Abstract

Quindonium is a bradycardic agent which disrupts regular sinus rhythm in barbiturateanesthetized dogs. Sinus bradycardias were interrupted by periods of sinus acceleration during which the disturbances in the lead II electrocardiogram were either minor or absent. The rate and rhythm changes were resistant to vagotomy or atropine, propranolol and pentolinium. Propranolol enhanced the responses and precipitated arrhytimias in resistant animals; carotid sinus denervation had the opposite effect. The sequence of atrial activation was not altered by quindonium and there were only slight prolongations in intra-atrial and atrioventricular conduction times at spontaneous rates. Fixed-rate pacing revealed a significant prolongation in atrioventricular conduction time; however, formaldehyde (and propranolol)-induced atrioventricular heart block did not interfere with the atrial rate and rhythm response patterns. Destruction of the sinoatrial node prevented the arrhythmic, but not the bradycardic effects of quindonium. Injections into the sinus node artery evoked responses qualitatively similar to those seen after i.v. administration. Quindonium similarly altered pacemaker function in the in vitro guinea-pig atria and dog isolated heart preparations. At arrhythmic doses, there was no interference in the responses to cardio-accelerans nerve stimulation and a prolongation of isoproterenol-induced tachycardias. The results indicate that quindonium has a direct action on the sinoatrial node and/or the surrounding atrial myocardium. The emergence of latent atrial pacemakers or the periodic escape of the depressed sinoatrial node pacemaker could account for the periods of cardio-acceleration associated with the quindonium bradycardias.