Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

Abstract

The cardiac and coronary effects of AN-132, a new antiarrhythmic agent, were investigated in isolated, blood-perfused atrioventricular (AV) node, sinoatrial (SA) node and papillary muscle preparations of dogs. AN-132 was administered intraarterially. In AV node preparations, whether injected into the anterior septal artery (ASA; supplying the His-Purkinje-ventricular system) or the posterior septal artery (PSA; supplying the AV node), AN-132 prolonged AV conduction time and produced second- or third-degree AV block at large doses in some preparations. Moreover, only when injected into the ASA AN-132 produced a broadening and diminution of amplitude of bipolar electrograms obtained from the right bundle branch and the ventricular septum. In SA node preparations, AN-132 decreased sinus rate and produced atrial standstill at large doses in some preparations. In paced papillary muscle preparations, AN-132 reduced the force of contraction. In spontaneously beating papillary muscle preparations, AN-132 decreased the rate of automaticity and the force of contraction. In all preparations, AN-132 produced a transient increase in blood flow only at large doses. The order of potencies of AN-132 based on the doses that produced 15% suppressions of the above cardiovascular variables was as follows: cardiac muscle contraction greater than ventricular automaticity greater than or equal to intraventricular conduction greater than AV nodal conduction greater than or equal to coronary blood flow greater than SA nodal automaticity.