PARADOXICAL EFFECT OF ISCHEMIC PRECONDITIONING ON ISCHEMIC CONTRACTURE - NMR-STUDIES OF ENERGY-METABOLISM AND INTRACELLULAR PH IN THE RAT-HEART

Using the blood-perfused rat heart, we have previously shown that alth ough ischemic preconditioning (PC) and cardioplegia (CP) afforded simi lar protection against post-ischemic contractile dysfunction this effe ct was not additive even though PC accelerated whereas CP delayed isch emic contracture. Using NMR we examined the effects of these intervent ions on pHi and ATP metabolism during global ischemia, Isolated rat he arts (n=6/group) with an intraventricular balloon were aerobically per fused with buffer, subjected to zero now ischemia (37 degrees C) for 3 5 min and reperfused for 40 min. The groups were: (1) controls without protection, (2) PC (2 cycles), and (3) St Thomas' cardioplegia, prior to test ischemia, PC accelerated whereas CP delayed ischemic contract ure (P<0.05 v controls), Yet, after 40 min reperfusion, both intervent ions produced substantial improvements in the recovery of LVDP (P<0.05 v controls). During 35 min ischemia, the decline of ATP was delayed b y CP but accelerated by PC (P<0.05 v controls). The pHi fell steeply i n controls to a plateau of 5.9 after 14 min ischemia. PC had no effect on the rate of fall of pHi but reduced its extent (P<0.05). CP delaye d the onset of the decline in pHi (P<0.05) but, once initiated, there was no effect on the rate of decline to a plateau, Thus, despite prote cting post-ischemic contractile function. PC accelerated ischemic cont racture and the depletion of ATP, but substantially reduced intracellu lar acidosis. In contrast, CP slowed ischemic contracture and the depl etion of ATP; it also delayed the onset of acidosis. (C) 1996 Academic Press Limited