Investigations of the antifibrillatory activity of flunarizine and lidoflazine in isolated hearts of rabbits and guinea pigs

In Langendorff-perfused rabbit hearts, ventricular fibrillation threshold (VFT) was measured by applying rectangular impulses of 3ms duration at a frequency of 20Hz. Perfusion with 0.2 and 0.4 microM of flunarizine or 0.2 microM of lidoflazine produced a significant rise in VFT. When the hearts were perfused with higher concentrations of either drug (0.8 microM flunarizine, 0.4 and 0.8 microM lidoflazine), VFT did not continue to increase in a dose-dependent manner but rather a smaller increase in VFT than the previous dose was observed. Both drugs caused significant decrease in the spontaneous heart rate and amplitude of contraction of the isolated rabbit heart. In the Langendorff-perfused guinea pig heart, perfusion with 0.8 microM of flunarizine produced complete protection against ouabain-induced ventricular fibrillation while 7 out of 7 and 1 out of 6 hearts fibrillated in the presence of 0.2 and 0.4 microM of the drug respectively. During perfusion with 0.2, 0.4 and 0.8 microM of lidoflazine the incidence of ventricular fibrillation was 3 out of 6, and 5 out of 7 hearts respectively. These results may indicate a limited effectiveness of these 2 calcium entry blockers against ventricular fibrillation.