Comparative effects of fast- and slow-ion channel blocking agents on reperfusion-induced arrhythmias in the isolated perfused rat heart.

The effects of bepridil (1-4 microM), a new antianginal agent which reduces the intensity of both the fast and slow inward ionic currents in myocardium, on reperfusion-induced arrhythmias (RA) in the isolated perfused rat heart were compared with those of tetrodotoxin (0.16-1.57 microM), verapamil (0.5-2 microM), diltiazem (1-2 microM), nifedipine (0.02-0.2 microM), and nitrendipine (0.02-0.2 microM). In comparable negative inotropic concentrations, neither nifedipine nor nitrendipine reduced the incidence of RA, whereas the other four agents did. Protection against RA does not appear to be related to coronary vasodilatation or to a reduction in the degree of ischaemia as assessed by lactate dehydrogenase release. However, negative chronotropism appears to be relevant in the mechanism of action of the calcium antagonists. Substantial protection against RA by all active drugs was associated with PR prolongation and/or atrioventricular block or suppression of sinus rhythm. It is concluded that bradycardia may play an important role in the antiarrhythmic action of bepridil, but the relative contributions made by inhibition of the inward calcium and/or sodium currents remain unclear.