Document Detail

Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs.
MedLine Citation:
PMID:  2095718     Owner:  NLM     Status:  MEDLINE    
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.
K Sakai; K Ichihara; Y Nasa; M Kamigaki; Y Abiko
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives internationales de pharmacodynamie et de thérapie     Volume:  307     ISSN:  0003-9780     ISO Abbreviation:  Arch Int Pharmacodyn Ther     Publication Date:    1990 Sep-Oct
Date Detail:
Created Date:  1991-07-08     Completed Date:  1991-07-08     Revised Date:  2012-01-12    
Medline Journal Info:
Nlm Unique ID:  0405353     Medline TA:  Arch Int Pharmacodyn Ther     Country:  BELGIUM    
Other Details:
Languages:  eng     Pagination:  92-108     Citation Subset:  IM    
Department of Pharmacology, Asahikawa Medical College, Japan.
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MeSH Terms
Acidosis / drug therapy*,  metabolism
Adenosine Triphosphate / metabolism
Coronary Disease / drug therapy,  metabolism*
Dichloroacetate / pharmacology*
Energy Metabolism / drug effects
Fatty Acids, Nonesterified / metabolism
Heart / drug effects*
Hydrogen-Ion Concentration
Lactates / metabolism
Lactic Acid
Myocardium / metabolism*
Phosphocreatine / metabolism
Pyruvates / metabolism
Pyruvic Acid
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Lactates; 0/Pyruvates; 127-17-3/Pyruvic Acid; 13425-80-4/Dichloroacetate; 50-21-5/Lactic Acid; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine

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