Ischemia reperfusion injury in the rabbit ear is reduced by both immediate and delayed CD18 leukocyte adherence blockade.
mAb blockade of CD18-mediated neutrophil adherence has previously been shown to reduce tissue injury in the rabbit ear as a result of ischemia followed by reperfusion. Similar injury reduction has been demonstrated whether treatment is given before ischemia or at the time of reperfusion. We examined the effects of delayed treatment with blocking CD18 mAb (60.3) after reperfusion of ischemic rabbit ears. The central neurovascular bundle of rabbit ears was isolated by microsurgery, the remainder of the ear devascularized, and all nerves cut to render the ear anesthetic. Arterial blood flow was occluded with a microvascular clamp for 6 h at an ambient temperature of 23 to 24 degrees C. The clamp was then removed and the ear allowed to reperfuse. Rabbits were divided into five treatment groups: 1) i.v. saline at reperfusion, 2) i.v. mAb 60.3 (2 mg/kg) at reperfusion, 3) i.v. mAb 60.3 1 h after reperfusion, 4) i.v. mAb 60.3 4 h after reperfusion, and 5) i.v. mAb 60.3 12 h after reperfusion. Ear edema (measured by volume displacement) was determined daily for 7 days. Edema in the immediate, 1 h, and 4 h mAb-treated groups was significantly less than in saline-treated controls, although less pronounced in the 4-h treatment group. Tissue necrosis measured at 7 days was significantly reduced in the same three mAb-treated groups compared with controls. However, edema and tissue necrosis in the 12 h mAb-treated group were similar to controls. We conclude that mAb blockade of CD18 at 1 h after reperfusion is as effective as immediate treatment in reducing ischemia reperfusion injury in the rabbit ear. Delaying treatment for 4 h is also effective but less so, whereas delaying treatment for 12 h results in no beneficial effects.
Sharar
S R
SR
Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195.
Mihelcic
D D
DD
Han
K T
KT
Harlan
J M
JM
Winn
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D004431:Ear, External / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology*; D009336:Necrosis; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens