Comparison of alpha- and gamma-thrombin on lung fluid balance in anesthetized sheep.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000768:Anesthesia, General; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000378:metabolism*; D006706:Homeostasis; D008168:Lung / Q000378:metabolism*; D012756:Sheep; D013917:Thrombin / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005337:Fibrin; D013917:Thrombin