Effects of diltiazem on reperfusion-induced arrhythmias in vitro and in vivo

The effects of the calcium antagonist, diltiazem, on myocardial injury during ischemia and reperfusion were studied both in vitro, in the isolated rat heart, and in vivo, in a closed-chest pig model. In the isolated rat heart, administration of diltiazem before or at the onset of ischemia resulted in a dose-dependent reduction of the incidence and duration of ventricular fibrillation. This reduction was associated with a dose-dependent reduction in overflow of ATP catabolites (adenosine, inosine, hypoxanthine and xanthine). Both changes were significant at concentrations of 3×10−7 m diltiazem and higher. When 3×10−7 m diltiazem was administered upon reperfusion no effect on the incidence of ventricular fibrillation and on ischemia induced total purine overflow was observed. However, the duration of ventricular fibrillation and purine overflow at 5 min after reperfusion were significantly reduce