title: Ischemic preconditioning inhibits glycolysis and proton production in isolated working rat hearts.
abstract: The effect of ischemic preconditioning (IPC) on glycolysis, glucose oxidation, adenine nucleotide and nucleoside levels, and mechanical function was studied in isolated paced working rat hearts under aerobic conditions or when reperfused following sustained ischemia. IPC inhibited glycolysis in aerobic hearts (4.48 +/- 0.66 vs. 3.18 +/- 0.39 mumol.min-1.g dry wt-1) and calculated proton production attributable to exogenous glucose (7.79 +/- 1.31 vs. 4.73 +/- 0.81 mumol.min-1.g dry wt-1). In hearts subjected to ischemia and reperfusion, IPC decreased, relative to controls, glycogen content before the onset of ischemia (116.6 +/- 4.3 vs. 158.0 +/- 8.4 mumol/dry wt) and decreased consumption of glycogen during ischemia (54 +/- 6 vs. 76 +/- 7 mumol/dry wt). During reperfusion, glycolysis was lower in IPC hearts (2.45 +/- 0.16 vs. 4.4 +/- 0.46 mumol.min-1.g dry wt-1), as was calculated proton production (3.57 +/- 0.30 vs. 8.38 +/- 0.93 mumol.min-1.g dry wt-1). Glucose oxidation was similar in control and IPC hearts. Adenosine and ATP content of IPC hearts, relative to controls, were higher at the end of ischemia, being 0.86 +/- 0.08 vs. 0.34 +/- 0.15 mumol/g dry wt and 11.3 +/- 0.8 vs. 5.0 +/- 1.6 mumol/g dry wt, respectively. IPC enhanced recovery of ventricular work during reperfusion of ischemic hearts from 37 to 68%. These results indicate that IPC is associated with a reduction in glycogen content, inhibition of glycolysis during ischemia and reperfusion, and a decrease in proton production from glucose. These changes may, in part, explain the enhanced recovery of mechanical function observed in IPC hearts.
authors.affiliation: Department of Anesthesia, Faculty of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: B A
authors.initials: BA
authors.lastname: Finegan
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: M
authors.initials: M
authors.lastname: Gandhi
authors.forename: A S
authors.initials: AS
authors.lastname: Clanachan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D002304:Cardiac Pacing, Artificial; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007773:Lactates; D011522:Protons; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose