VULNERABILITY TO VENTRICULAR-FIBRILLATION RELATED TO ISCHEMIA - COMPARISON OF THE ACUTE EFFECTS OF BETA-BLOCKERS AND CALCIUM-ANTAGONISTS

A comparative evaluation of beta-blockers and calcium antagonists as p rotective agents against ventricular fibrillation related to myocardia l ischaemia, was attempted in the pig heart in situ of anaesthetized, open-chest animals, subjected to a temporary complete occlusion of the left anterior descending coronary artery near its origin. This occlus ion resulted in fibrillation occurring after a time depending on the v ulnerability to the fibrillatory process. As this time to onset of fib rillation does normally not exceed a few minutes, its determination co uld be achieved repeatedly in the course of an experiment, in the abse nce and presence of drugs such as beta-blockers and calcium antagonist s. When propranolol (0.05 mg/kg, i.v.) and verapamil (0.05 mg/kg, i.v. ) abolished tachycardia produced by isoproterenol (0.25 mug/kg/min),. the triggering of fibrillation was delayed in either case: in animals under atrial pacing at a rate close to the sinus rate on each determin ation, time to fibrillation was prolonged from about 160 to 400 sec by propranolol and from 160 to 640 sec by verapamil, with a return to co ntrol values within 60 min. Under ventricular pacing at a constant hig h rate (180 beats/min), no change was observed in time to fibrillation after propranolol (0.025 or 0.050 mg/kg), whereas verapamil, in the s ame conditions and in the same doses, multiplied this time by about 4 and 6, respectively. Consequently, propranolol and verapamil are likel y to protect against fibrillation immediately after i.v. injection, bu t the protection due to propranolol is only indirect and a consequence of bradycardia which tends to increase the polarization of the muscul ar fibres, whereas verapamil adds to the same influence a direct preve ntive action by avoiding a cellular calcium overload in these fibres, which is responsible for the depolarization and fluctuations of their membrane potential.