Loss of glycogen during preconditioning is not a prerequisite for protection of the rabbit heart.

Depletion of glycogen has been proposed as the mechanism of protection from ischemic preconditioning. The hypothesis was tested by seeing whether pharmacological manipulation of preconditioning causes parallel changes in cardiac glycogen content. Five groups of isolated rabbit hearts 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 4 experienced exposure to 10 microM 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 microM 8-(p-sulfophenyl)theophylline (SPT), which blocks adenosine receptors, was included in the buffer to block preconditioning's protection. Transmural biopsies were taken before treatment, just prior to the 30 min period of global ischemia, and after 30 min of global ischemia. Glycogen in the samples was digested with amyloglucosidase and the resulting glucose was assayed. Baseline glycogen averaged 17.3 +/- 0.6 mumol glucose/g wet weight. After preconditioning glycogen decreased to 13.3 +/- 1.3 mumol glucose/g wet weight (p < 0.005 vs. baseline). Glycogen was similarly depleted after pharmacological preconditioning with adenosine (14.0 +/- 1.0 mumol glucose/g wet weight, p < 0.05 vs. baseline) suggesting a correlation. However, when preconditioning was performed in the presence of SPT, which blocks protection, glycogen was also depleted by the same amount (13.3 +/- 0.7 mumol glucose/g wet weight, p = ns vs. PC). Bradykinin, which also mimics preconditioning, caused no depletion of glycogen (16.3 +/- 0.8 mumol glucose/g wet weight, p = ns vs. baseline). Because preconditioning with bradykinin did not deplete glycogen and because glycogen continued to be low when protection from preconditioning was blocked with SPT, we conclude that loss of glycogen per se does not cause the protection of preconditioning.