EFFECTS OF PLASMA KALLIKREIN SPECIFIC INHIBITOR AND ACTIVE-SITE BLOCKED FACTOR VIIA ON THE PULMONARY VASCULAR INJURY-INDUCED BY ENDOTOXIN IN RATS

The acute respiratory distress syndrome (ARDS) is a serious complicati on of sepsis. To evaluate the role of the coagulation system in the pa thogenesis of ARDS in sepsis, we examined the effects of the administr ation of a synthetic plasma kallikrein specific inhibitor (PKSI) and o f active-site blocked factor Wa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PK SI prevented the pulmonary vascular injury induced by ET as well as pu lmonary histological changes in animals administered ET, but it did no t affect the intravascular coagulation. The opposite effect was seen w ith DEGR-VIIa, which prevented the intravascular coagulation but nor. the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutr ophils. Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neu trophils. The intrinsic pathway of coagulation may be more important t han the extrinsic pathway in the pulmonary vascular injury produced by ET.