Dimethylthiourea does not ameliorate reperfusion lung injury in dogs or rabbits.
We previously demonstrated that in vivo reperfusion of a dog lung after 48 h of pulmonary arterial (PA) ischemia results in pulmonary edema with a significant infiltrate of polymorphonuclear leukocytes. We hypothesized that the injury resulted from production of hydroxyl radical by activated neutrophils. In the current study, we attempted to prevent the injury in both dogs and rabbits with dimethylthiourea (DMTU), a scavenger of hydroxyl radical. After 48 h of left PA occlusion in 18 dogs, DMTU was administered to 9 animals and 9 were not treated. The occlusion was then released, and the dogs were killed 4 h later. Reperfusion resulted in a drop in leukocyte count and left lung edema, but there was no difference between treated and untreated animals. The wet-to-dry ratios of the lungs in the treated group were 5.76 +/- 0.44 (SE) on the reperfused left side and 4.50 +/- 0.06 (P less than 0.05) on the right side. In the untreated groups the comparable ratios were 5.73 +/- 0.31 and 4.92 +/- 0.10 (P less than 0.05 for right vs. left). Histological examination revealed significant differences between the right and left lungs in the extent of intra-alveolar granulocytes and macrophages but did not reveal differences between the treated and untreated animals. To ensure that neither the model nor the lack of response to DMTU was species specific, we then developed a rabbit model of reperfusion edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Bishop
M J
MJ
Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195.
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Cheney
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D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006878:Hydroxides; D017665:Hydroxyl Radical; D007511:Ischemia / Q000150:complications; D007970:Leukopenia / Q000209:etiology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D055370:Lung Injury; D008264:Macrophages / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D011817:Rabbits; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D006878:Hydroxides; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D013890:Thiourea