The antiarrhythmic and antifibrillatory actions of bretylium and its o-iodobenzyl trimethylammonium analog, UM-360.
The antiarrhythmic, adrenergic-stimulating and blocking properties of bretylium and a structural analog UM-360, o-iodobenzyl trimethylammonium chloride, were studied in the anesthetized dog. Bretylium produced an initial sympathomimetic effect with a subsequent blockade of cardiac responses to sympathetic nerve stimulation. Bretylium was observed to produce an antifibrillatory effect when the vulnerability to fibrillation was measured as the current required to evoke ventricular fibrillation (ventricular fibrillation threshold) or the spontaneous development of ventricular fibrillation in response to a one-stage occlusion of the left anterior descending coronary artery for 20 minutes followed by release. In animals intoxicated with ouabain, however, bretylium was not effective in reversing the ventricular tachycardia. UM-360, in contrast to bretylium, did not produce adrenergic stimulation or blockade of sympathetic neuronal activity. UM-360, however, produced a marked antifibrillatory effect by increasing the electrical threshold to ventricular fibrillation and reducing the incidence of ventricular fibrillation in response to coronary artery occlusion. The results of this study suggest that the quaternary ammonium structure, as possessed by bretylium and UM-360, may be of significance with respect to the antiarrhythmic and antifibrillatory effects of these agents.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D001949:Bretylium Compounds / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007462:Iodobenzenes / Q000494:pharmacology*; D008297:Male; D010042:Ouabain; D013233:Stellate Ganglion / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology
D001949:Bretylium Compounds; D007462:Iodobenzenes; C025210:iodobenzyltrimethylammonium; D010042:Ouabain; D002122:Calcium Chloride