title: Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia.
abstract: During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (MVO(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 MVO(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 microg x kg(-1) x min(-1)) and 20% reduction in LAD flow for 20 min. Despite no change in MVO(2), there was a switch from lactate uptake (5.9 +/- 3.1) to production (74.5 +/- 16.3 micromol/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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.forename: Hazel
authors.initials: H
authors.lastname: Huang
authors.forename: Tracy A
authors.initials: TA
authors.lastname: McElfresh
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D003331:Coronary Vessels / Q000503:physiopathology; D004280:Dobutamine / Q000008:administration & dosage; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006439:Hemodynamics; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D013552:Swine; D014280:Triglycerides / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D019344:Lactic Acid; D004280:Dobutamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen