AJP - Heart and Circulatory Physiology, Vol 256, Issue 6 1690-H1696, Copyright © 1989 by American Physiological Society
Increased transvascular protein transport in lungs induced by nonthrombogenic gamma-thrombin
R. R. Garcia-Szabo, J. W. Fenton 2nd, S. K. Lo, M. Hussain and A. B. Malik
Department of Physiology, Albany Medical College of Union University, New York.
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.
