Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs.
The present study was undertaken to examine whether dichloroacetate, which inhibits pyruvate dehydrogenase kinase and, therefore, increases the activity of pyruvate dehydrogenase, attenuates myocardial acidosis and metabolic changes induced by coronary occlusion. In dogs anesthetized with pentobarbital, the left anterior descending coronary artery was incompletely occluded to reduce the left anterior descending flow to a half to one third of the original flow (partial occlusion) to produce myocardial (regional) ischemia. Partial occlusion was continued for 90 min, and a bolus injection of saline or dichloroacetate was made intravenously 30 min after the onset of occlusion. Partial occlusion decreased myocardial pH significantly. An injection of dichloroacetate (150 mg/kg) increased myocardial pH that had been lowered by partial occlusion. Myocardial metabolites were measured in other dogs. Partial occlusion decreased the myocardial levels of adenosine triphosphate, creatine phosphate and energy charge potential, and increased that of lactate significantly, without affecting the myocardial levels of pyruvate and nonesterified fatty acids. Dichloroacetate attenuated the ischemia-induced changes in the myocardial levels of adenosine triphosphate, creatine phosphate, energy charge potential and lactate. These results indicate that dichloroacetate attenuates the myocardial acidosis and metabolic changes during coronary partial occlusion.
Sakai
K
K
Department of Pharmacology, Asahikawa Medical College, Japan.
Ichihara
K
K
Nasa
Y
Y
Kamigaki
M
M
Abiko
Y
Y
D000138:Acidosis / Q000188:drug therapy* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid
D005230:Fatty Acids, Nonesterified; D007773:Lactates; D011773:Pyruvates; D010725:Phosphocreatine; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid