Inhibition of neutrophil adhesion does not prevent ischemic spinal cord injury.
Paraplegia may occur after transient aortic occlusion as a consequence of primary ischemia to the spinal cord or injury during the reperfusion period. In animal models of ischemia/reperfusion there is evidence that reperfusion injury may be modulated partially by neutrophils. The efficacy of the neutrophil adherence blocking murine monoclonal antibody (MAb 60.3) was assessed in spinal cord ischemia/reperfusion in rabbits. Spinal cord ischemia was accomplished by balloon catheter occlusion of the infrarenal aorta. Neurologic assessment was graded as normal, partial neurologic deficit, or complete paralysis. Electrophysiologic monitoring with somatosensory evoked potentials was used to determine the optimal length of time of occlusion. Animals were treated randomly with 2 mg/kg of intravenous Mab 60.3 (n = 8) or saline solution (n = 9) with the investigator unaware of treatment. Mean occlusion times were no different between groups (control, 32.7 +/- 3.6 minutes versus MAb, 32.4 +/- 6.0 minutes). Five (55%) saline-treated and four (50%) MAb 60.3-treated animals became paraplegic. Animals with initial paraparesis all progressed to flaccid paraplegia within 24 hours. We conclude that spinal cord injury after transient aortic occlusion is independent of the CD11/CD18 glycoprotein complex of the neutrophil. Injury in this setting may occur during ischemia and thus may not be dependent on neutrophils or reperfusion.
Forbes
A D
AD
Division of Cardiothoracic Surgery, University of Washington, Seattle 98195.
Slimp
J C
JC
Winn
R K
RK
Verrier
E D
ED
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010264:Paraplegia / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D013116:Spinal Cord / Q000098:blood supply*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion