COMPARATIVE EFFECTS OF IDAZOXAN, PRAZOSIN, AND YOHIMBINE ON CORONARY LIGATION-INDUCED ARRHYTHMIAS IN SPONTANEOUSLY HYPERTENSIVE RATS

We investigated whether certain drugs with alpha-adrenergic antagonist activity display anti-arrhythmic effects in hypertensive animals subj ected to acute coronary artery ligation. The left anterior descending coronary artery (LAD) was ligated in open-chest pentobarbital-anesthet ized spontaneously hypertensive rats (SHR); arrhythmias were subsequen tly recorded for 30 min. Drugs were administered intravenously, (i.v.) 5 min before ligation. The effects of yohimbine and idazoxan were com pared with those of prazosin. Prazosin (100 mu g/kg) increased the occ urrence of ventricular tachycardia (VT). In contrast, yohimbine 1.6 mg /kg decreased both the occurrence and the duration of VT and the occur rence and the duration of ventricular fibrillation, (VF). The results obtained with idazoxan 1 mg/kg were similar to those with yohimbine. T he ECG alterations induced by coronary artery ligation in rats treated with yohimbine and idazoxan were more pronounced than in controls and in rats treated with prazosin, suggesting that the antiarrhythmic eff ects observed were not mediated by antiischemic activity. The protecti ve effects against ligation-induced arrhythmias were preceded by a hyp otensive effect and a decrease in the rate-pressure product in yohimbi ne-treated but not in idazoxan-treated animals. In rats treated with p razosin, more arrhythmic events were observed, although hemodynamics w ere similar to those in rats treated with yohimbine. Our results sugge st that the yohimbine-induced antiarrhythmic action is not due to an a lteration of conduction or repolarization rates. In this model, yohimb ine and idazoxan appear to protect against ligation-induced arrhythmia s. These data suggest that drugs with oi-adrenergic properties might i nfluence the nervous drive to the heart in SHR with cardiac ischemia. However, further investigations are needed to ascertain whether the ol -adrenoceptor blockade participates in this effect.