NEUTROPHIL SEQUESTRATION AND PULMONARY DYSFUNCTION IN A CANINE MODEL OF OPEN-HEART-SURGERY WITH CARDIOPULMONARY BYPASS - EVIDENCE FOR A CD18-DEPENDENT MECHANISM

Background Previous studies documented an inflammatory reaction to cardiopulmonary bypass with neutrophil (PMN) sequestration in the lungs, contributing to microvascular injury and postoperative pulmonary dysfunction. This study explored the hypothesis that the beta(2) integrin CD18, a leukocyte adhesion molecule, mediates this response. Methods and Results Fifteen adult, mixed-breed dogs underwent 90 minutes of cardiopulmonary bypass with 3 hours of subsequent recovery. Seven additional dogs were treated before cardiopulmonary bypass with a 1-mg/kg IV bolus of R15.7 IgG, a monoclonal antibody to CD18. Both groups were compared with 5 sham bypass control dogs. Bypassed dogs demonstrated an increased number of PMNs sequestered in the lungs 3 hours after bypass compared with sham bypass control dogs (1466+/-75 versus 516+/-43 PMN/mm(2) alveolar surface area, mean+/-SEM, P<.001). Also, when PMNs from bypass dogs were compared with those from sham dogs, they produced more H2O2 (305+/-45 versus 144+/-48 amol H2O2 per phagocyte per 20 minutes, P<.05). Bypass dogs had significantly decreased arterial oxygenation 3 hours after the proce dure compared with shams (457+/-20 versus 246+/-49 mm Hg, P<.05), and they had a significantly increased lung wet-to-dry weight ratio (5.38+/-0.14 versus 4.54+/-0.15, P=.003), demonstrating a significant increase in lung water. R15.7 markedly attenuated pulmonary PMN accumulation in bypass dogs (412+/-73 PMN/mm(2), P<.001) and significantly inhibited PMN production of H2O2 (146+/-18 amol H2O2 per phagocyte per 20 minutes, P<.05) Bypass dogs pretreated with R15.7 also had improved oxygenation (445+/-28 mm Hg, P<.05) and tended to have less lung water accumulation after bypass (4.99+/-0.20). Conclusions Pulmonary dysfunction after cardiopulmonary bypass is caused, at least in part, by a neutrophil-mediated, CD18-dependent mechanism.