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

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 <0.05). One day after withdrawal, the rise in heart rate with exercise or tilt was slightly increased from values before propranolol therapy. Two days after withdrawal of propranolol the mean peak heart rate during exercise (165 beats/min) was 12 beats/min higher (p <0.01) than the value before propranolol. On this same day heart rate increased more after tilt without medication (+6 beats/min, p <0.05) and more after tilt following vagal blockade (+8 beats/min, p <0.02) than before treatment with propranolol. Seven days after propranolol withdrawal, heart rate responses to exercise or tilt remained increased. Isoproterenol-induced heart rate responses (5 to 40 ng/kg per min, n = 14), white blood cell beta receptor function (cyclic adenosine monophosphate production after isoproterenol and ³H-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.