GLYCOGEN DEPLETION CONTRIBUTES TO ISCHEMIC PRECONDITIONING IN THE RAT-HEART IN-VIVO

Ischemic preconditioning depletes the myocardium of glycogen, thus blu nting lactic acidosis during subsequent episodes of ischemia. Precondi tioning also protects against reperfusion arrhythmias and infarction. To test whether glycogen depletion is necessary for this ischemic tole rance, we preconditioned two groups of intact rats with a series of 3- min coronary artery occlusions. In one group, preconditioning lowered the glycogen concentration of the ischemic region by similar to 50% (2 4.9 +/- 2.5 to 12.5 +/- 1.8 mu mol/g; P < 0.01). In the other, the hea rt was first loaded with glycogen via glucose-insulin infusion so that preconditioning merely reduced its glycogen concentration back to nor mal physiological levels. Compared with nonpreconditioned control rats , preconditioned rats with both normal and subnormal glycogen concentr ations were protected from reperfusion arrhythmias after a 6-min coron ary occlusion (incidence: control rats, 100%; normal glycogen rats, 11 %; reduced glycogen rats, 11%). In contrast, only rats with subnormal glycogen concentration after preconditioning exhibited reduced lactate formation and infarct size after a 45-min coronary occlusion [infarct size (percentage of risk area): control rats. 53 +/- 10%; normal glyc ogen rats, 50 +/- 16%, P = not significant; subnormal glycogen rats, 1 8 +/- 10%, P < 0.01]. Thus, in the intact rat, myocardial glycogen dep letion appears to be necessary for the infarct-limiting, but not for t he antiarrhythmic, effects of ischemic preconditioning.