Enhancement of ischemic myocardial metabolic derangement by glibenclamide.
We examined whether opening of the ATP-sensitive potassium (KATP) channels in the ischemic myocardium plays an important cardioprotective role during ischemia. Dogs were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). Sixty minutes after treatment of the dog with glibenclamide (0.3 or 3 mg/kg, i.v.), the LAD was ligated. At 3 or 15 min after LAD ligation, left ventricular tissue was taken from the ischemic region to measure tissue metabolite levels. After ischemia, the tissue levels of ATP and creatine phosphate decreased to 49-74% and 26-34%, respectively, and lactate level increased to 380-660%. Ischemia (either 3 or 15 min) increased the levels of G6P and F6P and decreased the FDP level, indicating the inhibition of glycolysis. Glibenclamide at either dose decreased the level of blood glucose by 20-30% and increased the blood insulin level twice. The decrease in ATP and increase in lactate due to ischemia were significantly enhanced by glibenclamide at a dose of 3 mg/kg. The increase in G6P due to 15 min of ischemia were also enhanced significantly by 0.3 and 3 mg/kg of glibenclamide. Glibenclamide worsened the metabolic alterations produced by ischemia. These results suggest that KATP channels that can be inhibited by glibenclamide may perform some functions in the ischemic myocardium.
Department of Pharmacology, Asahikawa Medical College, Japan.
M
M
Kamigaki
K
K
Ichihara
Y
Y
Abiko
D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects
D001786:Blood Glucose; D005636:Fructosephosphates; D005958:Glucosephosphates; D007328:Insulin; D015221:Potassium Channels; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D005905:Glyburide