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.