Effects of dichloroacetate on the mechanical function of the isolated ischemic heart.
The effects of sodium dichloroacetate (DCA) on the activity of the pyruvate dehydrogenase complex (PDH) and the mechanical function of the isolated ischemic rat heart were investigated. Ischemia was induced by restriction of coronary flow. Perfusion with DCA caused a decrease in the tension developed (DT) and the maximal rate of tension development (+ dT/dt max), and an increase in the resting tension (RT) at low flow rates (0.6 and 0.15 ml/min). However, it did not affect the DT or +dT/dt max of normoxic hearts (3 ml/min) or hearts at zero flow rate. DCA increased PDH activity in hearts at all flow rates. It was concluded that this effect of DCA was associated with a decrease in lactate production, rather than an increase in the lactate/pyruvate ratio.
Matsuoka
S
S
Department of Pediatrics, School of Medicine, Tokushima University, Japan.
Toshima
K
K
Naito
E
E
Nakatsu
T
T
Miyauchi
Y
Y
Kuroda
Y
Y
Miyao
M
M
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats
D000085:Acetates; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid