1. Abrupt termination of chronic propranolol therapy has been suggested to cause a ‘rebound’ phenomenon. To investigate this possibility guinea pigs were given propranolol orally for 21 days.
2. At various times over a 10 day period after the last dose hearts were removed and subjected to aerobic perfusion, ischaemia and reperfusion. Rhythm disturbances were measured and compared with corresponding values in control hearts from the control untreated animals.
3. Three to 6 days after termination of drug administration a pronounced increase in myocardial electrical instability was observed. During pre-ischaemic aerobic perfusion the incidence of arrhythmias was increased and during reperfusion the incidence of ventricular fibrillation rose dramatically.