In vivo correlation of neutrophil receptor expression, ischemia-reperfusion injury, and selective 5-lipoxygenase inhibition in guinea pigs.
OBJECTIVE
To determine whether selective 5-lipoxygenase (5-LO) inhibition decreases expression of adhesion molecules (beta2 integrins) on systemic neutrophils, decreases neutrophil infiltration in ischemic flap tissue, and improves flap survival.


METHODS
A randomized, controlled study of 91 adult female Hartley guinea pigs divided into 3 survival groups, 4 neutrophil assay groups, 1 sham group, and 1 control group. Ischemia of varying duration and reperfusion was induced in island flank skin flaps. The treated groups received zileuton, a 5-LO inhibitor, orally during flap ischemia. After reperfusion, systemic neutrophil receptor expression, neutrophil infiltration, and flap survival were measured. Surface receptor molecules on neutrophils from whole blood samples obtained via transcardiac puncture were analyzed using monoclonal antibodies and cell-associated fluorescence. Neutrophil infiltration into a distal 1 cm2 of flap tissue was assessed using myeloperoxidase antibodies. Flap survival was determined within 7 days of surgery.


RESULTS
Untreated flaps with 10 hours of ischemia underwent total necrosis. Treated 2- and 10-hour ischemic flaps survived intact. A significant main effect of the drug treatment was detected using analysis of variance (P<.001). Neutrophil receptor detection in the untreated groups undergoing 2 and 10 hours of ischemia was significantly increased compared with that in the treated groups with the same ischemia times. Skin neutrophil infiltration was significantly decreased in the treated groups.


CONCLUSIONS
Systemic administration of a 5-LO inhibitor is effective in reducing ischemia-reperfusion injury in flap tissue. Our data indicate that there is a significant reduction in neutrophil receptor expression with administration of 5-LO, reducing the priming of systemic neutrophils from circulating cytokines.
Dolan
R
R
Department of Otolaryngology-Head and Neck Surgery, Boston University School of Medicine, Mass, USA.
Hartshorn
K
K
Andry
C
C
Tablante
J
J
Grillone
G
G
McAvoy
D
D
Suntra
C
C
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D018821:CD18 Antigens; D016859:Lipoxygenase Inhibitors; D011956:Receptors, Cell Surface; C063449:zileuton; D006918:Hydroxyurea