Effect of hydroxyl radical scavenging on endotoxin-induced lung injury.
The release of oxygen radicals, in particular the hydroxyl radical, from sequestered neutrophils produces acute lung injury after a number of insults. Our purpose was to determine whether hydroxyl radical, OH., is responsible for the lung injury from endotoxin characterized by (1) pulmonary leukostasis, (2) increased thromboxane production leading to pulmonary hypertension and hypoxia, and (3) increased protein permeability. This hypothesis was tested by infusion of a selective OH. scavenger, dimethyl thiourea (0.75 gm/kg), into unanesthetized sheep before endotoxin and comparison of the response to that seen with endotoxin alone. Pulmonary vascular integrity was measured by the use of lung lymph flow, QL, and lymph protein transport. Thromboxane A2 was measured as TxB2 and prostacyclin as 6-keto-PGF1 alpha. We found no difference in the degree of leukopenia and hypoxia after endotoxin or the levels of TxB2, 6-keto-PGF1 alpha, and pulmonary hypertension with dimethyl thiourea, compared with endotoxin alone. The permeability injury was also identical, with a twofold to threefold increase in protein-rich lymph seen in both groups. It appears that OH. does not play a major causative role in either phase of endotoxin lung injury.
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008196:Lymph / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012756:Sheep; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D004731:Endotoxins; D005609:Free Radicals; D006878:Hydroxides; D011506:Proteins; D017665:Hydroxyl Radical; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C038983:1,3-dimethylthiourea; D013890:Thiourea