JACC Vol. 13, No. 3 March I, 1989:745-54 745 Sustained Nonoxidative Glucose Utilization and Depletion of Glycogen in Reperfused Canine Myocardium zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE MARKUS SCHWAIGER, MD, RICHARD A. NEESE,* PHD, LOUIS ARAUJO, MD, WILLIAM WYNS, MD, JUDITH A. WISNESKI,* MD, FACC, HEINZ SOCHOR, MD, STANLEY SWANK,t MS, DAVID KULBER,t CARL SELIN, MS, MICHAEL PHELPS, PHD, HEINRICH R. SCHELBERT, MD, FACC, MICHAEL C. FISHBEIN,t MD, EDWARD W. GERTZ,” MD, FACC, WITH THE TECHNICAL ASSISTANCEOF HERBERT HANSEN zyxwvutsrqpon Los Angeles and San Francisco, California Ischemically injured reperfused myocardium is character- ized by increased 18F-lluorodeoxyglucose uptake as demon- strated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-r4C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocar- dium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemi- cal evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 f 0.14 versus 0.15 + 0.10 ~mol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly in- creased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon- labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exoge- nous glucose contributed to >90% of the observed lactate production. This finding was confirmed by the histochem- ical finding of sustained glycogen depletion in the occlusion/ reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%). These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose be- comes an important myocardial substrate under these pathologic conditions. (J Am Co11 Cardiol1989;13:745- 54) Reperfusion to salvage ischemically injured myocardium has recently become the focus of experimental and clinical research (l-5). It is known that regional myocardial function From the *Division of Cardiology, University of California and the Veterans Administration Medical Center of San Francisco, San Francisco. tDepartment of Pathology, Cedars Sinai Medical Center and Division of Nuclear Medicine and Biophysics. Department of Radiological Sciences and Laboratory of Nuclear Medicine, Laboratory of Biomedical and Environmen- tal Sciences, University of California at Los Angeles School of Medicine, Los Angeles, California. The Laboratory of Biomedical and Environmental Sci- ences is operated for the United States Department of Energy by the University of California under contract no. DE-AC03-76-SFOOOl2. This work was supported in part by the Director of the Office of Energy Research, Office of Health and Environmental Research, Los Angeles, California; by Grants HL 29845. HL 33177and HL 25625from the National Institutes of Health, remains impaired for a prolonged period after ischemia, even in reversibly injured myocardium (6). In addition, it has been shown that the delayed functional recovery is paralleled by a sustained decrease in the tissue concentration of high energy phosphate, indicating abnormalities in myocardial energy Bethesda, Maryland; Medical Research Service of the Veterans Administra- tion, Washington, D.C. and by an Investigative Group Award of the American Heart Association, Greater Los Angeles Affiliate, Los Angeles. Manuscript received December 28, 1987: revised manuscript received July 20, 1988, accepted October 9, 1988. Address for renrints: Markus Schwaiger, MD, Department of Internal Medicine, Division of Nuclear Medicine, University of Michigan Medical Center, 1500 East Medical Center Drive, UH Bl G505iOO28, Ann Arbor, Michigan 48109-0028. 01989 by the American College of Cardiology 0735-lOY7/89/$3.50