Shortened platelet survival time and enhanced heart rate responses after abrupt withdrawal of propranolol from normal subjects.

Abstract Although clinical observations suggest that abrupt discontinuation of propranolol therapy may precipitate myocardial ischemia and infarction in patients with coronary occlusive disease, the physiologic consequences of propranolol withdrawal are not fully understood. Platelet survival times and heart rate responses to exercise, upright tilt and isoproterenol were therefore examined in 14 normal subjects before and after abrupt withdrawal of propranolol. Propranolol, 80 to 240 mg/day, was given for 24 to 79 days; its effect was confirmed by a lower heart rate during exercise and during infusion of isoproterenol. In 10 subjects, the mean survival time of chromium-51-tagged blood platelets decreased from 10.0 days before propranolol to 7.8 days after its withdrawal (p 3 H-I-dihydroalprenolol binding, n = 9) and plasma norepinephrine values at rest and during exercise (n = 7) were each unaltered after propranolol. The results suggest that abrupt withdrawal of propranolol is accompanied by a shortening of platelet survival and enhancement of sympathetically mediated reflex increases in heart rate. These changes may each play a role in the increased incidence of ischemic episodes observed after withdrawal of propranolol from patients with coronary occlusive disease. However, the number of beta receptors and their sensitivity to adrenergic agonists do not seem to be changed uniformly after abrupt withdrawal of propranolol.