Abstract
We investigated whether certain drugs with alpha-adrenergic antagonist activity display anti-arrhythmic effects in hypertensive animals subjected to acute coronary artery ligation. The left anterior descending coronary artery (LAD) was ligated in open-chest pentobarbital-anesthetized spontaneously hypertensive rats (SHR); arrhythmias were subsequently recorded for 30 min. Drugs were administered intravenously, (i.v.) 5 min before ligation. The effects of yohimbine and idazoxan were compared with those of prazosin. Prazosin (100 mu g/kg) increased the occurrence of ventricular tachycardia (VT). In contrast, yohimbine 1.6 mg/kg decreased both the occurrence and the duration of VT and the occurrence and the duration of ventricular fibrillation, (VF). The results obtained with idazoxan 1 mg/kg were similar to those with yohimbine. The 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 effects observed were not mediated by antiischemic activity. The protective effects against ligation-induced arrhythmias were preceded by a hypotensive effect and a decrease in the rate-pressure product in yohimbine-treated but not in idazoxan-treated animals. In rats treated with prazosin, more arrhythmic events were observed, although hemodynamics were similar to those in rats treated with yohimbine. Our results suggest that the yohimbine-induced antiarrhythmic action is not due to an alteration of conduction or repolarization rates. In this model, yohimbine and idazoxan appear to protect against ligation-induced arrhythmias. These data suggest that drugs with alpha-adrenergic properties might influence the nervous drive to the heart in SHR with cardiac ischemia. However, further investigations are needed to ascertain whether the alpha-adrenoceptor blockade participates in this effect.
Published Version
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