ACUTE ISCHEMIC PRECONDITIONING PROTECTS AGAINST SKELETAL-MUSCLE INFARCTION IN THE PIG

Objective: The aims were to investigate the efficacy of acute ischaemi c preconditioning for protection of skeletal muscles against infarctio n and its effect on muscle blood flow and ischaemic muscle metabolism. Methods: The efficacy of preconditioning was tested by subjecting pig latissimus dorsi and gracilis muscles to different numbers and durati ons of ischaemia/reperfusion cycles before 4 h of global ischaemia. In farction was assessed at 48 h of reperfusion, using nitroblue tetrazol ium dye. Blood flow in the latissimus dorsi was measured at the end of preconditioning and 1.5 and 3.0 h of reperfusion, using the radioacti ve microsphere (15 mu m) technique. Muscle biopsies were taken from th e latissimus dorsi before ischaemia, at the end of 2 and 4 h of ischae mia, and 1.5 h of reperfusion. Results: At least three cycles of 10 mi n ischaemia and 10 min reperfusion were required for preconditioning o f latissimus dorsi and gracilis muscles for protection against infarct ion. Preconditioning reduced the total infarct size by 44% and 62% in latissimus dorsi and gracilis muscles, respectively. Preconditioning d id not affect preischaemia muscle blood flow but it reduced the muscle content (preischaemia reserve) of phosphocreatine and ATP and the mus cle energy charge potential (ECP) by 13.5%, 27.5%*, and 8%* (*P < 0.0 5), respectively. In spite of a lower preischaemia reserve of phosphoc reatine and ATP, the muscle contents of phosphocreatine and ATP and mu scle ECP were maintained higher and the lactate lower (P less than or equal to 0.05) in the preconditioned than in the non-preconditioned ( control) muscles at the end of 4 h of ischaemia [phosphocreatine 8.0(S EM 0.4) v 3.2(0.3); ATP 9.8(0.7) v 7.8(0.3); ECP 0.72(0.02) v 0.66(0. 01); lactate 115.4(8.6) v 160.5(11.8)* mu mol . g(-1) dry muscle]. Th e level of ATP and ECP also remained significantly higher and the leve l of lactate significantly lower in the preconditioned than in the non -preconditioned latissimus dorsi muscles at 1.5 h of reperfusion. Hype raemia was seen in the preconditioned latissimus dorsi muscles at 1.5 h of reperfusion and it subsided by the end of 3h of reperfusion. Conc lusions: The protective effect of preconditioning can be induced in pi g skeletal muscle but at a higher threshold than reported previously i n pig cardiac muscle (one cycle). Preconditioning of pig skeletal musc le is associated with a lower energy metabolism during sustained ischa emia. At the present time, it is not known if this energy sparing effe ct is a major mechanism of ischaemic preconditioning against infarctio n in skeletal muscles.