POLYMORPHONUCLEAR LEUKOCYTES INCREASE REPERFUSION INJURY IN SKELETAL-MUSCLE

Objective. To study the effect of polymorphonuclear leucocytes (PMNLs) on reperfusion injury in rabbit skeletal muscle and to evaluate the r ole of oxygen-derived free radicals in PMNL-mediated reperfusion injur y. Experimental design. An isolated rabbit limb perfusion model. Amput ated hindlimbs were subjected to 4 hours of ischaemia followed by 2 ho urs of reperfusion with oxygenated Krebs' buffer. Setting. Department of experimental surgery. Animals. 14 rabbits. Interventions. In group I (n=8), one limb from each animal was reperfused with PMNL-supplement ed buffer while the other limb was reperfused with cell-free buffer (c ontrol). In group II (n=6), SOD and catalase were added to the limb re perfused with PMNL-supplemented buffer while the other limb was reperf used with cell-free buffer without SOD and catalase (control). Measure s. PMNL accumulation as myeloperoxidase (MPO) activity, muscle necrosi s as uptake of [Tc-99]methylenediphosphonate (MDP), and oedema as incr ease in muscle water content (MDP). Electron microscopy was performed for histological demonstration of reperfusion injury. Results. Additio n of PMNLs increased MPO activity (p<0.05) and MDP uptake (p<0.05) but did not affect MWC. SOD and catalase treatment of limbs perfused with PMNLs prevented the increase in MPO activity (p<0.05) and reduced MDP uptake (p<0.05) and MWC (p<0.05). PMNLs aggravated histological chang es seen after reperfusion. Conclusions. Reperfusion injury in skeletal muscle is, at least partially, mediated by PMNLs. Free radical scaven gers reduce PMNL-dependent injury and prevent PMNL accumulation sugges ting that oxygen-derived free radicals are mediators of PMNL-dependent injury and/or engaged in the interaction between PMNLs and the microv ascular endothelium.