Activated protein C attenuates cardiopulmonary bypass-induced acute lung injury through the regulation of neutrophil activation

ObjectiveCardiopulmonary bypass is known to induce systemic inflammatory responses that injure multiple organs, especially the lungs. Activated protein C has been demonstrated to play an important role in the regulation of inflammation in addition to coagulation. We investigated the anti-inflammatory effects of activated protein C in a rat model of cardiopulmonary bypass.MethodsRats were randomized to receive an intravenous bolus of vehicle (control), 0.1 mg/kg diisopropyl fluorophosphate-activated protein C, or 0.1 mg/kg activated protein C 10 minutes before the initiation of cardiopulmonary bypass. Rats underwent cardiopulmonary bypass for 60 minutes followed by another 60-minute observation.ResultsThe activated protein C group showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio after cardiopulmonary bypass than the control and diisopropyl fluorophosphate-activated protein C groups. Furthermore, lung pathology revealed minimal inflammatory change in the activated protein C group. A marked increase in CD11b expression and a decrease in CD62L expression after cardiopulmonary bypass were observed in the control and diisopropyl fluorophosphate-activated protein C groups. However, administration of activated protein C significantly attenuated these changes. Lung content of tumor necrosis factor-α and interleukin-1β in the activated protein C group tended to be lower than in the other groups. Lung content of macrophage inflammatory protein-2 in the activated protein C group was significantly lower than in the diisopropyl fluorophosphate-activated protein C group.ConclusionsAdministration of activated protein C before cardiopulmonary bypass attenuates acute lung injury induced by cardiopulmonary bypass at least in part through the inhibition of neutrophil activation and possibly via the attenuation of proinflammatory cytokine production in this rat model of cardiopulmonary bypass.