Differential effects of glyburide on premature beats and ventricular tachycardia in an isolated tissue model of ischemia and reperfusion.
Possible anti- and proarrhythmic effects of glyburide, an ATP-sensitive K+ channel blocker, were assessed in an isolated tissue model of reperfusion. Transmembrane electrical activity was recorded from endo- and epicardium of isolated segments of guinea pig right ventricular free walls, or two sites on papillary muscles with microelectrodes. An electrocardiogram was recorded by two electrodes placed at opposite ends of the tissue bath. Regular stimulation was delivered to endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Rapid sustained or nonsustained ventricular tachycardia, bigeminy or trigeminy with characteristics of transmural re-entry occurred early in reperfusion in 50% of free walls. Triggered arrhythmias with characteristics of oscillatory afterpotentials (delayed afterdepolarizations) occurred in 20%. Arrhythmias were accompanied by prolongation of transmural conduction times and abbreviation of endocardial effective refractory periods and action potential durations. Glyburide (3 or 30 microM) significantly attenuated abbreviation of action potential durations and effective refractory periods during ischemic conditions and early reperfusion. Neither endocardial nor transmural conduction times were modified by glyburide; however, glyburide significantly decreased the incidence of transmural conduction block during ischemic conditions. Glyburide abolished reperfusion arrhythmias with characteristics of re-entry, but potentiated oscillatory afterpotentials in papillary muscles and triggered arrhythmias with characteristics of oscillatory afterpotentials in free walls. Identical effects were seen with glyburide present in ischemic solution, or in both ischemic and reperfusion solutions, but no effect was observed with glyburide present only in reperfusion. Our study demonstrates possible cellular mechanisms underlying simultaneous pro- and antiarrhythmic drug effects exerted on late premature beats and rapid arrhythmias and closely coupled premature beats.
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; D005117:Cardiac Complexes, Premature / Q000209:etiology*; D004558:Electric Stimulation; D004562:Electrocardiography; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury; D013610:Tachycardia / Q000209:etiology*
D005905:Glyburide