Regulation of glycogen utilization in ischemic hearts after 24 hours of fasting

Introduction: Fasting protects the ischemic heart from injury and infarctio n. Previous studies have shown that hearts from fasted animals have greater glycogen utilization and a lower cytosolic redox state (NADH/NAD(+)) durin g global ischemia. While the mechanisms of increased glycogen utilization i n fasted animals have not been elucidated, animals that hibernate or are to lerant of anoxia are known to increase the tissue content of the active for m of glycogen phosphorylase, phosphorylase a. Therefore, this study was des igned to (a) determine whether hearts from fasted animals have increased ac tivity of glycogen phosphorylase during ischemia and (b) define those mecha nisms responsible for this increase. Methods: Hearts isolated from either f ed or fasted (24 h) rats were perfused and freeze-clamped at baseline, and after 1 and 10 min of ischemia, for measurement of phosphorylase activity, phosphorylase kinase activity, and glucose-6-phosphate concentrations. Resu lts: Fasting increased the phosphorylase a/b ratio under both baseline and ischemic conditions. This increase was not accompanied by an increase in th e activity of phosphorylase kinase, either with maximal [Ca2+] or under phy siologic [Ca2+]. Glucose 6-phosphate concentrations were lower in hearts fr om fasted animals under baseline, but not ischemic, conditions. Conclusions : Fasting enhances glycogen utilization during ischemia by increasing the a ctive form of glycogen phosphorylase. This increase is not due to a change in phosphorylation by phosphorylase kinase nor end-product inhibition by G- GP. While the precise mechanism of increased glycogen phosphorylase activit y in fasted animals is not clear, one likely explanation may be the lower c ytosolic redox state demonstrated in the myocardium of fasted animals. (C) 1999 Elsevier Science B.V. All rights reserved.