The effect of beta-adrenoceptor blockade and of thromboxane synthetase inhibition, alone and in combination, on arrhythmias resulting from myocardial ischemia.

The effects of pretreatment with metoprolol (2 mg/kg, i.v.), UK 38,485 (5 mg/kg, i.v.), and a combination of the two drugs were examined on early (0-0.5/hr) and late (0.5-4 hr) ischemic arrhythmias resulting from coronary artery ligation in the anesthetized rat. Metoprolol was administered at different times after the onset of ischemia to determine any relationship between antiarrhythmic effects and the time of administration. Studies with two other thromboxane synthetase inhibitors, dazoxiben and carboxyheptylimizadole, and a thromboxane analogue, U 46,619, were performed on the early arrhythmias to investigate a possible role of thromboxane A2 in the genesis of ischemic arrhythmias. Pretreatment and very early intervention with metoprolol caused a significant reduction in the incidence of ventricular fibrillation (VF) in the 0-0.5 hr period. The number of ventricular ectopic beats (VEBs) and the incidence of ventricular tachycardia (VT) during the 0.5-4 hr period were markedly reduced by both pretreatment and late intervention with metoprolol. VEBs and VT in the 0-0.5 hr phase were reduced by UK 38,485 and carboxyheptylimidazole and increased by U 46,619. Administration of a combination of the drugs produced a significant reduction in early VF and late VEBs.