ISCHEMIC PRECONDITIONING INHIBITS GLYCOLYSIS AND PROTON PRODUCTION INISOLATED WORKING RAT HEARTS

The effect of ischemic preconditioning (IPC) on glycolysis, glucose ox idation, adenine nucleotide and nucleoside levels, and mechanical func tion was studied in isolated paced working rat hearts under aerobic co nditions or when reperfused following sustained ischemia. IPC inhibite d glycolysis in aerobic hearts (4.48 +/- 0.66 vs. 3.18 +/- 0.39 mu mol . min(-1). g dry wt(-1)) and calculated proton production attributabl e to exogenous glucose (7.79 +/- 1.31 vs. 4.73 +/- 0.81 mu mol . min(- 1). g dry wt(-1)). In hearts subjected to ischemia and reperfusion, IP C decreased, relative to controls, glycogen content before the onset o f ischemia (116.6 +/- 4.3 vs. 158.0 +/- 8.4 mu mol/dry wt) and decreas ed consumption of glycogen during ischemia (54 +/- 6 vs. 76 +/- 7 mu m ol/dry wt). During reperfusion, glycolysis was lower in IPC hearts (2. 45 +/- 0.16 vs. 4.4 +/- 0.46 mu mol . min(-1). g dry wt(-1)), as was c alculated proton production (3.57 +/- 0.30 vs. 8.38 +/- 0.93 mu mol . min(-1). g dry wt(-1)). Glucose oxidation was similar in control and I PC hearts. Adenosine and ATP content of IPC hearts, relative to contro ls, were higher at the end of ischemia, being 0.86 +/- 0.08 vs. 0.34 /- 0.15 mu mol/g dry wt and 11.3 +/- 0.8 vs. 5.0 +/- 1.6 mu mol/g dry wt, respectively. IPC enhanced recovery of ventricular work during rep erfusion of ischemic hearts from 37 to 68%. These results indicate tha t IPC is associated with a reduction in glycogen content, inhibition o f glycolysis during ischemia and reperfusion, and a decrease in proton production from glucose. These changes may, in part, explain the enha nced recovery of mechanical function observed in IPC hearts.