Effect of strenuous exercise on platelet activation state and reactivity.

BACKGROUND: It has been hypothesized that platelets are activated, or made more activatible, by strenuous exercise and that these changes may play a role in the genesis of exercise-induced coronary ischemia. Previous studies have yielded conflicting results but have used assays (eg, platelet aggregation, plasma platelet factor 4, and plasma beta-thromboglobulin) that are subject to methodological problems. METHODS AND RESULTS: In the present study, a whole blood flow cytometric method was used to study the platelet activation state and reactivity of 12 physically active and 12 sedentary individuals before and after standardized treadmill exercise testing. The peptide gly-pro-arg-pro (GPRP) was included in this assay to prevent fibrin polymerization and platelet aggregation, thus allowing the measurement of the reactivity to thrombin of individual platelets in the physiological milieu of whole blood. A panel of fluorescent-labeled monoclonal antibodies was used to monitor activation-dependent platelet surface changes: downregulation of glycoprotein (GP) Ib (6D1) and upregulation of GMP-140 (S12), the GPIIb-IIIa complex (PAC1), and GPIV (OKM5). In samples obtained before exercise, platelets not exposed to thrombin showed no evidence of in vitro activation. In the sedentary subjects, exercise caused a consistent and significant augmentation of the platelet activation state and reactivity as judged by the binding of 6D1 in the presence of thrombin 0.05 U/mL (P < .001), 0.005 U/mL (P = .001), and 0 U/mL (P = .004) and by the binding of OKM5 in the presence of thrombin 0.05 U/mL (P < .001), 0.005 U/mL (P = .029), and 0 U/mL (P = .035). Exercise increased the binding of PAC1 at only a single thrombin concentration (0.005 U/mL, P = .027) and did not alter the binding of S12 at any thrombin concentration. In contrast, in the physically active subjects, exercise failed to cause a consistent alteration in either platelet activation state or platelet reactivity. No significant differences were found between the 12 male and 12 female volunteers. CONCLUSIONS: Strenuous exercise in sedentary subjects but not physically active subjects resulted in both platelet activation and platelet hyperreactivity. These changes were more readily detected with monoclonal antibodies directed against GPIb (6D1) and, to a lesser extent, GPIV (OKM5) rather than those directed against the GPIIb-IIIa complex (PAC1) and GMP-140 (S12). Platelet activation by thrombin, generally regarded as the most physiologically important agonist, can be studied in whole blood in a clinical setting through the use of the peptide GPRP.

Cardiovascular evaluation after withdrawal from chronic alcohol or cocaine-alcohol abuse.

Alcohol ingestion commonly accompanies cocaine abuse, but the effects of chronic cocaine-alcohol abuse on the circulation are undefined. Therefore, to test for evidence of cocaine-alcohol cardiac dysfunction and interference with cardiovascular nervous system reflexes, 10 normal volunteers (group I), 8 asymptomatic alcoholic patients (group II), and 15 age matched, asymptomatic cocaine and alcohol abusers (group III) underwent screening two-dimensional echocardiography, electrocardiography, a series of autonomic nervous system tests, and upright bicycle exercises. Echocardiographic indices did not differ among groups. R wave voltage was increased in group III, probably primarily due to a smaller body surface area. Heart rate (HR) and/or systolic blood pressure (SBP) responses to 60 degree tilt and to hyperventilation differed in group III (decreased HR response, while SBP increased inappropriately). Despite excellent exercise tolerance, HR response to exercise in group III (compared to group I) was decreased. These results suggest impairment of certain autonomic nervous system reflexes and, possibly, sinus node dysfunction from cocaine-alcohol abuse.

Effects of methyldopa on psychometric performance.

Double-blind, crossover comparisons of methyldopa with placebo were performed in 16 patients with mild to moderate hypertension. Methyldopa (250 mg tid) for 14 days significantly reduced blood pressure, impaired card-sorting time and digital symbol substitution score, and caused trends for impairment of other psychometric tests. Effects of practice were greater than those of treatment on all tests other than card sorting, although no interaction between treatment and practice was seen. Continued dosage impairs psychometric performance, but practice effect is a major confounder. Simple crossover studies are inadequate for detecting moderate drug effects on intellectual performance.

