EFFICACY OF A BETA-ADRENERGIC-RECEPTOR ANTAGONIST, PROPRANOLOL, IN PREVENTING ISCHEMIC VENTRICULAR-FIBRILLATION - DEPENDENCE ON HEART-RATE AND ISCHEMIA DURATION

Objectives: To investigate the prevention of ventricular fibrillation with a P-adrenergic receptor (P-AR) antagonist in anaesthetized, open- chest pigs in a model of ischaemia, intended to reproduce what happens either in anginal attack or in the first hour of infarction.Methods: Ventricular fibrillation threshold (VFT) was determined with trains of diastolic stimuli of 100 ms duration delivered by a subepicardial ele ctrode inserted in the area subjected to ischaemia. Ischaemia was obta ined by the complete occlusion of the left anterior descending coronar y artery, either near its origin during brief but increasing periods ( 30, 60, 90, 120, 150, 180, 240, 300 s) or half-way from its origin for a much longer time (more than 60 min). Results: During transient prox imal occlusion and isoprenaline infusion (0.25 mu g/kg/min), propranol ol (50 mu g/kg plus 2 mu g/kg/min) attenuated both tachycardia and the fall in VFT to 0 mA. The shortening of MAP duration accompanying depo larization of the fibres was concurrently slowed down, and time to fib rillation prolonged (122 +/- 15 to 262 +/- 14s, p < 0.001). In the abs ence of isoprenaline infusion, propranolol exerted similar effects, bu t to a lesser degree, in proportion to heart rate dependent on sympath etic activity. In contrast, it became unable to raise VFT before and d uring ischaemia, when heart rate was kept constant by pacing. After pe rsistent midportion occlusion, significant differences in VFT were fou nd only at the 5th min, depending on whether heart rate was accelerate d by isoprenaline (0.8 +/- 0.2 mA), left normal (1.8 +/- 0.3 mA) or sl owed down by propranolol (1.6 +/- 0.3 mA). Later on. especially after 15 and 25 min of ischaemia, VFT, which was below 1.0 mA, did not appea r to be influenced by the activation or blockade of beta-ARs: spontane ous fibrillations were observed in the same number in this period with or without the administration of propranolol. Beyond 30 min after occ lusion, the rise in VFT, subsequent to the first irreversible cell dam age, also occurred in the same way.Conclusions: The prevention of isch aemic ventricular fibrillation by a P-AR antagonist, judged from VFT, is easily checked experimentally when ischaemia is only transitory, es pecially if sympathetic activity is high. The maintenance of VFT at a relatively high level is essentially related to the depressant effect on the sinus rate. The same animal model does not give support to an e ffective protection in the first hour of infarction. However, the cont rol of heart rate may also be beneficial in these circumstances by att enuating systemic haemodynamic disorders. (C) 1998 Elsevier Science B. V.