Effect of perhexiline on atrioventricular nodal function of anesthetized dogs

We investigated the effects of perhexiline, a calcium-antagonistic vasodilator, on atrioventricular (AV) conduction in anesthetized open-chest dogs and in isolated, blood-perfused AV node preparations of the dog. Perhexiline, 3 mg/kg, prolonged the AV conduction time from 103.0 +/- 4.4 to 115.3 +/- 4.0 msec (p less than 0.05) in dogs with intact cardiac nerves. In dogs on which vagotomy and stellectomy had been performed, basal AV conduction time was 119.0 +/- 5.0 msec; 3 mg/kg of perhexiline barely prolonged it (121.0 +/- 7.0 msec). Thus, the negative dromotropic effect of perhexiline was abolished by denervation. The functional refractory period of the AV node was also lengthened with 3 mg/kg of perhexiline in the nerve-intact dogs (from 246.0 +/- 15.7) to 270.0 +/- 15.5 msec), but was scarcely affected by perhexiline in the cardiac denervated dogs (from 296.7 +/- 15.7 to 303.2 +/- 13.6 msec). Verapamil, 0.1-0.3 mg/kg, exerted a negative dromotropic effect in both innervated and denervated hearts. A direct inhibitory effect of perhexiline on AV conduction was observed in isolated blood-perfused AV node preparations, but it was much weaker when compared with that of verapamil.