Electrophysiologic effects of a new antiarrhythmic agent, recainam, on isolated canine and rabbit myocardial fibers.
Recainam (Wy 42,362) is a new antiarrhythmic agent undergoing clinical evaluation, but its electrophysiologic effects in cardiac muscle are poorly defined. With microelectrode techniques, its profile in isolated preparations of dog and rabbit hearts was determined using drug concentrations of 10 to 300 microM. Recainam induced a concentration- and frequency-dependent decrease in the maximal rate of rise of the phase 0 of the action potential (Vmax), action potential amplitude and overshoot potential, with little or no change in the effective refractory period except in Purkinje fibers, in which it was markedly reduced. At a 300 microM concentration, Vmax was reduced 51% (p less than 0.001) in ventricular muscle and 44% (p less than 0.001) in atrial muscle, with no change in action potential duration or effective refractory period. At the same drug concentration in Purkinje fibers, Vmax was decreased by 41% (p less than 0.01), action potential duration at 90% repolarization by 36% (p less than 0.01) and effective refractory period by 34% (p less than 0.01). Recainam had no significant effect on the sinoatrial node, but it depressed phase 4 depolarization in isoproterenol-induced automaticity in Purkinje fibers. The drug had no effect on slow channel potentials induced by high concentrations of potassium and isoproterenol. The data indicate that the electrophysiologic profile of recainam in isolated cardiac muscle is consistent with the overall effects of class IC agents without having an effect on the slow calcium channel. Its major action is to depress Vmax, with little effect on refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)
Takikawa
R
R
Department of Cardiology, Wadsworth Veterans Administration Hospital, Los Angeles, California 90073.
Kamiya
K
K
Kato
R
R
Singh
B N
BN
D000200:Action Potentials; D000818:Animals; D016275:Atrial Function; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000502:physiology*; D016276:Ventricular Function
D010671:Phenylurea Compounds; C039524:recainam