Pulmonary hemodynamic effects of antisheep serum-induced leukopenia

Antisheep antileukocyte serum (ALS) was produced in rabbits, purified, and adsorbed against erythrocytes and platelets. The ALS was infused intra-arterially over a 3-hour period into anesthetized sheep (n = 6) prepared with lung lymph fistulas. Pulmonary vascular resistance (PVR) and pulmonary lymph flow (Qlym) increased two- to threefold while the lymph-to-plasma protein concentration ratio (L/P) did not change from baseline, suggesting an increase in pulmonary vascular permeability to proteins. The arterial leukocyte count decreased from 4,935 +/- 840 to 1,385 +/- 325 cells/microliters, the neutrophil count decreased from 1,045 +/- 265 to 340 +/- 130 cells/microliters, and the platelet count decreased from 2.8 X 10(5) +/- 0.2 X 10(5) to 0.65 X 10(5) +/- 0.12 X 10(5) cells/microliters. ALS induced neutrophil aggregation in vitro, but not platelet aggregation. In the present study, we also examined the effects of ALS-induced leukopenia on the increase in pulmonary vascular permeability after intravenous alpha-thrombin challenge to assess the role of leukocytes in mediating the increased permeability response. Sheep (n = 5) were made leukopenic by an intramuscular injection of ALS; Qlym was in the normal range 4 to 5 hours after the ALS administration. In the leukopenic group, thrombin challenge caused an increase in Qlym from 7.8 +/- 0.7 to 12.9 +/- 1.9 ml/hr (a 64% increase) while L/P decreased from 0.86 +/- 0.04 to 0.70 +/- 0.05 (a 19% decrease). In contrast, thrombin-induced intravascular coagulation in control sheep (n = 5) produced a 250% increase in Qlym with an increase in L/P. The results indicate that leukocytes are required for the increase in lung vascular permeability after thrombin-induced intravascular coagulation.