Dichloroacetate as metabolic therapy for myocardial ischemia and failure.
Am Heart J
; 134(5 Pt 1): 841-55, 1997 Nov.
Article
em En
| MEDLINE
| ID: mdl-9398096
ABSTRACT
This article critically reviews the pharmacologic effects of the investigational drug dichloroacetate (DCA), which activates the mitochondrial pyruvate dehydrogenase enzyme complex in cardiac tissue and thus preferentially facilitates aerobic oxidation of carbohydrate over fatty acids. The pharmacologic effects of DCA are compared with other interventions, such as glucose plus insulin, inhibitors of long chain fatty acid oxidation and adenosine, that are also thought to exert their therapeutic effects by altering myocardial energy metabolism. Short-term clinical and laboratory experiments demonstrate that intravenous DCA rapidly stimulates pyruvate dehydrogenase enzyme complex activity and, therefore, aerobic glucose oxidation in myocardial cells. Typically these effects are associated with suppression of myocardial long chain fatty acid metabolism and increased left ventricular stroke work and cardiac output without changes in coronary blood flow or myocardial oxygen consumption. Although long-term studies are lacking, short-term parenteral administration of DCA appears to be safe and capable of significantly improving myocardial function in conditions of limited oxygen availability by increasing the efficient conversion of myocardial substrate fuels into energy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Dicloroacético
/
Metabolismo Energético
/
Coração
/
Miocárdio
Limite:
Humans
Idioma:
En
Revista:
Am Heart J
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos