adhesiveness, indicated as the adhesive slope in both groups (fig 2; control: rest, ⫺1.409 ⫾ .056 vs postexercise, ⫺.999 ⫾ .070, P ⬍ .05; SCI: rest, ⫺.992 ⫾ .055 vs postexercise, ⫺.789 ⫾ .042, P ⬍ .05). However, the SCI group had remarkably greater platelet adhesiveness at resting and immediately after exercise than the control group (fig 2; P ⬍ .05). Dose responses of platelet aggregation induced by epinephrine are shown in figure 3. Strenuous arm exercise increased platelet aggregability, indicated as (epinephrine) ED50, in both groups (fig 2; P ⬍ .05). However, pre- and postexercise (epinephrine) ED50 in SCI group subjects were significantly lower compared with levels in control group subjects (fig 2; P ⬍ .05). Urinary 6-keto PGF1␣ and Plasma sP-Selectin As shown in figure 4, the level of plasma sP-selectin correlated negatively with the level of urinary 6-keto PGF1␣ at rest in the control and the SCI subjects. At rest, and after exercise, the SCI group had higher plasma P-selectin content but had lower urinary 6-keto PGF1␣ than the control group (fig 5). Moreover, strenuous arm exercise increased the level of plasma sP-selectin in the SCI group but not in the control group. In contrast, strenuous arm exercise increased the level of urinary 6-keto PGF1␣ in the control group but not in the SCI group (fig
EXERCISE AFFECTS PLATELETS IN SCI PATIENTS, Wang
Fig 1. The effect of strenuous arm exercise on platelet adhesiveness on fibrinogen coated-surface in the control group and the SCI group.
213
Fig 3. The effects of strenuous arm exercise on epinephrine-induced platelet aggregation in the control group and the SCI group.
5). In addition, the SCI group had higher exercise-induced change in plasma sP-selectin content but had lower exerciseinduced changes in urinary 6-keto PGF1␣ content than the control group (fig 6). DISCUSSION Study results lead to 2 observations: (1) subjects in the SCI group could not exercise as much and had less aerobic capacity than subjects in the control group, and (2) subjects in the SCI group had higher levels of platelet adhesiveness and aggregability in vitro, higher plasma sP-selectin content, but lower
Fig 2. Comparison of adhesive slope and (epinephrine) ED50 at rest and after exercise between the control group and the SCI group. Strenuous arm exercise increased platelet adhesiveness and aggregability in both groups. However, pre- and postexercise adhesiveness and aggregability in SCI group subjects were significantly lower compared with levels in control group subjects. *P < .05 (rest vs exercise); †P < .05 (control group vs SCI group).
Fig 4. Correlation between the levels of plasma sP-selectin and urinary 6-keto PGF1␣ (PG) at rest in the all subjects. (O, control subjects; ●, SCI subjects; C, creatinine).
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EXERCISE AFFECTS PLATELETS IN SCI PATIENTS, Wang
Fig 5. Comparison of (A) plasma sP-selectin and (B) urinary 6-keto PGF1␣ (PG) at rest and after exercise between the control group and the SCI group. *P < .05 (rest vs exercise); †P < .05 (control group vs SCI group).
urinary 6-keto PGF1␣ level than subjects in the control group. Moreover, results from our study indicated that in vitro platelet activation induced by epinephrine may be sensitized by strenuous arm exercise in all subjects, but only in the SCI group was in vivo P-selectin expression enhanced by exercise. The study
also found that strenuous exercise raised the level of urinary 6-keto PGF1␣ in control group subjects but not in subjects with SCI. Platelets play a pivotal role in the pathogenesis of thrombosis and atherosclerosis.2 Adhesion, aggregation, and secretion
Fig 6. Comparison of exercise-induced changes in (A) plasma P-selectin and (B) urinary 6-keto PGF1␣ (PG) between the control group and the SCI group. *P < .05 (rest vs exercise).
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EXERCISE AFFECTS PLATELETS IN SCI PATIENTS, Wang
are the major platelet reactions.2 In this study, our results showed that the platelet counts of SCI group subjects did not significantly differ from those of control subjects. However, various studies, including this one, found an increase in platelet counts, ranging from 18% to 80% immediately after treadmill, bicycle, or arm crank exercise.17,18 Despite the increase in platelet number, most studies regarding the effects of exercise on platelet functional behavior have been controversial. These discrepancies may be caused by different methodologic determinations in various studies.19,20 Those who measured platelet aggregation with turbidometry and did not correct for the postexercise increase in platelet counts showed an increase in the extent of platelet aggregation after strenuous exercise,17,21 whereas those who used specimens with a standardized platelet count showed no change in platelet aggregation after exercise.20,22 A possible explanation for the discrepancy is that the turbidity changes in PRP reflect primarily the formation of large platelet aggregates, which is more favored under high platelet density.23 In recent studies, the platelet aggregability, measured by the disappearance of single platelets, was enhanced by adenosine diphospate after maximal bicycle exercise in healthy men.22,24 The study indicated that although strenuous arm exercise increased the platelet aggregation–induced epinephrine in both study groups, when subjects were at rest and after they had exercised, the platelet aggregability in the SCI group was greater than that in the control group. The finding was consistent with the previous results.22,24 In addition, similar results were observed in resting and postexercise platelet adhesiveness. The evidence suggests that, although in vitro platelet adhesiveness and aggregability may be increased by strenuous arm exercise in both groups, in vitro platelet activation induced by biomaterials is more extensive in individuals with SCI than in healthy individuals. However, how the various intensities of acute exercise affect platelet function in individual with SCI is still unclear. Our previous study5 with healthy men and men with stable angina showed that platelet function may be sensitized by strenuous exercise and may be suppressed by moderate exercise. To investigate the different effects of strenuous exercise and moderate exercise on platelet function in individuals with SCI, a further study is ongoing. Previous studies show that severe exercise can increase epinephrine release25 and that individuals with SCI below T10 show sympathoadrenal activity similar to the noninjured, whereas those with injuries higher than T6 do not.26 Because SCI group subjects in this study had SCI below T10 level, the release of exercise-induced epinephrine should be similar in both groups. However, a previous study indicated that there was a supersensitivity of platelet ␣2-adrenoreceptor in SCI patients.27 This study indicated that platelet aggregation by epinephrine was higher in SCI subjects than in healthy subjects, which is consistent with the findings in the previous study.27 In addition, our recent study has suggested that strenuous, acute exercise augments the risk of major vascular thrombotic events partially because severe exercise may increase endogenous catecholamine (ie, epinephrine, norepinephrine), which in turn may augment platelet activation.28 Acting through ␣2-adrenoreceptors, epinephrine may enhance the opening of glycoprotein IIb/IIIa binding sites for fibrinogen in the presence of adenosine diphosphate and that fibrinogen binding to the active form of fibrinogen receptor would produce platelet aggregation.29 Therefore, the mechanisms changing platelet activation induced by strenuous arm crank exercises in both groups may be caused, in part, by the increased endogenous release of epinephrine to enhance the ability of platelet activation.28
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In the in vivo experiment, the SCI group had higher plasma sP-selectin content than the control group. Human platelets contain the soluble form of P-selectin,8 and an increase in plasma sP-selectin can be observed in several diseases associated with platelet activation.9,10 It can be hypothesized that the platelets could also contribute to the increase in plasma sPselectin observed in the SCI patients. Therefore, the results in this study suggest that the SCI group had more in vivo platelet activation than the control group. Moreover, strenuous arm exercise raised the level of plasma sP-selectin in the SCI group but not in the control group. These results imply that strenuous arm exercise might evoke in vivo platelet activation in the SCI group but not in the control group. The underlying mechanisms decreasing PGI2 level in the SCI subjects remain unclear. Although 6-keto PGF1␣ concentration in cerebrospinal fluid and in the spinal cord was higher at the acute