Selectivity of alinidine, a bradycardic agent, for SA nodal automaticity versus other cardiac activities in isolated, blood-perfused dog-heart preparations.
Selectivity of alinidine for SA nodal automaticity vs. other cardiac activities was investigated using isolated, blood-perfused SA node, AV node and papillary muscle preparations of the dog. The drug was administered intra-arterially. In SA node preparations alinidine (1 microgram-1 mg) produced a dose-dependent decrease of sinus rate down to about 74% of the basal value at 1 mg, but no atrial standstill. In AV node preparations alinidine, injected into the posterior septal artery (PSA) which supplies the AV node, prolonged AV conduction time up to about 124% of the basal value but only in large doses (30 micrograms-1 mg). In the same preparations, when injected into the anterior septal artery, which supplies structures from the His bundle down to the ventricular septum (the intraventricular conduction system), alinidine in large doses (300 micrograms-1 mg) also prolonged AV conduction time nearly to the same extent as when injected into the PSA. In both cases neither second- nor third-degree AV block occurred. In paced papillary muscle preparations alinidine reduced the force of contraction down to about 64% of the basal value but in large doses (100 micrograms-1 mg). In spontaneously beating papillary muscle preparations alinidine reduced the rate of ventricular automaticity down to about 78% of the basal value but in large doses (100 micrograms-1 mg). Alinidine (100 micrograms-1 mg) produced a transient increase in blood flow in these preparations but not in SA node preparations. The cardiac effects of alinidine were longer-lasting than its vascular effect and the reduction of sinus rate was particularly long-lasting. The order of selectivity of alinidine determined from the above results is as follows: SA nodal automaticity much greater than ventricular automaticity greater than intraventricular conduction divided by AV nodal conduction divided by cardiac muscle contraction divided by coronary blood flow. Such a cardiovascular profile of alinidine is different from that of AQ-A 39, another bradycardic agent, which is nearly equi-effective on both SA nodal and ventricular automaticity.