THE ROLE OF LEUKOTRIENES IN CONTROLLING POSTISCHEMIC SKELETAL-MUSCLE FUNCTION

This study investigates the role of leukotrienes in controlling postis chemic alterations in skeletal muscle edema and viability. In a rodent model of six-hour unilateral hindlimb ischemia and four-hour reperfus ion, gastrocnemius muscle edema (GME, wet:dry weight ratio) and viabil ity (GMV, nitroblue tetrazolium) were assessed and indices calculated to compare results from the reperfused limb with those from the contra lateral normal limb. The influence of leukotrienes B4 (LTB4) and C4D4E 4 (peptidoleukotrienes, PLT) on these changes was assessed by employin g specific receptor antagonists (RA) to these mediators, infused intra venously from thirty minutes prior to and throughout reperfusion. Norm al (N; ten-hour general anesthesia, no ischemia) and ischemic animals (I; six-hour ischemia only) did not develop either muscle edema or nec rosis (GME--N: 1.00 [0.98-1.01], I: 1.01 [0.99-1.03]; GMV-N: 1.00 [1.0 0-1.00], I: 1.00 [1.00-1.00]) while control animals (C; ischemia and r eperfusion alone) demonstrated both (GME: 1.23 [1.09-1.37]; GMV: 0.53 [0.33-0.61]; P<0.01 vs N,I). In rats receiving the LTB4 RA (SC 41930, 1 mg/kg) muscle viability was preserved, GMV: 1.00 (1.00-1.00), P<0.01 vs C and muscle edema reduced (GME: 1.08 [1.05-1.10], P<0.01 vs C). I n contrast the PLT RA (ICI 198615, 550 mug/kg) promoted a further dete rioration in viability (GMV. 0.29 [0.17-0.33], P<0.05 vs C; P<0.01 vs N,I) with no amelioration of edema (GME: 1.26 [1.20-1.31], ns vs C). T hese results demonstrate that postischemic skeletal muscle injury is c ontrolled by leukotrienes, with PLT having a beneficial role and LTB4 appearing to enhance reperfusion injury.