Acute pulmonary hypertension and lung thromboxane release after endotoxin infusion in normal and leukopenic sheep.

We compared alterations of pulmonary hemodynamics with the plasma concentrations of thromboxane B2, 6-keto-PGF la , and PGF20 following intravenous Escherichia coli endotoxin infusion (1 /ig/kg) in three groups of awake sheep.Group 1 served as controls.The animals in group 2 were rendered leukopenic (<1000 WBC/mm 3 ) by nitrogen mustard treatment.Group 3 received ibuprofen (12 mg/kg) one hour before endotoxin.After endotoxin infusion, the pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) increased markedly in groups 1 and 2; however, in group 2, the increases of PAP and PVR were half those of group 1.In group 3, only minimal increases of PAP and PVR were measured.In groups 1 and 2, the rise of PAP correlated with an increased plasma TxB2 concentration at 30 minutes after endotoxin (group 1-from 0.5 ± 0.04 to 16 ± 3 ng/ml; group 2-from 0.32 ± 0.1 to 5.6 ± 1.2 ng/ml).The peak plasma concentrations of TXB2 were significantly less in group 2 than in group 1.In the sheep in both groups 1 and 2, 20 minutes after endotoxin infusion, consistent pulmonary artery to aortic increases of TxB2 were measured (group 1 A3.7 ± 1.1 ng/ml and group 2 A3.1 ± 0.7 ng/ml).In group 3, plasma TxB2 increased slightly to 240 ± 80 pg/ml.Plasma concentrations of 6-keto-PGFi,, increased in group 1 from 0.06 ± 0.01 to 0.59 ± 0.12 ng/ml and in group 2 from 0.06 ± 0.01 to 0.58 ± 0.12 ng/ml.In group 3 sheep, plasma concentrations of 6-keto-PGF ]o remained below the detection limit of the radioimmunoassay.TxA2 is a likely mediator of endotoxin-induced pulmonary hypertension and is generated in large quantities by cells in the lung.Circulating leukocytes contribute substantially to the peak plasma concentrations of thromboxane following endotoxin infusion.(Circ Res 50: [688][689][690][691][692][693][694] 1982)