BIOCHEMICAL AND MORPHOLOGICAL ALTERATIONS IN XYLAZINE-INDUCED PULMONARY-EDEMA

Sprague-Dawley rats were given 42 mg/kg xylazine intramuscularly, and lungs were lavaged with phosphate-buffered saline 3, 6, and 12 hr late r. 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-tre ated 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 giv en 42 mg/kg xylazine intramuscularly, and lungs were fixed 0.5 and 12 hr later. Histologically, severe pulmonary edema (PE) involving the al veoli and perivascular stroma was observed. Fibrin, increased numbers of eosinophils, and macrophages with foamy cytoplasm were present in t he alveoli of all treated animals. Ultrastructurally, endothelial dama ge, characterized by thinning, detachment from basement membranes, or bleb formation, was observed. The lesions were similar in both xylazin e groups, differing mainly in severity with the 12-hr group having mor e severe lesions than the 0.5-hr group. To determine whether endotheli al injury is caused by direct toxicity of xylazine, bovine pulmonary a rtery endothelial cells (BPAECs) were incubated with xylazine (0.3, 3, and 30 mug) for 0.5 or 3 hr. Xylazine did not have any effects on BPA ECs, as indicated by phase-contrast microscopy and dye-exclusion viabi lity 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 o xygen radicals and TNF are possibly involved, IL-1 does not appear to play a role in xylazine-induced PE.