ROLE OF PREISCHEMIC GLYCOGEN DEPLETION IN THE IMPROVEMENT OF POSTISCHEMIC METABOLIC AND CONTRACTILE RECOVERY OF ISCHEMIA-PRECONDITIONED RATHEARTS

Background Ischemic preconditioning (IPC) attenuates acidosis during p rolonged ischemia and improves contractile and metabolic parameters du ring subsequent reperfusion. Glycogen depletion induced by IPC is prop osed as a potential mechanism. Methods and Results We studied the infl uence of manipulations of preischemic glycogen levels (Pre-G, mu mol g lucose/g wet wt) on contractile and metabolic (via P-31-nuclear magnet ic resonance) parameters during 30 minutes of ischemia and recovery in four groups of isovolumic rat hearts: First, control (Con, n=18, mean Pre-G, 21.5+/-0.8); second, after two 5-minute IPC periods (IPC, n=12 , Pre-G, 11.3+/-0.7); third, a control group in which Pre-G was deplet ed by glucose-free, acetate perfusion (Con-LowG, n=9, Pre-G, 7.9+/-1.2 ); and fourth, an IPC group in which Pre-G was raised by glucose and l actate perfusion such that Pre-G was similar to Con (IPC-HiG, n=11, Pr e-G, 20+/-1.4). Manipulation of Pre-G significantly altered the pH fal l during 30 minutes of ischemia (Con, 5.76+/-.03, Con-LowG, 6.26+/-.07 ; IPC-HiG, 5.91+/-.02, IPC, 6.05+/-.09). IPC-HiG hearts had significan tly worse metabolic recovery (PCr, 70+/-7 Versus 91+/-3% initial; IPC- HiG Versus IPC, P<.05) and contractile recovery (end-diastolic pressur e, 52+/-5 versus 29+/-5 mm Kg, P<.05) than IPC hearts but better recov ery than Con (%PCr, 56+/-6% and end-diastolic pressure, 72+/-6 mm Hg). An ischemic rise in intracellular magnesium occurred and was atttenua ted in preconditioned hearts. Conclusions Pre-G levels before ischemia influence but are not the sole determinants of the extent of acidosis during prolonged ischemia and of metabolic and contractile recovery d uring reperfusion in control and preconditioned hearts.