Metoprolol reduces reperfusion-induced fibrillation in the isolated rat heart: protection is secondary to bradycardia.

We studied the effect of metoprolol on the incidence of reperfusion-induced ventricular fibrillation in the isolated rat heart with transient coronary artery occlusion and reperfusion. When administered prior to ischemia, metoprolol produced a dose-dependent reduction in reperfusion-induced ventricular fibrillation. Thus, with 1, 10, 30, 50, 100, and 200 mumol/L metoprolol, total ventricular fibrillation (reversible plus irreversible) was reduced from its control incidence of 100% to 91%, 83%, 58% (p less than 0.05), 25% (p less than 0.001), 25% (p less than 0.001), and 0% (p less than 0.001), respectively. Heart rate was also reduced in a dose-dependent manner from its control value of 268 +/- 6 beats/min to less than 75% at the highest concentration of metoprolol. Coronary flow was unaffected by metoprolol. Doses of metoprolol (1 and 10 mumol/L) that had no significant effect on heart rate had no antiarrhythmic effect. In additional experiments with a higher dose of metoprolol (50 mumol/L), hearts were paced to the rate of the drug-free control group and the antiarrhythmic effect of metoprolol was lost. When drug-free control hearts had their heart rate reduced to that of the metoprolol-treated hearts, a similar antiarrhythmic effect was observed. When metoprolol was administered just prior to reperfusion, no antiarrhythmic effects were observed. In further studies, we investigated the effect of the early administration of metoprolol (50 mumol/L) on the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of preceding ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)