Differential effects of organic slow inward current inhibitors, verapamil and nifedipine, on rate of atrioventricular rhythm and supraventricular tachycardia in the canine isolated, blood-perfused AV node preparation

The present experiments were performed to elucidate whether the organic slow inward current inhibitors, verapamil and nifedipine, would affect the automaticity of the atrioventricular (AV) junctional area. 1. In the canine isolated, blood-perfused AV node preparation, there appeared AV rhythm at a rate of 54±3 beats/min (n=12) after elimination of the sinoatrial node activity. The AV rhythm originated from the distal portion of the AV junctional area supplied by the anterior septal artery (ASA) and was attended by retrograde conduction with ventriculo-atrial (VA) conduction time of 94±6 ms (n=12). 2. During AV rhythm, verapamil and nifedipine in a dose range of 1–10 nmol injected into the ASA affected neither rate of AV rhythm nor VA conduction time. 3. When injected into the posterior septal artery (PSA) which supplies the proximal portion of the AV junctional area, the two substances in a similar dose range to that given into the ASA produced dose-related prolongation of VA conduction time and VA conduction block at 10 nmol. However, the rate of AV rhythm remained unchanged in all the dose range of the two drugs examined. 4. Verapamil and nifedipine (10 nmol) given into the ASA failed to modify the increase in rate of AV rhythm induced by noradrenaline (NA) injected into the same artery. 5. When NA in a dose range of 100 pmol to 3 nmol was injected into the PSA, AV rhythm was transiently replaced by supraventricular tachycardia, a rapid increase in a rate of the automaticity of the PSA area which is usually extremely low and masked by AV rhythm. Under this circumstance VA conduction time was first shortened and then VA conduction was replaced by antegrade conduction. 6. Verapamil and nifedipine (10 nmol) given into the PSA, which caused retrograde VA conduction block, reduced the rate of NA-induced supraventricular tachycardia. 7. These results indicate that two pacemakers within the AV junctional area have different pacemaking mechanisms; NA-induced automaticity of the proximal portion depends on the slow inward Ca/Na current whereas the inherent automaticity and that enhanced by NA of the distal portion do not.