Pro- and antiarrhythmic effects of d-sotalol and dl-sotalol in an isolated tissue model of ischemia and reperfusion.
Pro- and antiarrhythmic effects of dl-sotalol and d-sotalol were compared with their electrophysiological actions in an isolated tissue model of simulated ischemia and reperfusion. Microelectrode recordings were made from endo- and epicardium of isolated guinea pig right ventricular free walls. An electrocardiogram also was recorded by two electrodes at opposite ends of the tissue bath. Regular stimulation was delivered to the endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in 33% of hearts in ischemia and 73% of hearts in early reperfusion. Arrhythmias were accompanied by prolongation of transmural conduction time (CT) and abbreviation of endocardial action potential duration (APD) and effective refractory period. Both dl-sotalol and d-sotalol (100 microM) significantly (P < .05) prolonged endocardial APD, effective refractory period and epicardial APD under preischemic conditions; however, these effects were lost during simulated ischemia and early reperfusion. dl-Sotalol abolished arrhythmias in ischemia and reduced the incidence of reperfusion arrhythmias to 30%. This agent attenuated prolongation of transmural CT by ischemia and decreased the incidence of conduction block. In contrast, d-sotalol (100 microM) increased arrhythmias in ischemia to 80% and did not change the incidence of reperfusion arrhythmias (60%). The proarrhythmic effects of d-sotalol were accompanied by prolongation of transmural CT, increased incidence of conduction block and decreased epicardial excitability. Thus, in this model of global ischemia and reperfusion, antiarrhythmic effects were observed with dl-sotalol but not with the predominantly type III isomer, d-sotalol.
Pasnani
J S
JS
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
G R
GR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control*; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D013015:Sotalol