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.