Thrombin-induced lung vascular injury. Roles of fibrinogen and fibrinolysis.
We examined the contributions of fibrin and the fibrinolytic mechanism in mediating the thrombin-induced lung vascular injury. Studies were made in sheep in which alterations in lung transvascular fluid and protein exchange were assessed using the lung lymph fistula preparation. Group I(n = 10) control sheep in which left atrial pressure was raised to increase pulmonary lymph flow (Qlym); Group II(n = 8) control sheep in which thrombin was infused intravenously (58.3 +/- 12.6 U/kg) to induce pulmonary thromboembolization; Group III (n = 6) sheep were defibrinogenerated using Ancrod (purified fraction of venom of Agkistrodon rhodostoma) prior to embolization with thrombin (124.5 +/- 2.5 U/kg); Group IV (n = 13) sheep were treated with tranexamic acid to inhibit fibrinolysis prior to embolization with thrombin (140.0 +/- 25.8 U/kg). In Group II, pulmonary thromboembolization increased Qlym without a change in the steady-state lymph-to-plasma protein concentration ratio (L/P). Raising left atrial pressure (increases Pla) postembolization to test for an increase in pulmonary vascular permeability to proteins further increased Qlym but did not alter L/P, indicating an increase in permeability. In Group III, the thrombin-induced increase in Qlym was blunted and the L/P decreased; increases Pla further increased Qlym but decreased L/P. In Group IV, Qlym also increased after thrombin-induced embolization and L/P decreased; increases Pla further increased Qlym but decreased L/P. The responses to increases Pla of Groups III and IV were similar to the response of Group I rather than to that of Group II, indicating that defibrinogenation and fibrinolytic inhibition prevented the increase in lung vascular permeability. The results indicate that circulating fibrinogen and activation of plasmin are necessary for development of lung vascular injury after pulmonary thromboembolization.
D000818:Animals; D005340:Fibrinogen / Q000502:physiology*; D005342:Fibrinolysis / Q000187:drug effects; D008168:Lung / Q000098:blood supply*; D008196:Lymph / Q000502:physiology; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000209:etiology* / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure; D012756:Sheep; D013917:Thrombin / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D005340:Fibrinogen; D013917:Thrombin