ROLE OF LIPID MEDIATORS IN THE PATHOGENESIS OF SKELETAL-MUSCLE INFARCTION AND EDEMA DURING REPERFUSION AFTER ISCHEMIA

During revascularization of skeletal muscle lipid mediators are releas ed that may have a role in the pathogenesis of reperfusion injury. Thi s study investigated the efficacy of the lipid mediator antagonists U7 4500A (a lipid peroxidation inhibitor), GR32191 (a thromboxane A(2) re ceptor antagonist) and SC41930 (a leukotriene B-4 (LTB(4)) receptor an tagonist) in altering muscle viability and oedema, in a rat hindlimb m odel of 6-h. ischaemia and 4-h reperfusion. Study groups comprised nor mal, ischaemic (6-h ischaemia) and control rats, and animals receiving the lipid mediator antagonists. Ischaemia itself did not result in mu scle oedema or necrosis but both occurred following reperfusion (P < 0 .01). Muscle viability was preserved by all lipid mediator antagonists (P < 0.01 versus controls, P not significant versus normal and ischae mia), with the LTB(4) receptor antagonist ameliorating limb oedema (P < 0.01 versus controls). These results demonstrate a role for lipid me diators in reperfusion injury and suggest that their antagonists might aid the management of acute limb ischaemia.