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Ischemia reperfusion injury in the rabbit ear is reduced by both immediate and delayed CD18 leukocyte adherence
S R Sharar1, D D Mihelcic, K T Han
1Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195.
Abstract:
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.
Insights
Blocking CD18 monoclonal antibody (mAb) effectively reduces ischemia reperfusion injury in rabbit ears. Treatment up to 4 hours after reperfusion shows significant benefits, but delaying for 12 hours offers no advantage.
Area of Science:
- Immunology
- Vascular Surgery
- Biomedical Engineering
Background:
- Ischemia reperfusion (I/R) injury is a significant clinical challenge.
- CD18-mediated neutrophil adherence contributes to I/R tissue damage.
- Previous studies show efficacy of CD18 mAb blockade before or at reperfusion.
Purpose of the Study:
- To evaluate the efficacy of delayed treatment with CD18 blocking monoclonal antibody (mAb) 60.3 after reperfusion in a rabbit ear ischemia-reperfusion model.
- To determine the optimal time window for administering CD18 mAb therapy to mitigate I/R injury.
Main Methods:
- Rabbit ears underwent 6-hour arterial occlusion followed by reperfusion.
- Five treatment groups received either saline or CD18 mAb (60.3) at varying times: immediately, 1, 4, or 12 hours post-reperfusion.
- Ear edema and tissue necrosis were assessed over 7 days.
Main Results:
- Treatment with CD18 mAb at reperfusion, 1 hour, and 4 hours post-reperfusion significantly reduced ear edema and tissue necrosis compared to saline controls.
- The 4-hour treatment group showed less pronounced but still significant benefits.
- Treatment delayed by 12 hours post-reperfusion did not provide any significant beneficial effects.
Conclusions:
- CD18 mAb blockade is effective in reducing ischemia reperfusion injury in rabbit ears.
- Therapeutic benefit is observed when treatment is administered up to 4 hours after reperfusion, with 1-hour post-reperfusion treatment being as effective as immediate administration.
- Delayed treatment beyond 4 hours, specifically at 12 hours, is ineffective in mitigating I/R injury.