Neutrophil lipoxygenase activation and leukosequestration in postischemic myocutaneous flaps: role of LTB4.
Reperfusion of ischemic tissues leads to eicosanoid- and polymorphonuclear leukocyte (PMN)-dependent injury. The present experiments were undertaken to examine the effect of myocutaneous flap ischemia-reperfusion on neutrophil 5-lipoxygenase activity and to define the role of leukotriene B4 (LTB4) in postischemic PMN infiltration into such composite tissue grafts. Anesthetized Yorkshire pigs underwent 6 h of rectus abdominis myocutaneous flap ischemia or sham ischemia, and LTB4 generation was measured in calcium ionophore-stimulated neutrophils isolated from the circulation. At 30 min of reperfusion, neutrophil generation of LTB4 increased from a baseline value of 31.0 +/- 6.8 to 98.5 +/- 5.1 ng/5 x 10(6) PMN (P < 0.01) and was significantly greater than those neutrophils isolated from animals subjected to sham ischemia and reperfusion (54.3 +/- 4.1 ng/5 x 10(6) PMN; P < 0.01). Pretreatment of animals with the LTB4-receptor antagonist, SC-41930 (n = 5), significantly attenuated reperfusion-associated 5-lipoxygenase activation (60.3 +/- 11.6 ng LTB4/5 x 10(6) PMN; P < 0.01), suggesting the presence of a positive feedback mechanism for eicosanoid biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Kirschner
R E
RE
Department of Surgery, New York Hospital and Cornell University Medical College 10021, USA.
Chiao
J J
JJ
Fyfe
B S
BS
Hoffman
L A
LA
Davis
J M
JM
Fantini
G A
GA
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood*; D001578:Benzopyrans / Q000494:pharmacology; D001794:Blood Pressure; D004789:Enzyme Activation; D005260:Female; D006339:Heart Rate; D007511:Ischemia / Q000097:blood / Q000503:physiopathology*; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D016859:Lipoxygenase Inhibitors; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D015424:Reperfusion; D012867:Skin / Q000098:blood supply*; D013524:Surgical Flaps; D013552:Swine
D001578:Benzopyrans; D016859:Lipoxygenase Inhibitors; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase