Pulmonary dysfunction secondary to soft-tissue endotoxin.
Our purpose was to determine whether peripheral soft tissues produce and release prostanoids in response to local sepsis, and whether this mediator release can produce pulmonary dysfunction. Escherichia coli endotoxin (2 micrograms/kg in 100 mL of saline) was injected below the hide of the flank in seven unanesthetized sheep. In three additional sheep, ibuprofen (12.5 mg/kg of body weight) was injected with the endotoxin. Thromboxane B2 and 6-keto-PGF1 alpha (prostacyclin) levels were measured in tissue lymph draining the flank, lung lymph, pulmonary artery (Ppa), and aortic plasma. One hour after endotoxin administration, mean PaO2 decreased from 90 to 74 mm Hg and Ppa increased from 22 to 35 mm Hg. Lung lymph flow (QL) increased only 50% with QL being protein poor. No increase in lung or peripheral soft-tissue vascular permeability was noted. Tissue lymph (TxB2) increased from 220 +/- 114 to greater than 10,000 pg/mL with levels in Ppa plasma increasing from 300 +/- 128 to 595 +/- 124 pg/mL and aortic plasma from 270 +/- 141 to 410 +/- 104 pg/mL. Lung lymph TxB2 paralleled aortic values. Peak levels of 6-keto-PGF1 alpha in systemic lymph exceeded 2,000 pg/mL while levels in lung lymph remained relatively constant. The pulmonary injury and the increase in TxB2 was prevented by ibuprofen. We conclude that the response of soft tissue to local endotoxin is to release thromboxane in quantities sufficient to raise plasma levels and to produce hypoxia and pulmonary hypertension. The lung dysfunction is not produced by an increase in lung water or vascular permeability.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006976:Hypertension, Pulmonary / Q000209:etiology; D000860:Hypoxia / Q000209:etiology; D007052:Ibuprofen / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008196:Lymph / Q000032:analysis* / Q000503:physiopathology; D008208:Lymphatic System / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D012756:Sheep; D013929:Thromboxane B2 / Q000032:analysis
D004731:Endotoxins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007052:Ibuprofen