Effects of quinidine on arrhythmias and conduction in an isolated tissue model of ischemia and reperfusion.
Transmembrane electrical activity from endo- and epicardium and a high-gain ECG were recorded from isolated segments of guinea pig right ventricles. Endocardium was stimulated. Tissues were exposed to ischemic conditions for 15 min and then reperfused with "normal" Tyrode's solution. Ventricular tachycardia, bigeminy, or trigeminy with characteristics of transmural reentry occurred in early reperfusion in 68% of control hearts. Arrhythmias were associated with prolongation of the transmural conduction time (CT) and abbreviation of the endocardial effective refractory period (EP). Quinidine significantly suppressed reperfusion arrhythmias at 1 and 5 microM, slightly increased the incidence of arrhythmias at 10 microM, and again suppressed arrhythmias at 50 and 100 microM. At 1 and 5 microM, quinidine prevented or attenuated prolongation of the transmural CT by ischemic conditions and reperfusion. The transmural CT was not significantly changed at 10 microM, and was further prolonged at 50 and 100 microM quinidine. The endocardial ERP was prolonged by 50 and 100 microM quinidine during ischemic conditions and reperfusion. In epicardial slices, 5 microM quinidine shortened the CT transverse to the fiber orientation during reperfusion but had no effect on the longitudinal CT. Thus, antiarrhythmic efficacy of low concentrations of quinidine may occur through differential effects dependent on tissue anisotropy.
Li
G R
GR
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
G R
GR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology*; D004594:Electrophysiology; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011802:Quinidine / Q000494:pharmacology*; D016278:Ventricular Function, Right / Q000187:drug effects
D011802:Quinidine