title: [Effects of dichloroacetate in the ischemic heart. Analysis of hemodynamics, myocardial energy metabolism and myocardial pH].
abstract: The effects of dichloroacetate (DCA), which is known to have a beneficial effect on lactic acidosis, were examined on myocardial acidosis during coronary occlusion in dogs. Ischemia was induced by complete ligation of the left anterior descending coronary artery (LAD) of the open-chest dog heart. DCA 100 mg/kg or 200 mg/kg was administered intravenously 10 or 60 min prior to the occlusion of LAD. DCA did not change the LAD flow, decreased heart rate, increased both systolic and diastolic blood pressures transiently. LAD occlusion significantly increased the ST segment of the epicardial ECG in the saline-treated group. DCA administered prior to the LAD occlusion caused 50% decrease of the elevation in ST segment during ischemia. Ischemia accelerated anaerobic metabolism in the myocardium; the levels of glycogen, adenosine triphosphate (ATP) and creatine phosphate (CP) decreased, and lactate increased during ischemia. Calculated energy charge potential was decreased, and [( G6P] + [F6P])/[FDP] ratio was increased by ischemia. The decreased levels of glycogen, ATP, CP in DCA-treated group were similar to those in saline-treated group during 3 min ischemia. Pretreatment of DCA reduced the accumulation of myocardial lactate by ischemia. There were no differences in variables except myocardial lactate levels between DCA 100 mg/kg and 200 mg/kg. The myocardial lactate levels were lower in both nonischemic and ischemic dogs by DCA 200 mg/kg than DCA 100 mg/kg. DCA did not change either the ATP levels or energy charge potential during both ischemia and reperfusion. LAD occlusion caused a significant decrease of myocardial pH from 7.51 to 6.83 in saline-treated group, while it produced only a small decrease in DCA-treated group from 7.56 to 7.35.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizushima
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003999:Dichloroacetic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D000085:Acetates; D000227:Adenine Nucleotides; D010725:Phosphocreatine; D003999:Dichloroacetic Acid