Modification by glibenclamide of the electrophysiological consequences of myocardial ischaemia in dogs and rabbits.
Glibenclamide has been shown to block ATP-dependent K+ channels in the heart and prevent the shortening of cardiac action potentials caused by hypoxia in vitro. The present study examines the ability of glibenclamide to modify the effect of acute ischaemia on monophasic action potential duration in pentobarbital-anaesthetized rabbits, and on monophasic action potential duration and ventricular fibrillation threshold in pentobarbital-anaesthetized dogs. Left ventricular endocardial monophasic action potential duration was measured using a contact electrode catheter, and ventricular fibrillation threshold was measured by the single pulse method. Ischaemia was produced in rabbits by occluding the circumflex coronary for 5 min and in dogs by occluding the left anterior descending coronary artery for 40 min. In rabbits, glibenclamide (0.3-3 mg/kg, i.v.) had no effect on baseline monophasic action potential duration, but attenuated action potential shortening during ischaemia in a dose-related manner. In dogs, monophasic action potential duration did not shorten during ischaemia in the vehicle group, but tended to increase in the glibenclamide group (0.5 mg/kg, i.v.) both before and during ischaemia (7 +/- 5% and 14 +/- 8%, respectively, NS). Likewise, ventricular effective refractory period was significantly increased by glibenclamide prior to ischaemia (5 +/- 1%). Ventricular fibrillation threshold tended to increase during 40 min of ischaemia in vehicle-treated dogs (40 +/- 29%, NS), but was unchanged during ischaemia in the glibenclamide-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Smallwood
J K
JK
Department of Cardiovascular Pharmacology, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285.
Ertel
P J
PJ
Steinberg
M I
MI
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000503:physiopathology
D005905:Glyburide