Neutrophil lipoxygenase activation and leukosequestration in
postischemic myocutaneous flaps: role of ltb4.
Kirschner, Richard E., Jerry J. C. Chiao, Billie S. Fyfe, Lloyd A.
Hoffman, John Mihran Davis, and Gary A. Fantini.
Department of Surgery, The New York Hospital and Cornell University
Medical College, New York, New York 10021; and Department of
Pathology, The Mount Sinai School of Medicine, New York, New York
10029
APStracts 2:0057H, 1995.
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 (5-LO)
activity and to define the role of leukotriene B4 (LTB4) in
postischemic PMN infiltration into such composite tissue grafts.
Anesthetized Yorkshire pigs underwent six hours 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 minutes of reperfusion, neutrophil generation
of LTB4 increased from a baseline value of 31.0 + 6.8 ng/5 X 106 PMN
to 98.5 + 5.1 ng/5 X 106 PMN (P < 0.01) and was significantly
greater than that of neutrophils isolated from animals subjected to
sham ischemia and reperfusion (54.3 + 4.1 ng/5 X 106 PMN; P <
0.01). Pretreatment of animals with the LTB4 receptor antagonist SC
-41930 (n = 5) significantly attenuated reperfusion-associated 5-LO
activation (60.3 + 11.6 ng LTB4 /5 X 106 PMN; P < 0.01),
suggesting the presence of a positive feedback mechanism for
eicosanoid biosynthesis. Graft ischemia in control animals was
associated with progressive PMN infiltration at one and four hours of
reperfusion (334 + 92 and 667.2 + 198 PMNs/25 HPF, respectively);
however, pretreatment with SC-41930 or the 5-LO inhibitor
diethylcarbamazine dramatically reduced PMN infiltration at one hour
of reperfusion (22 + 3 and 64 + 36 PMNs/25 HPF, respectively; P
< 0.01) and at four hours of reperfusion (178 + 31 and 156 + 40
PMNs/25 HPF; P < 0.01). These data indicate that myocutaneous
flap ischemia-reperfusion leads to activation of 5-LO in circulating
PMNs and suggest that LTB4 plays a critical role in the pathogenesis
of reperfusion injury by amplifying the process of neutrophil
recruitment into postischemic tissues.
Received 5 April 1994; accepted in final form 28 November 1994.
APS Manuscript Number H310-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.