Acute effects of cocaine on catecholamines and cardiac electrophysiology in the conscious dog

To evaluate the electrophysiologic and neurohumoral effects of cocaine on the sinus node, atrium, atrioventricular node, and His-Purkinje system, 14 conscious dogs were studied before and after an infusion titrated to maximum tolerance or to increase the systolic blood pressure by at least 15%. Plasma cocaine and catecholamine levels, blood pressure, surface and intracardiac electrograms were recorded. Programmed electrical stimulation was performed from the right atrium. The sinoatrial conduction time, paced PR interval, atrioventricular nodal conduction time, atrioventricular nodal effective refractory period and blood pressure increased. Plasma noradrenaline, adrenaline and dopamine increased and remained at two to three times control levels throughout the study although plasma cocaine levels declined. Adrenaline levels were strongly correlated with the hemodynamic response while plasma cocaine levels were not. No sustained spontaneous atrial or ventricular arrhythmias were recorded after cocaine infusion. Atrial fibrillation with a slow ventricular response was induced by pacing after cocaine in only three dogs. There were no significant changes in pacing threshold, right intra-atrial conduction time, infranodal conduction time, heart rate, QRS or QT. No pacing induced infranodal block occurred. The cocaine dose rate infused was 2.8 ± 1.2 mg/kg; cocaine plasma levels were 1402 ± 885 ng/mL immediately after the initial infusion and 525 ± 321 ng/mL at the end of the study. It is concluded that in normal canine heart cocaine increases blood pressure, sinoatrial conduction time, atrioventricular nodal effective refractory period, paced PR interval, atrioventricular nodal conduction time, plasma catecholamines and susceptibility to atrial fibrillation. These findings cannot be explained solely by increased sympathetic nervous system activity and suggest participation of the parasympathetic nervous system.