title: Glibenclamide attenuates ischemia-induced acidosis and loss of cardiac function in rats.
abstract: Previous research has shown that the sulfonylurea derivative glibenclamide may improve post-ischemic cardiac functional recovery. Although K(ATP) channel blockade is a possible explanation for this observation, alternative mechanisms exist. Therefore, we simultaneously recorded cardiac function and the intracellular concentration of ATP, phosphocreatine, Pi and pH before and after ischemia in the presence of glibenclamide or vehicle. (31)Phosphorus magnetic resonance (MS) spectroscopy on erythrocyte-perfused, isolated working rat hearts was performed. Glibenclamide 4 micromol l(-1) or vehicle alone was tested (both n=5). The following protocol was used: 8 min performance assessment, 10 min drug treatment, 12 min global ischemia, 20 min reperfusion with drug treatment and 8 min functional recovery assessment. Compared with vehicle, glibenclamide significantly decreased coronary blood flow (59.5+/-7.0% vs. 94.3+/-1.3%, P=0.008), ischemia-induced cardiac functional loss (7.4+/-1.3% vs. 18.8+/-3.3%; P=0.019) as well as the ischemia-induced intracellular acidosis (6.75+/-0.01 vs. 6.43+/-0.03 for vehicle, P=0.03). In conclusion, glibenclamide is able to reduce the myocardial functional loss after ischemia while preserving pH but not ATP levels during ischemia. This suggests that the beneficial response to glibenclamide is probably not the result of myocardial K(ATP) channel blockade, but may be explained by inhibition of glycolysis.
authors.affiliation: Department of Physiology 237, University Medical Center Nijmegen, P.O. Box 9101, NL-6500 HB, Nijmegen, The Netherlands.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Legtenberg
authors.forename: Ralph J F
authors.initials: RJ
authors.lastname: Houston
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.forename: Berend
authors.initials: B
authors.lastname: Oeseburg
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000138:Acidosis / Q000188:drug therapy*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide