Increased lung vascular permeability after pancreatitis and trypsin infusion.
We examined the role of proteases in mediating lung vascular injury after acute hemorrhagic pancreatitis. Studies were made in sheep in which pulmonary lymph was collected for assessment of the changes in transvascular fluid and protein exchange. The induction of pancreatitis by injection of trypsin and sodium taurocholate into the pancreas resulted in increases in pulmonary lymph flow and transvascular protein clearance (lymph flow x lymph-to-plasma protein concentration ratio). The pulmonary vascular pressures did not change significantly after pancreatitis, indicating that the increases in pulmonary lymph flow and protein clearance were due to increased pulmonary endothelial permeability. The response to pancreatitis was also characterized by decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was a common morphologic feature in this group. In another group, an intravenous infusion of trypsin, which produced decreases in antiprotease activity comparable to those observed after pancreatitis, also resulted in increases in pulmonary lymph flow and transvascular protein clearance. These increases in lymph fluxes were comparable to those observed after pancreatitis and were also associated with decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was evident in this group upon histologic examination. In a third group, pretreatment with Trasylol prevented the increases in pulmonary lymph flow and transvascular protein clearance after pancreatitis, suggesting that the pancreatitis-induced pulmonary vascular injury is the result of the release of proteases. The results indicate a common pulmonary vascular response to acute pancreatitis and trypsin infusion. The release of proteases into the circulation after acute pancreatitis may be the initiating event mediating the pulmonary vascular injury.
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002199:Capillary Permeability; D007263:Infusions, Parenteral; D008168:Lung / Q000503:physiopathology*; D010195:Pancreatitis / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D014357:Trypsin / Q000008:administration & dosage*
D007611:Aprotinin; D014357:Trypsin