CARDIAC BETA-ADRENOCEPTOR ACTIVATION AND VENTRICULAR-FIBRILLATION UNDER NORMAL AND ISCHEMIC CONDITIONS

Objectives: To investigate the role of ventricular and atrial beta-adr enoceptor activation by isoprenaline in the genesis of rhythm disorder s and risk of fibrillation in the healthy or ischaemic heart. Methods: The study was performed in anaesthetized, open-chest pigs. Electrical fibrillation threshold (EFT) of the ventricles was measured with trai ns of diastolic stimuli of 100 ms duration synchronized with respect t o the R-waves and delivered to the myocardium by a subepicardial elect rode introduced into the area which could be subjected to ischaemia. M onophasic action potential (MAP) and effective refractory period (ERP) were recorded in the same area. Ischaemia was obtained by complete oc clusion of the left anterior descending coronary artery near its origi n during increasing periods (30, 60, 90, 120, 150, 180, 240 s). Result s: At a rate varying according to the action exerted by isoprenaline o n the sinus rate, EFT decreased by about 30% in the healthy heart duri ng the infusion of 0.5 mu g/kg/min isoprenaline under the influence of the acceleration of cardiac beats. In the ischaemic heart, sinus tach ycardia accelerated the fall in EFT and the reduction in MAP duration and resulted sooner in spontaneous ventricular fibrillation. During ve ntricular pacing at a constant rate of 200 beats/min, isoprenaline rai sed EET by nearly 80% in the absence of ischaemia, but this rise was a bolished by ischaemia, at least of no-flow type. Conclusions: Tachycar dia produced by activation of atrial adrenoceptors decreases EFT in th e healthy heart and aggravates its fall in the ischaemic heart. Ventri cular adrenoceptor activation counteracts the EFT fall related to tach ycardia in the healthy heart, but not in the ischaemic heart. Therefor e, the protection against ischaemic fibrillation due to beta-blockers would be essentially attributable to their action on the sinus node.