Journal of Applied Physiology, Vol 57, Issue 5 1375-1383, Copyright © 1984 by American Physiological Society
Comparison of alpha- and gamma-thrombin on lung fluid balance in anesthetized sheep
R. R. Garcia-Szabo, D. F. Kern, R. Bizios, J. W. Fenton 2nd, F. L. Minnear, S. K. Lo and A. B. Malik
We examined the effects of varying dosages of thrombin on lung fluid
balance in halothane-anesthetized sheep prepared with lung lymph fistulas.
A 15-min iv infusion of sublethal doses of alpha-thrombin (2.5 clotting
units/micrograms), the native enzyme, at 0.6 or 1.1 nmol active enzyme/kg
body wt increased the mean pulmonary arterial pressure (Ppa) and pulmonary
vascular resistance (PVR) two- to threefold. Neither parameter increased in
a dose-dependent manner. Platelet counts decreased 50% with both dosages.
Leukocyte counts decreased 35 and 75% from base line in the low- and
high-dosage groups, respectively, and reached comparable levels of 50%
below base line at 60-min postinfusion in both groups. Plasma fibrinogen
concentrations decreased in a dose-dependent manner preceding
dose-dependent increases in pulmonary lymph flow (Qlym) and lymph protein
clearance (Clym). Fibrin deposition in pulmonary vessels was greater at 30
than at 180 min postinfusion. In contrast, a 15-min iv infusion of
gamma-thrombin (0.002 clotting units/micrograms), which lacks the
fibrinogen recognition site, at 1.2 nmol active enzyme/kg produced no
significant increases in PVR, Ppa, Qlym, or Clym. The fibrinogen
concentration did not change significantly, whereas platelet and leukocyte
counts decreased 25% within 15 min. Fibrin microthrombi were less prominent
in pulmonary vessels. Fibrin deposition associated with intravascular
coagulation may be an important factor mediating thrombin-induced increases
in pulmonary transvascular fluid and protein exchange.
