Endotoxin-induced prostanoid production by the burn wound can cause distant lung dysfunction.
We injected Escherichia coli endotoxin, 2 micrograms/kg, beneath the eschar of sheep with 25% total body surface full-thickness burns to determine whether burn tissue in the presence of endotoxin releases prostanoids, particularly thromboxane A2, (TxA2), and if increased local TxA2 production can lead to distant lung dysfunction. We compared this response to the lung injury produced by the same dose given intravenously. We noted a marked increase in burn tissue TxA2 production after subeschar endotoxin as reflected in significant increases in burn lymph and pulmonary artery TxB2 levels. Pulmonary artery pressure increased from 22 to 38 mm Hg and PaO2 decreased from 89 to 71 torr while lung lymph flow (QL) increased only modestly with no evidence of increased lung permeability. The TxA2 production and the lung response were prevented by the subeschar injection of ibuprofen, 12.5 mg/kg. Circulating endotoxin was noted in only one of five sheep. After intravenous (endotoxin), a significant increase in lung TxA2 production was noted and a characteristic two-phase lung injury was seen with an initial phase basically identical to that seen with the subeschar injection followed by an increase in lung protein permeability. Burn tissue endotoxin can stimulate local TxA2 production leading to distant lung dysfunction without the need for circulating endotoxin. The source of the TxA2 is the burn, while with endotoxemia the source is the lung.
D000818:Animals; D002056:Burns / Q000150:complications* / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage*; D006439:Hemodynamics; D007052:Ibuprofen / Q000502:physiology; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000209:etiology*; D008196:Lymph / Q000032:analysis; D011651:Pulmonary Artery / Q000032:analysis; D012756:Sheep; D013928:Thromboxane A2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis*; D013997:Time Factors
D004731:Endotoxins; D013931:Thromboxanes; D013928:Thromboxane A2; D007052:Ibuprofen