Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock.
Recent studies suggest that neutrophils are an important factor in the organ injury associated with ischemia and shock. Increased neutrophil-endothelial adhesiveness is essential for neutrophil-mediated vascular injury. To examine the role of neutrophils and neutrophil adhesiveness in the development of injury after hypovolemic shock, and to determine whether this injury is a consequence of reperfusion, we used the monoclonal antibody (MAb) 60.3 (directed to the primary human neutrophil adherence glycoprotein, CD18) to block neutrophil adherence functions at the time of resuscitation in a rabbit model of hemorrhagic shock. None of the unanesthetized control animals subjected to 2 hours of shock (cardiac output, 30% of baseline) followed by resuscitation survived 5 days. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 71% of the animals that received MAb 60.3 immediately before resuscitation survived 5 days (p less than 0.005), and visceral organ injury was absent or markedly attenuated. We conclude that a significant proportion of injury resulting from shock and resuscitation occurs after the ischemic insult and that increased neutrophil adhesiveness plays an important role in the development of multiple organ injury and death following shock and resuscitation (in this model). This injury may be significantly reduced by blocking neutrophil adherence functions with the MAb 60.3--even if administration is delayed until resuscitation.
Vedder
N B
NB
Department of Surgery, University of Washington, Seattle.
Fouty
B W
BW
Winn
R K
RK
Harlan
J M
JM
Rice
C L
CL
D000138:Acidosis / Q000209:etiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D005260:Female; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*
D000911:Antibodies, Monoclonal