LOSS OF GLYCOGEN DURING PRECONDITIONING IS NOT A PREREQUISITE FOR PROTECTION OF THE RABBIT HEART

Depletion of gycogen has been proposed as the mechanism of protection from ischemic preconditioning. The hypothesis was tested by seeing whe ther pharmacological manipulation of preconditioning causes parallel c hanges in cardiac glycogen content. Five groups of isolated rabbit hea rts were studied. Group 1 experienced 30 min of ischemia only. Group 2 (PC) was preconditioned with 5 min of global ischemia followed by 10 min of reperfusion. Group 3 was preconditioned with 5 min exposure to 400 nM bradykinin followed by a 10 min washout period. Group 3 experie nced exposure to 10 mu M adenosine followed by a 10 min washout period , and the fifth group was also preconditioned with 5 min ischemia and 10 min reperfusion but 100 mu M 8-(p-sulfophenyl)theophylline (SPT), w hich blocks adenosine receptors, was included in the buffer to block p reconditioning's protection. Transmural biopsies were taken before tre atment, just prior to the 30 min period of global ischemia, and after 30 min of global ischemia. Glycogen in the samples was digested with a myloglucosidase and the resulting glucose was assayed. Baseline glycog en averaged 17.3 +/- 0.6 mu mol glucose/g wet weight. After preconditi oning glycogen decreased to 13.3 +/- 1.3 mu mol glucose/g wet weight ( p < 0.005 vs. baseline). Glycogen was similarly depleted after pharmac ological preconditioning with adenosine (14.0 +/- 1.0 mu mol glucose/g wet weight, p < 0.05 vs. baseline) suggesting a correlation. However, when preconditioning was performed in the presence of SPT, which bloc ks protection, glycogen was also depleted by the same amount (13.3 +/- 0.7 mu mol glucose/g wet weight, p = ns vs. PC). Bradykinin, which al so mimics preconditioning, caused no depletion of glycogen (16.3 +/- 0 .8 mu mol glucose/g wet weight, p = ns vs. baseline). Because precondi tioning with bradykinin did not deplete glycogen and because glycogen continued to be low when protection from preconditioning was blocked w ith SPT, we conclude that loss of glycogen per se does not cause the p rotection of preconditioning.