Regulation of pyruvate dehydrogenase complex activity during myocardial ischemia.
The effect of ischemia on the concentration of active pyruvate dehydrogenase (PDH) complex has been investigated in glucose-perfused hearts of normal rats fed a normal diet or a high-fat diet or starved for 48 hr and in hearts from alloxan-diabetic rats. Global ischemia induced by low flow (approximately equal to 1 ml/min) lowered the concentration of active complex under most conditions employed. Parallel studies of the effect of anoxia and of potassium arrest of the heart indicated that the effect of low-flow ischemia may result from decreased mechanical activity of the heart as a consequence of tissue hypoxia; the enzymatic mechanism may be activation of PDH kinase by increased reduction of mitochondrial NAD. In hearts of normal rats fed a normal diet, global ischemia induced by zero flow increased the concentration of active complex. Evidence is given that this may result from a combination of anoxia and acidosis. In aerobic perfusions, concentrations of active complex were ranked in the order: normal diet greater than high-fat diet greater than 48-hr starved greater than alloxan-diabetic. This order was maintained when the concentration of active complex was lowered by global ischemia induced by zero flow.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004041:Dietary Fats / Q000008:administration & dosage; D006324:Heart Arrest, Induced; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D011768:Pyruvate Dehydrogenase Complex; D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011188:Potassium