Increased transvascular protein transport in lungs induced by nonthrombogenic gamma-thrombin

Infusion of 1.2 nmol/kg body wt of alpha-thrombin (2.6 clotting U/micrograms) or 12 nmol/kg of gamma-thrombin (less than 0.005 U/microgram) into the pulmonary artery of halothane-anesthetized sheep produced two-to threefold increases in mean pulmonary arterial pressure (Ppa), mean pulmonary arterial wedge pressure (Ppw), and pulmonary vascular resistance (PVR). Pulmonary lymph flow (Qlym) also increased two- to threefold without significant changes in the lymph-to-plasma protein concentration ratio (L/P). Leukocyte counts decreased 75% in both groups and rebounded in the gamma-thrombin group but remained depressed in the alpha-thrombin group. Platelet counts decreased 30 and 85% in alpha- and gamma-thrombin groups, respectively, and remained low at 4 h postinfusion in both groups. Plasma fibrinogen concentrations decreased similarly within 15 min after thrombin infusion in both groups, and concentrations of fibrin(ogen) degradation products (FDP) increased similarly. Fibrin was present in pulmonary vessels after alpha-thrombin challenge but not after gamma-thrombin challenge. In contrast, infusion of 1.2 nmol/kg of gamma-thrombin (matching the alpha-thrombin dosage) produced no significant increases in Ppa, Ppw, PVR, Qlym or in the leukocyte and platelet counts. These data demonstrate that high concentrations of the nonthrombogenic gamma-thrombin increase lung transvascular protein transport independent of intravascular clotting in the lung.