title: Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart.
abstract: We used low temperature to slow ion channel kinetics and studied the electrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial activation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were analyzed by epicardial activation sequence mapping. In the presence of quinidine, arrhythmias consistent with both triggered activity and reentry were observed. At baseline, triggered activity was not inducible, even though at 25 degrees C the recovery time was greater than that in the presence of quinidine at 36 degrees C. Also, with quinidine, the incidence of triggered activity decreased at 30 and 25 degrees C. Therefore prolongation of the recovery time per se does not cause triggered activity. Quinidine's use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperatures. These findings can be understood in terms of the known temperature sensitivities of the kinetics of the membrane ion channels responsible for activation and recovery. The results demonstrate that temperature can be used as a tool to elucidate mechanisms of drug action.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Spear
authors.forename: E N
authors.initials: EN
authors.lastname: Moore
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003080:Cold Temperature; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D011802:Quinidine / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D011802:Quinidine