Platelet factor 4 release during exercise in patients with coronary artery disease.
Many recent studies provide evidence that increased platelet activation occurs in a significant number of patients with atherosclerotic coronary artery disease. The mechanisms responsible for this activation are unknown, although there have been studies suggesting a correlation with abnormal lipoproteinemia, acute myocardial infarction, unstable angina, and exercise-induced myocardial ischemia. We studied 84 patients undergoing standardized treadmill exercise using either a Bruce [N = 63] or symptom-limited Naughton protocol [N = 21]. In contrast to ten healthy volunteer subjects, the patient group demonstrated a significant increase in plasma concentrations of platelet factor 4 [PF4] between pre- and postexercise blood samples confirming earlier reports of exercise-induced platelet activation and secretion. As with previous studies, however, only a subset of patients demonstrated this response. When the entire group was analyzed for the presence or absence of electrocardiographic ischemic changes and the presence of documented versus suspected coronary artery occlusions, there were no differences noted between groups that explained the variable responses measured. However, there was a significant difference between patient groups when analyzed by whether or not they were being treated with beta-blocking agents. Patients who were being treated with propranolol or one of the longer-acting beta-blocking agents did not have a significant increase in plasma PF4 following exercise, in contrast to patients who were not beta-blocked. Plasma concentrations of epinephrine, norepinephrine, and lactic acid were measured in 49 patients and all normal subjects. There was no correlation between the changes in plasma PF4 concentrations and any of these three variables, suggesting that platelet activation was not occurring through direct platelet activation by circulating catecholamines. This study provides further evidence that there is a subset of CAD patients with platelet hyperactivity. This is the first time that beta-blockade has been demonstrated to modify this platelet response. The effectiveness of beta-blocking agents in CAD may be in part related to their antiplatelet effect.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism*; D004562:Electrocardiography; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000096:biosynthesis*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D007773:Lactates; D019344:Lactic Acid; D010978:Platelet Factor 4