Protective Role of Increased Myocardial Glycogen Stores in Cardiac Anoxia in the Rat

Abstract

To determine whether increased glycogen stores might protect the heart against anoxia, experiments were performed in the isolated perfused rat heart. Marked differences in cardiac glycogen were produced by comparing hearts from rats previously treated with reserpine with hearts from control rats. Lesser differences in cardiac glycogen were produced in hearts by perfusing them for 15 minutes without glucose (0 mM glucose) or with 20 mM glucose. Both groups were then studied during a 5-minute anoxic cycle with 5 mM glucose as the exogenous substrate. Hearts from the reserpine-treated rats had higher left ventricular pressures, maximal rate of left ventricular pressure rise, and lactate output after 2 minutes of anoxia than the hearts from control rats. Similar but less marked mechanical differences were observed between 0 mM glucose and 20 mM glucose hearts. The mechanical differences during anoxia between the two groups were not abolished by simultaneous L-norepinephrine administration. Hearts with greater initial glycogen stores had higher glycogenolytic rates, and proportionately more lactate was produced from glycogen than from glucose. Thus, anaerobic ATP production per mole of hexose was greater in hearts with higher glycogen stores. Calculated ATP production was also greater in hearts from the reserpine-treated rats than in those from control animals. These studies demonstrate that both marked and minor elevations in cardiac glycogen are associated with greater glycolytic reserve and improved mechanical resistance to anoxia. This appears to be mainly due to enhanced glycogenolysis and anaerobic ATP production.