Nitric oxide inhibits neutrophil adhesion during experimental extracorporeal circulation

Myocardial and pulmonary injuries often occur after cardiopulmonary bypass, mediated in part by neutrophil activation and adhesion to endothelial cells. The effects of nitric oxide (NO) administration on neutrophil adhesion to endothelial cells after simulated extracorporeal circulation were investigated.

Two identical extracorporeal circulation circuits were primed with fresh human blood and circulated for 2 h at 37 degrees C. Nitric oxide at a 40-ppm concentration was added to one of the oxygenators in each pair. Neutrophil CD11b/CD18 expression and their adhesion to human umbilical vein endothelial cell monolayers were assayed in leukocytes isolated from samples drawn from the circuit 30, 60, 90, and 120 min after circulation began. In another series of experiments, blocking monoclonal antibodies to both neutrophil CD11b and CD18 were incubated with polymorphonuclear leukocytes after removal from the circuit before the adhesion assay.

After 60 min of circulation, the neutrophils from NO-treated circuits showed significantly reduced CD11b/CD18 surface expression compared with the control group. There was also a significant reduction in neutrophil-endothelial adhesion in the NO group after 120 min of circulation. Monoclonal antibodies to both CD11b and CD18 significantly inhibited the adhesion of polymorphonuclear leukocytes at endothelial cells after 120 min of circulation.

These results confirm that neutrophil activation occurs during cardiopulmonary bypass. The addition of NO to the circuits of extracorporeal circulation significantly affects neutrophil adhesion to endothelial cells.