ISCHEMIA-REPERFUSION INJURY IN MYOCUTANEOUS FLAPS - ROLE OF LEUKOCYTES AND LEUKOTRIENES

Leukotriene B-4 is a potent inflammatory mediator that is derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and that ha s been implicated in the pathophysiology of polymorphonuclear leukocyt e-dependent reperfusion injury in a variety of organ systems. The obje ctives of these investigations were to determine whether inhibition of leukotriene B-4 attenuates postischemic polymorphonuclear leukocyte i nfiltration and subsequent injury in myocutaneous flaps. Anesthetized female Yorkshire pigs were randomized to receive normal saline (n = 8) , the 5-lipoxygenase inhibitor diethylcarbamazine (n = 7), or the leuk otriene B-4 receptor antagonist SC-41930 (n = 7). All animals underwen t 6 hours of rectus abdominis myocutaneous flap ischemia followed by 4 hours of reperfusion. In saline-treated controls, flap ischemia was a ssociated with massive polymorphonuclear leukocyte infiltration at 1 a nd 4 hours of reperfusion (252 +/- 70 and 619 +/- 137 polymorphonuclea r leukocytes per 25 high-power fields, respectively). Skeletal muscle neutrophil content was significantly attenuated by pretreatment with d iethylcarbamazine (72 +/- 29 and 229 +/- 63 polymorphonuclear leukocyt es per 25 high-power fields; p < 0.05) or SG-41930 (25 +/- 3 and 193 /- 25 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05) . Wet-to-dry weight ratios of full-thickness flap biopsies were lower in the diethylcarbamazine and SC-41930 groups (2.98 +/- 0.15 and 2.90 +/- 0.26, respectively) than in the control group (4.13 +/- 0.23; p < 0.01), and mean muscle infarct size, as determined by nitroblue tetraz olium staining, diminished from 47.6 +/- 11.3 percent in controls to 2 5.1 +/- 6.5 percent in diethylcarbamazine-treated animals and 7.3 +/- 4.8 percent in SC41930-treated animals (P < 0.05). These data indicate that leukotriene B-4 plays a critical role in mediating neutrophils-d ependent injury in postischemic skeletal muscle flaps.