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

Abstract

Profile of AN-132, a New Diamine Derivative Antiarrhythmic Agent, Revealed in the Isolated, BloodPerfused Dog Heart. Tohoku J. exp. Med., 1988, 156 (1), 65-78 -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 cardiovas cular variables was as follows : cardiac muscle contraction>ventricular automaticity?intraventricular conduction>AV nodal conduction coronary blood flow> SA nodal automaticity. -AN-132 ; antiarrhythmic agent ; AV nodal conduction ; intraventricular conduction ; negative inotropy AN-132 (Fig. 1), a newly synthesized antiarrhythmic agent, has been reported to be effective in several animal models of cardiac arrhythmias, whether given

Utilization of an Isolated, Blood-Perfused Canine Papillary Muscle Preparation as a Model to Assess Efficacy and Adversity of Class I Antiarrhythmic Drugs

“…Class I antiarrhythmic drugs and TTX used in this study decreased VR in a dose dependent manner, whereas verapamil virtually did not affect it in doses that suppressed the DT and increased the CBF. Similar results were reported previously (2,5,7,(34)(35)(36)(37)(38). The ventricular automaticity observed in un paced papillary muscle preparations has been thought to originate in Purkinje fibers in the ventricular septum (2).…”

“…Effects on coronary blood flow: The class I antiar rhythmic drugs increase CBF (3,5,6,12,31), and these effects can be easily assessed in this model. To analyze fur ther the effects of class I drugs on CBF, we compared their effects with TTX and verapamil.…”

“…As the papillary muscle preparation had an automa ticity originating in the Purkinje fiber of the ventricular septum (2), it showed a spontaneous regular contraction when the electrical stimulation was stopped (4,5,7). Using this spontaneously beating papillary muscle prepa ration, VR was measured with a cardiotachograph (1321, NEC San-ei Instruments) triggered by bipolar electro grams of the papillary muscle.…”

“…Based upon this need, we utilized an isolated, blood perfused canine papillary muscle preparation to precisely study the direct cardiac effects of the class I antiar rhythmic drugs under physiologically stable conditions (2)(3)(4)(5)(6)(7)(8). An electrically paced preparation was used to measure intraventricular conduction time (IVCT), coro nary blood flow (CBF) and developed tension of the papil lary muscle (DT), while a spontaneously beating prepa ration was used to measure ventricular automaticity rate (VR).…”

Cardiovascular Effects of AN‐132, a New Diamine Analogue of Lidocaine

“…Various cardiovascular effects of AN-132 were examined in isolated, blood-perfused dog heart (9). In the atrioventricular (AV) node blood-perfused preparations, AN-132 dose-dependently prolonged the AV conduction time and finally caused second-and third-degree AV block.…”