Attenuated Glycogenolysis Reduces Glycolytic Catabolite Accumulation During Ischemia in Preconditioned Rat Hearts

Abstract

Prior transient episodes of ischemia ("ischemic preconditioning") reduce lactate accumulation and attenuate acidosis during a subsequent prolonged ischemic insult. The mechanisms responsible for attenuated glycolytic catabolite accumulation have not been established but may include earlier exhaustion of glycogen stores, slowed glycogenolysis before complete glycogen depletion, and/or inhibition of glycolysis. Simultaneous repeated measures of myocardial glycogen and the rates of glycolysis, glycogenolysis, glucose utilization, and glycolytic ATP production were obtained during total ischemia by 13C nuclear magnetic resonance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [13C]glycolytic and [13C]glycogenolytic rates were significantly lower during total ischemia in preconditioned compared with control hearts (0.77 +/- 0.04 versus 1.06 +/- 0.06 mumol/min per gram wet weight [P < .01] for glycolysis and 0.15 +/- 0.07 versus 0.78 +/- 0.12 mumol/ min per gram wet weight [P < .001] for glycogenolysis, respectively, at 2.5 minutes of ischemia). Slowed glycolysis was present even during the early minutes of ischemia, when significant amounts of available [13C]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the reduction in glycolysis and occurred despite an increase in glucose utilization in preconditioned hearts (2.23 +/- 0.15 versus 1.5 +/- 0.10 mumol/min per gram wet weight at 1.25 minutes, P < .01). During early ischemia, conversion of glycogen phosphorylase to the a or "active" form was less in preconditioned than in control hearts (29.1 +/- 2.6% versus 41.2 +/- 9.8%, respectively; P < .05). Taken together, these findings demonstrate that ischemic preconditioning significantly depresses glycolytic catabolite accumulation during sustained ischemia not by more severe glycolytic inhibition or exhaustion of glycogen stores but by depressed glycogenolysis from the onset of ischemia.

Ischemic pre and postconditioning in skeletal muscle injury produced by ischemia and reperfusion in rats

“…Thus, preconditioning, as well as its association with postconditioning prevented the depletion of glycogen storage caused by ischemic process. These results are similar to those of Weiss et al 22 and Pescador et al 23 . The exact molecular mechanism to explain this phenomenon is yet to be understood.…”

Myocardial autophagic energy stress responses—macroautophagy, mitophagy, and glycophagy

“…The role of myocardial glycogen breakdown in the cardioprotection observed with preconditioning is controversial: one study reported that ischemic preconditioning attenuated glycogenolysis in rat hearts (99), whereas another study showed that 24-h in vivo fasting resulted in increased glycogen content and greater glycogen utilization during ischemia/reperfusion in a Langendorff model (80), attributed to activation of phosphorylase a (94). Interestingly, it was also observed that insulin pretreatment increased glycogen content to a similar extent but suppressed glycogen utilization during ischemia/reperfusion, resulting in increased injury and function (80).…”

Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism

“…36,37,42,43 Diazoxide is also shown to significantly reduce intracellular acidification during ischemia. Attenuation of the decline in pH i during ischemia has been attributed to (1) inhibition of H ϩ production secondary to a reduction in glycolysis or glycogenolysis 43 or, alternatively, to preischemic glycogen depletion, and (2) increased H ϩ extrusion to the extracellular space, lowering pHo but attenuating the intracellular acidification. However, arguing against the hypothesis that preconditioning enhances H ϩ extrusion, Gabel et al 42 found that preconditioning attenuated the fall in both pHi and pHo.…”