stage of injury, it subsequently returned to the same level as the controls at the chronic stage in previous studies.30,31 However, this study found that subjects in the SCI group had a lower urinary 6-keto PGF1␣ level than subjects in the control group. Langille and O’Donnell32 indicated that a chronic decrease in blood flow led to a reduction in blood vessel diameter, and this change appeared to be mediated by low levels of endothelium-derived relaxing factors, such as PGI2 and nitric oxide. Individuals with SCI may experience decreased blood flow or even stasis because of impairment of sympathetically mediated vasoregulatory capacity and lack of the muscle pumping action in immobilization of the lower limb.33 Therefore, the phenomenon of decreased blood flow may explain the lower level of PGI2 found in individuals with chronic SCI. Some studies have reported that PGI2 may inhibit platelet activity.11 In this study, subjects with SCI had higher plasma sP-selectin content than subjects without SCI. In addition, previous reports found that acute exercise could enhance the release of PGI2 in healthy humans.12 However, this study shows that strenuous arm exercise enhanced the level of urinary 6-keto PGF1␣ in the control group but not in the SCI group. This implies that individuals with SCI might have a greater extent of the severe exercise-induced platelet activation by diminishing PGI2 release enhanced by exercising, which, in turn, increases the predisposition toward platelet hyperactivity. CONCLUSION Individuals with SCI had a greater extent of platelet activation than healthy individuals. Strenuous arm crank exercise may sensitize in vitro platelet adhesiveness on fibrinogencoated surfaces and platelet aggregation induced by epinephrine in all subjects, but in vivo sP-selectin expression may be enhanced by this exercise only in the SCI group. Moreover, strenuous arm exercise, which enhanced the release of prostacyclin in subjects in the control group, failed to do so in those in the SCI group. Therefore, the risk of vigorous exercise evoking major vascular thrombotic events tends to be more pronounced in people with SCI than in healthy people. References 1. Yekutiel M, Brooks ME, Ohry A, Yarom J, Carel R. The prevalence of hypertension, ischaemic heart disease and diabetes in traumatic spinal cord injured patients and amputees. Paraplegia 1989;27:58-62. 2. Wolf N. Thrombosis and arteriosclerosis. Br Med Bull 1978;34: 137-42. 3. Siscovick DS, Weiss NS, Fletcher RH, Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984;311:874-7. Arch Phys Med Rehabil Vol 83, February 2002
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4. Corrado D, Thiene G, Nava A, Rossi L, Pennelli N. Sudden death in young competitive athletes: clinicopathological correlations in 22 cases. Am J Med 1990;89:588-96. 5. Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen H-I. Effects of strenuous exercise and moderate exercise on platelet function in males. Circulation 1994;90:2877-85. 6. Hoffman MD. Cardiorespiratory fitness and training in quadriplegics and paraplegics. Sport Med 1986;3:312-30. 7. Hopman MT, Dueck C, Monroe M, Philips WT, Skinner JS. Limits to maximal performance in individuals with spinal cord injury. Int J Sports Med 1998;19:98-103. 8. Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha-granule membrance protein (GMP 140) is expressed to plasma membrance after activation. J Cell Biol 1985; 101:880-6. 9. Ikeda H, Takajo Y, Ichiki K, et al. increased soluble form of P-selectin in patients with unstable angina. Circulation 1995;92: 1693-6. 10. Kaikita K, Ogawa H, Yasue H, et al. Soluble P-selectin in released into the coronary circulation after coronary spasm. Circulation 1995;92:1726-30. 11. Moncada S, Vane J. Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N Engl J Med 1979;300:1142-7. 12. Todd MK, Goldfarb AH, Boyer BT. Effect of exercise intensity on 6-keto-PGF1␣, TXB2, and 6-keto-PGF1␣/TXB2 ratios. Thromb Res 1992;65:487-93. 13. Tofler GH, Brezinski D, Schafer AI, et al. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987;316: 1514-8. 14. Taylor HL, Buskirk E, Heuschel A. Maximal oxygen intake as an objective measurement of cardiorespiratory performance. J Appl Physiol 1955;8:73-80. 15. Wasserman K, Whipp BJ, Koyal SN, Beaver WL. Anaerobic threshold and respiratory gas exchange during exercise. J Appl Physiol 1973;35:236-43. 16. Larsin K. Creatinine assay by a reaction-kinetic approach. Clin Chem Acta 1972;41:209-17. 17. Warlow CP, Ogston D. Effect of exercise on platelet count, adhesion, and aggregation. Acta Haematol 1974;54:47-52. 18. Chen HI, Tang YR, Wu HJ, Jen CJ. Effects of acute exercise on bleeding time, bleeding amount and blood cell count: a comparative study. Thromb Res 1989;55:503-10. 19. Collwell JA. Effects of exercise on platelet function, coagulation, and fibrinolysis. Diabetes Metab Rev 1986;1:501-12. 20. Bourey RE, Stantoro SA. Interactions of exercise, coagulation, platelets, and fibrinolsis: a brief review. Med Sci Sports Exerc 1988;20:439-46.
