Effects of pentobarbital, isoflurane, or medetomidine–midazolam–butorphanol anesthesia on bronchoalveolar lavage fluid and blood chemistry in rats

• Published in: Journal of toxicological sciences Vol. 41; no. 5; pp. 595 - 604
• Main Authors: Tsubokura, Yasuhiro, Kobayashi, Toshio, Oshima, Yutaka, Hashizume, Naoki, Nakai, Makoto, Ajimi, Shozo, Imatanaka, Nobuya
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2016; Japan Science and Technology Agency
• Subjects: Administration, Inhalation; Albumin; Alveoli; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Anesthesia; Anesthesia - adverse effects; Anesthesia - methods; Anesthetics; Anesthetics, Inhalation - administration & dosage; Anesthetics, Inhalation - toxicity; Animal welfare; Animals; BALF; Biomarkers - blood; Blood; Blood chemistry; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; Bronchus; Butorphanol; Butorphanol - administration & dosage; Butorphanol - toxicity; Chemistry; Dehydrogenase; Dehydrogenases; Disease Models, Animal; Euthanasia; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - toxicity; Inflammation; Inhalation; Injection; Injections, Intraperitoneal; Isoflurane; Isoflurane - administration & dosage; Isoflurane - toxicity; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Lung - drug effects; Lung - immunology; Lung - metabolism; Male; Medetomidine; Medetomidine - administration & dosage; Medetomidine - toxicity; Midazolam; Midazolam - administration & dosage; Midazolam - toxicity; Neutrophils; Nickel; Organic chemistry; Parameters; Pentobarbital; Pentobarbital - administration & dosage; Pentobarbital - toxicity; Pneumonia - blood; Pneumonia - chemically induced; Pneumonia - immunology; Rats, Inbred F344; Respiration; Risk Assessment; Rodents; Toxicity
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.41.595

Bronchoalveolar lavage fluid (BALF) is commonly examined for pulmonary toxicity in animal studies. Two common means of anesthesia before euthanasia and bronchoalveolar lavage in rats are intraperitoneal injection of pentobarbital and inhalation of isoflurane. Medetomidine–midazolam–butorphanol is an alternative anesthesia to pentobarbital for animal welfare; however, the effect of this combination on BALF and blood chemistry is unknown. Here, we compared the effects of anesthesia by intraperitoneal injection of pentobarbital or one of two combinations of medetomidine–midazolam–butorphanol (dose, 0.375-2.0-2.5 or 0.15-2.0-2.5 mg/kg) or by inhalation of isoflurane on BALF and blood chemistry in rats with or without pulmonary inflammation. In BALF, we determined total protein, albumin, lactate dehydrogenase, total cell count and neutrophil count. In serum, we conducted a general chemistry screen. After anesthesia with pentobarbital or isoflurane, there were no significant differences between any of the BALF or blood chemistry parameters with or without inflammation. After anesthesia with either of the combinations of medetomidine–midazolam–butorphanol, lactate dehydrogenase, total cell count, neutrophil count, and almost all of the blood chemistry parameters were comparable with those observed after pentobarbital or isoflurane; however, BALF albumin and serum glucose were significantly increased in rats without inflammation. After the combination of low-dose medetomidine in rats with inflammation, BALF parameters were comparable with those observed after pentobarbital or isoflurane. Our results show that, of the anesthetics examined, inhalation of isoflurane is the most appropriate means of anesthesia when examining BALF or serum for toxicity studies in rats.