Xylazine-induced pulmonary edema in rats.
Inhibitors of cytochrome P450, such as SK&F 525-A, prolong the duration of xylazine-ketamine anesthesia and cause pulmonary edema (PE) and death in rats. To determine the cause of PE, Sprague-Dawley rats were given a single dose of xylazine (21 mg/kg, im) alone or in combination with ketamine (45 mg/kg, im) and/or SK&F 525-A (50 mg/kg, ip) and percentage lung to body weight (%LW/BW) ratios (as an indicator of PE) were compared. The results indicated that xylazine caused PE which was independent of ketamine and was enhanced by SK&F 525-A. Subsequently, it was determined that 42 mg/kg xylazine, im, is an optimal edemagenic dose. Xylazine (42 mg/kg, im) increased the %LW/BW ratio as compared to control. Pleural effusion (PLE) of various amounts was observed in 75% of the animals. The pleural fluid to serum protein ratio for xylazine was similar to that obtained for alpha-naphthylthiourea (5 mg/kg, ip). Extensive serous PLE and alveolar edema with hemorrhage were found at necropsy in xylazine-treated rats. Pretreatment with yohimbine (4.2 mg/kg), prazosin (20 mg/kg), tolazoline (20 mg/kg), yohimbine (4.2 mg/kg) plus prazosin (20 mg/kg), atropine (20 mg/kg), dimethyl sulfoxide (DMSO) (7.8 g/kg), allopurinol (50 mg/kg), superoxide dismutase (20,000 U/kg), catalase (20,000 U/kg), BW755C (50 mg/kg), ibuprofen (50 mg/kg), cystathionine (100 mg/kg) plus taurine (100 mg/kg) did not affect the %LW/BW ratio. PLE was increased by yohimbine, yohimbine plus prazosin, and allopurinol, reduced by DMSO, and not changed in other groups. The results indicate that xylazine caused increased-permeability PE characterized by rapid onset, cellular damage and protein-rich pleural fluid. PE may not be mediated by adverse cardiovascular effects of xylazine and oxygen radicals are possibly involved in its etiology.
Amouzadeh
H R
HR
Department of Physiological Sciences, Oklahoma State University, Stillwater 74078.
Sangiah
S
S
Qualls
C W
CW
Cowell
R L
RL
Mauromoustakos
A
A
D000777:Anesthetics; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010994:Pleura / Q000737:chemistry / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000031:analogs & derivatives / Q000633:toxicity; D014991:Xylazine / Q000633:toxicity*
D000777:Anesthetics; D001798:Blood Proteins; D014991:Xylazine; D013890:Thiourea; C005277:alpha-naphthyl thiourea