Ischemia- and reperfusion-induced arrhythmias in conscious rats. Studies with prazosin and atenolol.

A conscious rat system has been developed to investigate the ability of alpha- and beta-adrenoceptor blocking agents to modify the severity of ischemia- and reperfusion-induced arrhythmias. Ischemia-induced arrhythmias were studied during a 30 min period of occlusion of the left anterior descending (LAD) coronary artery, and 100% of control animals (n = 24) exhibited ventricular tachycardia and 63% ventricular fibrillation. Beta-adrenoceptor blockade with atenolol (1 mg/kg body weight) significantly reduced the incidence of ventricular fibrillation to 17% (p less than 0.05). In contrast, alpha-adrenoceptor blockade with prazosin (0.01, 0.1 or 1 mg/kg body weight) failed to reduce the incidence of arrhythmias and actually increased mortality. This higher mortality with prazosin was associated with bradyarrhythmias. Administration of atenolol (1 mg/kg body weight) also reduced the incidence of reperfusion-induced ventricular fibrillation after a 5 min period of ischemia from 100% to 58% (p less than 0.05). Prazosin could not be tested due to the high mortality during coronary occlusion. Autopsy studies of hearts from the control, atenolol and prazosin groups indicated that all groups had similar occluded zone volumes. In conclusion, in conscious rats beta-blockade with atenolol reduced the incidence of both ischemia- and reperfusion-induced arrhythmias, whereas alpha-blockade with prazosin at the 3 doses studied failed to exert a protective effect and actually increased mortality.