CVF-induced decomplementation: effect on lung transvascular protein flux after thrombin.
We examined the effects of cobra venom factor (CVF) on the changes in pulmonary hemodynamics and transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in unanesthetized sheep prepared with lung lymph fistulas. The animals received tranexamic acid (100 mg) to suppress fibrinolysis and were then challenged with an intravenous infusion of alpha-thrombin (80 U/kg). Control-thrombin challenged sheep were compared with the CVF-treated sheep challenged with the same thrombin dosage. CVF treatment (187 U X kg-1 X day-1 for 4 days) decreased the total hemolytic complement activity by 45% of control. Thrombin infusion in control sheep increased the mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and lymph protein clearance (pulmonary lymph flow X lymph-to-plasma protein concentration ratio, Clym). Thrombin infusion in CVF-treated sheep produced smaller increments in Ppa, PVR, and Clym. Pulmonary lymph obtained from control-thrombin and CVF-thrombin sheep induced migration of granulocytes obtained from normal unchallenged sheep. The granulocytes obtained from CVF-treated sheep responded relatively less to the migratory and O-2-generating stimuli (i.e., zymosan-treated serum, pulmonary lymph from sheep after thrombin challenge, and plasma from sheep after CVF treatment) compared with normal granulocytes. The attenuation of the thrombin-induced increases in Ppa, PVR, and lung transvascular fluid and protein exchange by CVF treatment may be the result of impaired function of granulocytes.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects*; D004546:Elapid Venoms / Q000494:pharmacology*; D006098:Granulocytes / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006461:Hemolysis; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013481:Superoxides / Q000097:blood; D013917:Thrombin / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D004546:Elapid Venoms; D011506:Proteins; C016310:cobra venom factor; D013481:Superoxides; D013917:Thrombin