The effect of ischaemia on the activity of pyruvate dehydrogenase complex in rat heart.
The effect of ischaemia on the concentration of active pyruvate dehydrogenase complex has been investigated in glucose perfused hearts of normal rats fed a normal diet or a high fat diet or starved for 48 h; and in hearts from alloxan-diabetic rats. Global ischaemia induced by low flow (approx. 1 ml/min) lowered the concentration of active complex under most of the experimental conditions employed. Parallel studies showed that anoxia and K+ arrest of the heart had effects similar to that of ischaemia and suggested that hypoxia and decreased mechanical activity of the heart may be responsible for effects of low flow ischaemia. Evidence is reviewed that the effects of low flow ischaemia, K+ arrest and anoxia may be mediated through activation of pyruvate dehydrogenase kinase by increased reduction of mitochondrial NAD+. In hearts of normal rats on a normal diet, global ischaemia induced by zero flow and regional ischaemia induced by coronary artery ligation increased the concentration of active complex. Evidence is given that this may result from a combination of anoxia and acidosis. In aerobic perfusions at 60 mmHg, concentrations of active complex were ranked in the order: normal diet greater than high fat diet greater than 48 h starved greater than alloxan diabetic. This order was maintained when the concentration of active complex was increased by perfusion at 120 mmHg or lowered by global ischaemia induced by zero flow.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004041:Dietary Fats / Q000378:metabolism; D006323:Heart Arrest / Q000201:enzymology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010101:Oxygen Consumption; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000201:enzymology
D004041:Dietary Fats; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate