Ischemia-reperfusion injury in myocutaneous flaps: role of leukocytes and leukotrienes.
Leukotriene B4 is a potent inflammatory mediator that is derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and that has been implicated in the pathophysiology of polymorphonuclear leukocyte-dependent reperfusion injury in a variety of organ systems. The objectives of these investigations were to determine whether inhibition of leukotriene B4 attenuates postischemic polymorphonuclear leukocyte infiltration 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 leukotriene B4 receptor antagonist SC-41930 (n = 7). All animals underwent 6 hours of rectus abdominis myocutaneous flap ischemia followed by 4 hours of reperfusion. In saline-treated controls, flap ischemia was associated with massive polymorphonuclear leukocyte infiltration at 1 and 4 hours of reperfusion (252 +/- 70 and 619 +/- 137 polymorphonuclear leukocytes per 25 high-power fields, respectively). Skeletal muscle neutrophil content was significantly attenuated by pretreatment with diethylcarbamazine (72 +/- 29 and 229 +/- 63 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05) or SC-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 tetrazolium staining, diminished from 47.6 +/- 11.3 percent in controls to 25.1 +/- 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 B4 plays a critical role in mediating neutrophil-dependent injury in postischemic skeletal muscle flaps.
Kirschner
R E
RE
Department of Surgery, New York Hospital-Cornell Medical Center, N.Y., USA.
Fyfe
B S
BS
Hoffman
L A
LA
Chiao
J J
JJ
Davis
J M
JM
Fantini
G A
GA
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D004049:Diethylcarbamazine / Q000494:pharmacology; D005260:Female; D018836:Inflammation Mediators / Q000502:physiology; D007975:Leukotriene B4 / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000473:pathology; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013524:Surgical Flaps; D013552:Swine
D001578:Benzopyrans; D018836:Inflammation Mediators; D016859:Lipoxygenase Inhibitors; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4; D004049:Diethylcarbamazine