Analyses of the cardiac action of the bradycardic agent, AQ-A 39, by use of isolated, blood-perfused dog-heart preparations.
The cardiac and coronary vasodilator actions of AQ-A 39 were investigated in various isolated, blood-perfused dog-heart preparations. AQ-A 39 was injected i.a. In sinoatrial (SA) node preparations, AQ-A 39 (3 micrograms-3 mg) decreased sinus rate but rarely produced atrial standstill even in large doses (1-3 mg). In paced atrioventricular (AV) node preparations, AQ-A 39 injected into the posterior septal artery (which supplies the AV node) increased AV conduction time (i.e., AV nodal conduction time) in rather large doses (100 micrograms-1 mg), but produced neither second-nor third-degree AV block even with the largest dose examined (1 mg). In the same preparations, AQ-A 39 injected into the anterior septal artery (which supplies the His-Purkinje-ventricular system) prolonged AV conduction time (i.e., intraventricular conduction time) in rather large doses (0.3-1 mg). In paced papillary muscle preparations, AQ-A 39 reduced force of contraction only in large doses (1-3 mg). In spontaneously beating papillary muscle preparations, AQ-A 39 (10 micrograms-3 mg) decreased rate of automaticity and force of contraction only with large doses (1-3 mg). In all preparations, AQ-A 39 (30 micrograms-3 mg) increased blood flow. The order of effectiveness of AQ-A 39 on the above cardiovascular variables is as follows: ventricular automaticity not equal to SA nodal automaticity much greater than AV nodal conduction not equal to intraventricular conduction not equal to coronary blood flow not equal to ventricular muscle contraction.(ABSTRACT TRUNCATED AT 250 WORDS)