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
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