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 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 micrograms) 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.
Amouzadeh
H R
HR
Department of Physiological Sciences, Oklahoma State University, Stillwater 74078-0353.
Qualls
C W
CW
Wyckoff
J H
JH
Dzata
G K
GK
Sangiah
S
S
Mauromoustakos
A
A
Stein
L E
LE
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D014991:Xylazine / Q000633:toxicity*
D007375:Interleukin-1; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D014991:Xylazine; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase