title: Effect of glibenclamide on ischemic canine myocardium with glucose infusion.
abstract: Glibenclamide, an ATP-sensitive K (K ATP) channel blocker, worsens the ischemia-induced metabolic derangement in the heart through inhibition of K ATP channels. We examined whether the hypoglycemic effect of glibenclamide was involved in the worsening of myocardial energy metabolism during ischemia. Pentobarbital-anesthetized dogs were subjected to 15-min ligation of the left anterior descending coronary artery. Either vehicle (dimethyl sulfoxide, DMSO) or glibenclamide (1 mg/kg) was injected i.v. 10 min before the ligation. In half of the animals given glibenclamide, glucose was continuously infused at 3 mg/kg per min immediately after glibenclamide injection. Glibenclamide increased the serum insulin level and decreased the blood glucose level. Glucose infusion completely abolished the hypoglycemia due to glibenclamide. Glibenclamide enhanced the decrease in ATP and total adenine nucleotides and increase in tissue lactate caused by ischemia. Glucose infusion did not cancel the augmentation of ischemia-induced alterations of myocardial energy metabolism caused by glibenclamide. These results suggest that K ATP channels directly play an important role in endogenous mechanisms of myocardial protection against ischemic damage.
authors: Third Department of Internal Medicine, Asahikawa Medical College, 4-5 Nishikagura, Asahikawa 078, Japan.
authors: M
authors: M
authors: Kamigaki
authors: K
authors: K
authors: Ichihara
authors: Y
authors: Y
authors: Kohgo
authors: Y
authors: Y
authors: Abiko
mesh_terms: D000818:Animals; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D005947:Glucose; D005905:Glyburide