Beneficial effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on energy metabolism in ischemic dog hearts.
The effect of MET-88 [3-(2, 2, 2-trimethylhydrazinium) propionate], a gamma-butyrobetaine hydroxylase inhibitor, on the ischemic changes of energy metabolism was studied in the anesthetized dog. In the dog pretreated orally with MET-88 (50, 100 or 200 mg/kg/day) or placebo for 10 days, the left anterior descending coronary artery was occluded for 60 min, and the myocardium was taken from the left anterior descending coronary area (ischemic area) and left circumflex area (nonischemic area) for metabolic analysis. In the ischemic area, occlusion of the left anterior descending coronary artery decreased the tissue levels of adenosine triphosphate, adenosine diphosphate and creatine phosphate, increased the tissue levels of adenosine monophosphate and lactate, and decreased the value of the energy charge potential. These metabolic alterations, induced by occlusion of the left anterior descending coronary artery, were dose-dependently attenuated by MET-88. In the nonischemic area, MET-88 did not markedly change either the tissue levels of energy metabolites or the value of the energy charge potential. These results indicate that MET-88 attenuates the derangement of the energy metabolism in the ischemic myocardium, without affecting the energy metabolism in the nonischemic myocardium.
Kirimoto
T
T
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Nobori
K
K
Asaka
N
N
Muranaka
Y
Y
Tajima
K
K
Miyake
H
H
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002331:Carnitine / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism
D002317:Cardiovascular Agents; D008763:Methylhydrazines; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; C050147:3-(2,2,2-trimethylhydrazine)propionate; D000255:Adenosine Triphosphate; D002331:Carnitine; D003065:Coenzyme A