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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2576    most recent 00942.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Gandhi, M. Articles by Clanachan, A. S. Search for Related Content PubMed PubMed Citation Articles by Gandhi, M. Articles by Clanachan, A. S.

Role of glucose metabolism in the recovery of postischemic LV mechanical function: effects of insulin and other metabolic modulators

Departments of ¹Pharmacology and ²Anesthesiology and Pain Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

Submitted 14 August 2007 ; accepted in final form 7 April 2008

The role of proton (H⁺) production from glucose metabolism in the recovery of myocardial function during postischemic reperfusion and its alteration by insulin and other metabolic modulators were examined. Rat hearts were perfused in vitro with Krebs-Henseleit solution containing palmitate (1.2 mmol/l) and glucose (11 mmol/l) under nonischemic conditions or during reperfusion following no-flow ischemia. Perfusate contained normal insulin (n-Ins, 50 mU/l), zero insulin (0-Ins), or supplemental insulin (s-Ins, 1,000 mU/l) or other metabolic modulators [dichloroacetate (DCA) at 3 mmol/l, oxfenicine at 1 mmol/l, and N⁶-cyclohexyladenosine (CHA) at 0.5 µmol/l]. Relative to n-Ins, 0-Ins depressed rates of glycolysis and glucose oxidation in nonischemic hearts and impaired recovery of postischemic function. Relative to n-Ins, s-Ins did not affect aerobic glucose metabolism and did not improve recovery when present during reperfusion. When present during ischemia and reperfusion, s-Ins impaired recovery. Combinations of metabolic modulators with s-Ins stimulated glucose oxidation 2.5-fold in nonischemic hearts and reduced H⁺ production. DCA and CHA, in combination with s-Ins, improved recovery of function, but addition of oxfenicine to this combination provided no further benefit. Although DCA and CHA were each partially protective in hearts perfused with n-Ins, optimal protection was achieved with DCA + CHA; recovery of function was inversely proportional to H⁺ production during reperfusion. Although supplemental insulin is not beneficial, elimination of H⁺ production from glucose metabolism by simultaneous inhibition of glycolysis and stimulation of glucose oxidation optimizes recovery of postischemic mechanical function.

proton production; ischemia-reperfusion; contractile function; rat hearts