Abstract:
:The possible ischemia-selective Class III anti-arrhythmic action (selective action potential widening in ischemia) of the IKATP blocker glibenclamide was assessed in anesthetized rabbits during ischemia induced by complete occlusion of a coronary artery. Coronary artery occlusion caused an initial prolongation in monophasic action potential (MAP) duration at 90% repolarization from 145 +/- 2.8 ms (mean +/- S.E.M., n = 14) to 162 +/- 4.5 ms (P < 0.05) 1 min after ischemia. This was followed by a rapid and sustained shortening to 104 +/- 4.9 ms 5 min after the onset of ischemia (P < 0.05 from both values). Glibenclamide (3, 6, 12 or 24 mg/kg, i.v.) caused a statistically significant, dose-related reduction in the rate of MAP shortening induced by ischemia, whereas 0.3 mg/kg was without effect. The effective dose for a 50% maximal effect (ED50) was 13 +/- 0.8 mg/kg (n = 28). Despite this, there was no effect on the final magnitude of MAP shortening. Five min after induction of ischemia, there were no longer any detectable effects of glibenclamide on MAP duration. Glibenclamide significantly reduced the incidence of ventricular fibrillation, although the effect was not dose related. No differences were found in the latency to ventricular fibrillation between groups. Ventricular fibrillation occurred 10.6 +/- 1.1 min (n = 19) after the start of ischemia. In a similar experiment, 0.3 mg/kg glibenclamide i.v. did not affect the rate of MAP shortening, the final magnitude of MAP shortening or the occurrence of arrhythmias caused by ischemia. Since the action potential widening effects of glibenclamide in ischemic tissue were not observed at the time when arrhythmias occurred, it is unlikely that an ischemia-selective Class III anti-arrhythmic action contributes to the limited antiarrhythmic actions of glibenclamide.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Barrett TD,Walker MJdoi
10.1006/jmcc.1998.0664subject
Has Abstractpub_date
1998-05-01 00:00:00pages
999-1008issue
5eissn
0022-2828issn
1095-8584pii
S0022-2828(98)90664-2journal_volume
30pub_type
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