Effects of iloprost, a PGI2 derivative, on ischemic myocardial energy and carbohydrate metabolism in dogs.
Effects of iloprost, which is a stable prostacyclin analogue, on the ischemic myocardium were examined in the open-chest dog heart in terms of biochemical parameters. Ischemia was initiated by ligating the left anterior descending coronary artery. When the coronary artery was ligated for 3 min, the levels or glycogen, fructose-1,6-diphosphate (FDP), adenosine triphosphate and creatine phosphate decreased, and the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), lactate, adenosine diphosphate and adenosine monophosphate increased. During ischemia, therefore, energy charge potential was significantly decreased from 0.89 +/- 0.01 to 0.82 +/- 0.01, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were significantly increased from 1.75 +/- 0.30 to 29.05 +/- 5.70 and 13 +/- 3 to 393 +/- 112, respectively. Iloprost (0.1, 0.3, or 1 microgram.kg-1) was injected intravenously 5 min before the onset of ischemia. Iloprost (0.1, 0.3, and 1 micrograms.kg-1) reduced the ischemia-induced decrease in energy charge potential to 94, 74, and 86%, respectively, the increase in ([G6P] + [F6P])/[FDP] to 38, 29, 32%, respectively, and the increase in [lactate]/[pyruvate] to 67, 45, 65%, respectively. These results suggest that iloprost lessens the myocardial metabolic derangements produced by ischemia, and the most potent effect was obtained at the dose of 0.3 microgram.kg-1.
Ichihara
K
K
Department of Pharmacology, Asahikawa Medical College, Japan.
Yamamoto
K
K
Abiko
Y
Y
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005635:Fructosediphosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010725:Phosphocreatine / Q000378:metabolism
D005635:Fructosediphosphates; D005958:Glucosephosphates; D007773:Lactates; D010725:Phosphocreatine; D019298:Glucose-6-Phosphate; D000244:Adenosine Diphosphate; D006003:Glycogen; D016285:Iloprost; C029063:fructose-1,6-diphosphate