ATTENUATED GLYCOGENOLYSIS REDUCES GLYCOLYTIC CATABOLITE ACCUMULATION DURING ISCHEMIA IN PRECONDITIONED RAT HEARTS

Prior transient episodes of ischemia (''ischemic preconditioning'') re duce lactate accumulation and attenuate acidosis during a subsequent p rolonged ischemic insult. The mechanisms responsible for attenuated gl ycolytic catabolite accumulation have not been established but may inc lude earlier exhaustion of glycogen stores, slowed glycogenolysis befo re complete glycogen depletion, and/or inhibition of glycolysis. Simul taneous repeated measures of myocardial glycogen and the rates of glyc olysis, glycogenolysis, glucose utilization, and glycolytic ATP produc tion were obtained during total ischemia by C-13 nuclear magnetic reso nance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [C-13]glycolytic and [C-13]glycogenolytic rates were sig nificantly lower during total ischemia in preconditioned compared with control hearts (0.77+/-0.04 versus 1.06+/-0.06 mu mol/min per gram we t weight [P < .01] for glycolysis and 0.15+/-0.07 versus 0.78+/-0.12 m u mol/min per gram wet weight [P < .001] for glycogenolysis, respectiv ely, at 2.5 minutes of ischemia). Slowed glycolysis was present even d uring the early minutes of ischemia, when significant amounts of avail able [C-13]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the red uction in glycolysis and occurred despite an increase in glucose utili zation in preconditioned hearts (2.23+/-0.15 versus 1.5+/-0.10 mu mol/ min per gram wet weight at 1.25 minutes, P < .01). During early ischem ia, conversion of glycogen phosphorylase to the a or ''active'' form w as less in preconditioned than in control hearts (29.1+/-2.6% versus 4 1.2+/-9.8%, respectively; P < .05). Taken together, these findings dem onstrate that ischemic preconditioning significantly depresses glycoly tic catabolite accumulation during sustained ischemia not by more seve re glycolytic inhibition or exhaustion of glycogen stores but by depre ssed glycogenolysis from the onset of ischemia.