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21. Dimitriadou C, Dessypis A, Louizou C, Mandalaki T. Marathon run II: effects on platelet aggregation. Thromb Haemost 1977;37: 451-5. 22. Hendra TJ, Oughton J, Smith CC, Yudkin DJ. Exercise-induced changes in platelet aggregation: a comparison of whole blood and platelet rich plasma techniques. Thromb Res 1988;52:443-51. 23. Frojmovic MM, Milton JG, Duchastel A. Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from turbidometrically measured aggregation. J Lab Clin Med 1983;101:964-76. 24. Piret A, Niset G, Depress E, et al. Increase platelet aggregability and prostacylin biosynthesis induced by intense physical exercise. Thromb Res 1990;57;685-95. 25. Dimsdale J, Moss J. Plasma catecholamine in stress and exercise. JAMA 1980;243:340-2. 26. Munro AF, Robinson R. The catecholamine content of the peripheral plasma in human subjects with complete transverse lesions of spinal cord. J Physiol 1960;154:244-53. 27. Senard JM, Arias A, Berlan M, Tran MA, Rascol A, Montastruc JL. Pharmacological evidence of alpha 1- and alpha 2-adrenergic supersensitivity in orthostatic hypotension due to spinal cord injury: a case report. Eur J Clin Pharmacol 1991;41:593-6. 28. Wang JS, Cheng LJ. The effect of strenuous acute exercise on ␣2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 1999;19:1559-65. 29. Steen VM, Holmsen H, Aarbakke G. The platelet stimulating effect of adrenaline through ␣2-adrenergic receptors requires simultaneous activation by a true stimulatory platelet agonist. Thromb Haemost 1993;70:506-13. 30. Mitsuhashi T, Ikata T, Morimoto K, Tonai T, Katoh S. Increased production of eicosanoid, TXA2, PGI2 and LTC4 in experimental spinal cord injuries. Paraplegia 1994;32:524-30. 31. Nishisho T, Tonai T, Tamura Y, Ikata T. Experimental and clinical studies of eicosanoids in cerebrospinal fluid after spinal cord injury. Neurosurgery 1996;39:950-6. 32. Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1988;231:405-7. 33. Hopman MT, Verheijen PH, Binkhorst RA. Volume changes in the legs of paraplegic subjects during arm exercise. J Appl Physiol 1993:75:2079-83. Suppliers a. Medical Graphic Corp, 350 Oak Grove Pkwy, St. Paul, MN 55127. b. J.T. Baker Inc, 222 Red School Ln, Phillipsburg, NJ 08865. c. Minitron Enterprise Co, Ltd, No. 3, Wu-Kung 5 Rd, Taipei, Taiwan. d. Sigma Chemical Co, PO Box 14508, St. Louis, MO 63178. e. Model 1020B; Ion-Trace Inc, 115 Heatherise Dr, Scarborough, Ont MIW 1T6, Canada. f. R&D Systems Inc, 617 McKinley P1 NE, Minneapolis, MN 55413. g. Cayman Chemical Co, 690 KMS P1, Ann Arbor, MI 48108. h. SAS Institute Inc, SAS Campus Dr, Cary, NC 27513.
