The effects of the novel anti-anginal compound RS 43285 on myocardial conduction in the anaesthetized dog

Abstract

1. A pentobarbitone-anaesthetized canine model of myocardial conduction was developed to evaluate drug effects on intra-atrial (I-A), intra-ventricular (I-V) and atrioventricular (A-V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the sino-atrial (SA) node to re-establish sinus rhythm on switching off electrical pacing were also considered. The effects of the novel anti-anginal compound RS 43285-193 ((+/-)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy-3-(2-methoxyphenoxy)propyl] -1-piperazine acetamide dihydrochloride) were compared to those of the standard anti-anginal compounds nicardipine, nifedipine and verapamil. 2. In the dose range 15-7000 micrograms kg-1, RS 43285 had no significant effects on I-A, I-V or A-V conduction either at rest or during electrical pacing and did not affect the re-establishment of sinus rhythm. 3. Nicardipine had no effects on conduction parameters at resting heart rate. There were no effects on I-A or I-V conduction on electrical pacing but A-V conduction was increased at 200-500 micrograms kg-1 (with a 2:1 A-V conduction block in two out of six dogs); this was accompanied by a prolongation of the interval to reversion of sinus rhythm. 4. Nifedipine had no significant effects on I-A or I-V conduction but significantly prolonged A-V conduction at 1000 micrograms kg-1 and this dose also increased the interval to SA node recovery. 5. Verapamil did not effect I-A or I-V conduction. However, A-V conduction was affected with a significant prolongation occurring at resting heart rate at 100-400 Atg kg-' and a 2:1 A-V block in one dog at rest. During right atrial pacing verapamil significantly increased A-V conduction at 50- 400 fig kg-'. All dogs exhibited a 2:1 A-V conduction block at the highest frequency at 400 jig kg-'.