Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia

During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (M(V)over dotO(2)) in response to a greater demand for oxygen, resulting in "demand-induced" ischemia. We tested the hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative glycolysis without a change in M(V)over dotO(2) or fatty acid uptake. Measurements were made in the anterior wall of anesthetized open-chest swine hearts (n=7). The left anterior descending (LAD) coronary artery flow was controlled via an extracorporeal perfusion circuit, and substrate uptake and oxidation were measured with radiotracers. Demand-induced ischemia was produced with intravenous dobutamine (15 mug.kg(-1).min(-1)) and 20% reduction in LAD flow for 20 min. Despite no change in M(V)over dotO(2), there was a switch from lactate uptake (5.9+/-3.1) to production (74.5+/-16.3 mumol/min), glycogen depletion (66%), and increased glucose uptake (105%), but no change in anterior wall power or the index of anterior wall energy efficiency. There was no change in the rate of tracer-measured fatty acid uptake; however, exogenous fatty acid oxidation decreased by 71%. Thus demand-induced ischemia stimulated nonoxidative glycolysis and lactate production, but did not effect fatty acid uptake despite a fall in exogenous fatty acid oxidation.