title: Activated protein C attenuates cardiopulmonary bypass-induced acute lung injury through the regulation of neutrophil activation.
abstract: OBJECTIVE
  Cardiopulmonary 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.
  
  
  METHODS
  Rats 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Administration 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.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Syunji
authors.initials: S
authors.lastname: Inamori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Michiharu
authors.initials: M
authors.lastname: Suga
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D011486:Protein C / Q000008:administration & dosage*; D011654:Pulmonary Edema / Q000276:immunology / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011486:Protein C