Profile of coronary vasodilator and cardiac actions of bepridil revealed by use of isolated, blood-perfused heart preparations of the dog.

Abstract

We investigated the coronary vasodilator and cardiac actions of bepridil in various isolated, blood-perfused dog heart preparations. Intra-arterial bepridil increased blood flow in all preparations. In sinoatrial (SA) node preparations bepridil decreased sinus rate and produced atrial standstill in large doses. In paced atrioventricular (AV) node preparations, bepridil injected into the posterior septal artery (which supplies the AV node) increased AV conduction time (i.e., AV nodal conduction time) and in large doses produced second- or third-degree AV block. In the same preparations, bepridil in large doses injected into the anterior septal artery (which supplies the His-Purkinje ventricular system) prolonged AV conduction time (i.e., intraventricular conduction time). In paced papillary muscle preparations, bepridil reduced force of contraction only in large doses. In spontaneously beating papillary muscle preparations, bepridil decreased the rate of automaticity and the force of contraction as well. The order of effectiveness of bepridil on the above cardiovascular variables is as follows: coronary blood flow greater than AV nodal conduction greater than SA nodal automaticity much greater than ventricular automaticity ventricular muscle contraction much greater than intraventricular conduction. The results indicate bepridil to have a pharmacological profile different from that of verapamil, diltiazem, nifedipine, nicardipine, or KB-944.