Effects of allopurinol on reperfusion arrhythmias in isolated ventricles.
Electrophysiological effects of allopurinol on arrhythmias were studied in isolated segments of guinea pig right ventricular free walls paced from endocardium. A high-gain electrocardiogram as well as transmembrane electrical activity from endo- and epicardium were recorded. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode solution. Sustained or nonsustained ventricular tachycardia, bigeminy, and trigeminy with characteristics of transmural reentry occurred in early reperfusion in 75% of 20 control preparations. Arrhythmias were associated with prolongation of transmural conduction time and abbreviation of endocardial effective refractory period (ERP). Allopurinol strongly reduced the incidence of reperfusion arrhythmias (20-33%) between 10 and 100 microM, whereas either lower or higher concentrations (5 or 500 microM) were less effective (43 and 50%). Antiarrhythmic efficacy correlated with significant attenuation of reperfusion-induced transmural conduction delay (P less than 0.05 or 0.01). Allopurinol did not affect endocardial conduction times nor did it significantly alter endocardial action potential duration or ERP. Our results indicate that allopurinol exerts antiarrhythmic efficacy during reperfusion by selectively attenuating defects related to anisotropic tissue properties.
Li
G R
GR
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
G R
GR
D000200:Action Potentials; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D003327:Coronary Disease / Q000503:physiopathology; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010496:Pericardium / Q000503:physiopathology; D011930:Reaction Time; D012032:Refractory Period, Electrophysiological; D015424:Reperfusion
D000493:Allopurinol