Glycogen turnover and anaplerosis in preconditioned rat hearts

Using C-13 NMR, we tested the hypothesis that protection by preconditioning is associated with reduced glycogenolysis during ischemia. Preconditioned rat hearts showed improved postischemic function and reduced ischemic damag e relative to ischemic controls after 30 min stop-flow ischemia and 30 min reperfusion (contractility: 30 +/- 10 vs. 2 +/- 2%; creatine kinase release : 41 +/- 4 vs. 83 +/- 15 U/g; both P < 0.05). Preconditioning decreased pre ischemic [C-13]glycogen by 24% (a 10% decrease in total glycogen), and dela yed ischemic [C-13]glycogen consumption by 5-10 min, reducing ischemic glyc ogenolysis without changing acidosis relative to controls. Upon reperfusion , glycogen synthesis resumed only after preconditioning. Glutamate C-13-iso topomer analysis showed recovery of Krebs cycle activity with higher anaple rosis than before ischemia (23 +/- 4 vs. 11 +/- 3%, P < 0.05), but in contr ols reperfusion failed to restore flux. Compared to control, preconditionin g before 20 min ischemia increased contractility (86 +/- 10 vs. 29 +/- 14%, P < 0.05) and restored preischemic anaplerosis (13 +/- 3 vs. 39 +/- 9%, P < 0.05). Preconditioning is associated with reduced glycogenolysis early du ring ischemia. However, protection does not rely on major variations in int racellular pH, as proposed earlier. Our isotopomer data suggest that precon ditioning accelerates metabolic and functional recovery during reperfusion by more efficient/active replenishment of the depleted Krebs cycle. (C) 200 0 Elsevier Science B.V. All rights reserved.