| Abstract: |
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. Consistent with the increase in ventricular effective refractive period and monophasic action potential duration in dogs, glibenclamide (10-7 - 10-5 mol/l) significantly increased action potential duration in normoxic canine Purkinje fibres to a maximum of 19 - 2% at 95% repolarization. These data suggest that the opening of ATP-dependent K+ channels contributes to action potential shortening duration ischaemia in rabbits, but do not provide evidence that glibenclamide, at the dose studied, reduces the susceptibility to electrically-induced ventricular fibrillation in dogs subjected to acute ischaemia. |