Is valve replacement indicated in asymptomatic patients with aortic stenosis or aortic regurgitation?

With rare exceptions, aortic valve replacement should be performed in all symptomatic patients with hemodynamically significant aortic stenosis; however, the asymptomatic patient requires a difficult risk-benefit analysis. In most asymptomatic patients the risks of aortic valve replacement outweigh the risks of conservative therapy and careful follow-up. Symptomatic patients with chronic aortic regurgitation should undergo aortic valve replacement. Asymptomatic patients with normal left ventricular function are not surgical candidates, but aortic valve replacement should be performed in most patients with reliable evidence for left ventricle dysfunction, even if symptoms are not yet present.

Cardiogenic brain embolism and lupus anticoagulant.

The lupus anticoagulant, an acquired immunoglobulin associated with an increased tendency for thrombosis, has been linked to the occurrence of cerebral ischemia presumably related to in situ thrombosis. Cardioembolic cerebral ischemic events have rarely been reported. We encountered 2 patients with focal cerebral ischemia, substantial mitral valvular masses, and a circulating lupus anticoagulant. In each, diagnostic evaluation supported a cardioembolic etiology. These findings illustrate the need for evaluating patients with cerebral ischemic events for a cardioembolic source when a circulating lupus anticoagulant is present.

Response to exercise after withdrawal from chronic alcoholism.

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.

The effect of once-daily minoxidil on blood pressure and plasma lipids.

Once-daily minoxidil administration was added to the treatment regimen of 11 patients with hypertension that was inadequately controlled by nadolol 160 mg and chlorthalidone 50 mg given once daily. Additional diuretic therapy was needed by five patients. During treatment without minoxidil and at three and six months of maintenance minoxidil therapy, respectively, 24-hour postdose supine blood pressure fell significantly (P less than .01) from 142 +/- 19/96 +/- 6 mm Hg to 132 +/- 16/87 +/- 4 and 131 +/- 12/87 +/- 4 mm Hg, and home recordings showed that minoxidil induced a mean increase of about 5 beats/min in heart rate. Resting plasma renin activity was not significantly altered. High-density lipoprotein (HDL) cholesterol increased from 31.6 +/- 9.9 to 35.2 +/- 10.9 mg/dL (P less than .05) and to 34.4 +/- 11.3 mg/dL (NS), and low-density lipoprotein (LDL) cholesterol decreased from 146 +/- 36 to 136 +/- 32 mg/dL (P less than .05) and to 126 +/- 35 mg/dL (P less than .01) over the same periods. At six months, approximately 20% changes in ratios of HDL cholesterol to either LDL or total cholesterol were seen. These changes occurred despite a three-pound mean increase in body weight (P less than .05); these alterations are potentially beneficial in terms of reducing the estimated risk of coronary artery disease.

Anomalous origin of the posterior descending artery from the first septal perforator.

We describe a patient with an unusual coronary anatomic variant in which the first septal perforator gives rise to the posterior descending artery. The angiographic features and clinical recognition of this anomaly are reviewed.

Management of oral anticoagulant therapy. Experience with an anticoagulation clinic.

The experience acquired in an anticoagulation clinic during 4 1/2 years is reviewed to demonstrate the effectiveness of such a clinic and to provide the practicing physician with guidelines for managing outpatient oral anticoagulation therapy. The experience is based on anticoagulant therapy in 141 patients during 1,264 patient-months. The patient population is characterized and aspects of management are explored, such as the incidence of major and minor complications (5% and 18% per treatment course, respectively), failure rate, and adequacy of therapy control. Guidelines concerning patient education, prothrombin time control, and other management suggestions are also given. This study, which compares favorably with others, is intended to aid the practicing physician and improve management of outpatient anticoagulation therapy.