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Biochemical and Morphological Alterations in Xylazine-Induced Pulmonary Edema*,

Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-0353

Charles W. Qualls, Jr

Department of Veterinary Pathology, Oklahoma State University, Stillwater, Oklahoma 74078-0353

John H. Wyckoff, III

Department of Parasitology, Microbiology and Public Health, Oklahoma State University, Stillwater, Oklahoma 74078-0353

Gladstone K. Dzata

Department of Parasitology, Microbiology and Public Health, Oklahoma State University, Stillwater, Oklahoma 74078-0353

Subbiah Sangiah

Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-0353

Andy Mauromoustakos

Agricultural Statistics Laboratory, University of Arkansas, Fayetteville, Arkansas 72701

Larry E. Stein

Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-0353

Sprague-Dawley rats were given 42 mg/kg xylazine intramuscularly, and lungs were lavaged with phosphate-buffered saline 3, 6, and 12 hr later. Total protein, lactate dehydrogenase (LDH), xanthine oxidase (XO), tumor necrosis factor (TNF), and interleukin 1 (IL-1) were measured in bronchoalveolar lavage fluid (BALF). Protein concentration, LDH, XO, and TNF levels were increased (p < 0.05) in the BALF from xylazine-treated rats as compared to controls. IL-1 level was unchanged at 3 and 6 hr and was reduced (p < 0.05) at 12 hr. Another group of rats was given 42 mg/kg xylazine intramuscularly, and lungs were fixed 0.5 and 12 hr later. Histologically, severe pulmonary edema (PE) involving the alveoli and perivascular stroma was observed. Fibrin, increased numbers of eosinophils, and macrophages with foamy cytoplasm were present in the alveoli of all treated animals. Ultrastructurally, endothelial damage, characterized by thinning, detachment from basement membranes, or bleb formation, was observed. The lesions were similar in both xylazine groups, differing mainly in severity with the 12-hr group having more severe lesions than the 0.5-hr group. To determine whether endothelial injury is caused by direct toxicity of xylazine, bovine pulmonary artery endothelial cells (BPAECs) were incubated with xylazine (0.3, 3, and 30 µg) for 0.5 or 3 hr. Xylazine did not have any effects on BPAECs, as indicated by phase-contrast microscopy and dye-exclusion viability assay. These results indicate that xylazine-induced PE is due to increased permeability resulting from endothelial injury, which is not caused by direct effect of xylazine on pulmonary endothelium. While oxygen radicals and TNF are possibly involved, IL-1 does not appear to play a role in xylazine-induced PE.

Key Words: Acute lung injury • endothelium • xanthine oxidase • oxygen radicals • tumor necrosis factor • interleukin 1

Toxicologic Pathology, Vol. 21, No. 6, 562-571 (1993)
DOI: 10.1177/019262339302100607


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