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

Tsubokura, Yasuhiro; Kobayashi, Toshio; Oshima, Yutaka; Hashizume, Naoki; Nakai, Makoto; Ajimi, Shozo; Imatanaka, Nobuya

doi:10.2131/jts.41.595

Cited by 21 publications

(19 citation statements)

References 28 publications

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“…Exsanguination is one of the physical methods of euthanasia with rapid relief of pain and suffering and must be done under anesthesia. Sodium pentobarbital is the most common anesthetic agent used before rodent's euthanasia by exsanguination 15 . As reported in several current literatures, sodium pentobarbital is used with different dosages which may impact the study parameters 16,17 .…”

Section: Discussionmentioning

confidence: 99%

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats

Mohamed

Hosney

Bassiony

et al. 2020

Sci Rep

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Rodents are widely used for animal research in Egypt. Pentobarbital is the most common anesthetic agent; however overdoses may affect the experimental outcomes and limit the use of tissues. To investigate the effects of sodium pentobarbital overdoses during exsanguination, three groups (6 rats/ group) of male and female rats were injected i.p. with 50, 100 and 150 mg/kg of sodium pentobarbital, then carotid exsanguination was performed immediately after loss of consciousness. Hypoxiainducible factor 1-alpha (Hif1a) and tumor necrosis factor-alpha (Tnfa) mRNA expressions in liver and kidney organs were evaluated. As well as, serum aminotransferase activities (AST&ALT), glucose, urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels were determined. The histological alterations in liver, kidney and spleen were studied. It was found that Hif1a and Tnfa were significantly overexpressed in the studied organs and serum AST, glucose, creatinine and urea levels were significantly increased after sodium pentobarbital overdoses (100 and 150 mg/kg) compared to 50 mg/kg dose. Similarly, significant increase in MDA and GSH levels of liver, kidney and spleen were noticed. Results showed gender difference where Hif1a and Tnfa levels were significantly overexpressed at high dose of sodium pentobarbital of liver and kidney organs in female more than male rats. Since euthanasia protocol may influence the physiological variables and affect genes' expression, it is recommended to avoid sodium pentobarbital overdose during euthanasia as it may interfere with the biochemical, molecular and histological measurements. In Egypt, rodents are considered the first choice for the majority of animal research and training. Euthanasia of animals is generally performed upon completion of the study or if a humane endpoint has been reached. Last updates of the Canadian Council on Animal Care (CCAC) and American Veterinary Medical Association (AVMA) euthanasia guidelines 1 describe several techniques for successful euthanasia to refine killing methods for rats and other laboratory animals 2. Euthanasia procedures are divided into two main methods; chemical and physical. Ideally, a mechanical method, such as exsanguination, should be implemented after the chemical death. Pentobarbital is an anesthetic agent commonly used in euthanasia. Olsen and Li (2011) reported that sodium pentobarbital is an injectable, fast-acting, central nervous system depressant which acts via GABA receptors to cause a loss of consciousness and cardiovascular depression 3. In the AVMA Guidelines, anesthetic overdose is recommended as an acceptable method of euthanasia. For rodents, overdose of sodium pentobarbital is the most preferable euthanizing agent 4-6. The main reported negative side effects of pentobarbital mono-anesthesia are cardiovascular and respiratory systems depression, decreased arterial blood pressure, peripheral vasodilation, decreased cardiac output and depression of the vasopressor response to hemorrhage 7. Moreover, ...

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Section: Discussionmentioning

confidence: 99%

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats

Mohamed

Hosney

Bassiony

et al. 2020

Sci Rep

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“…It is necessary to prevent body heat loss and carefully ensure that small animals are kept warm when under MMB anesthesia. Medetomidine increases the blood glucose concentration transiently by inhibiting insulin secretion from the pancreatic islets [12], and MMB has been reported to induce hyperglycemia in laboratory animals [13][14][15]22]. Hyperglycemia associated with MMB anesthesia has been attributed to the actions of medetomidine.…”

Section: Discussionmentioning

confidence: 99%

“…General anesthesia, including that induced by MMB, is often associated with depressions of respiration and circulation, and reduction of the general motor activity, neuronal activity and body temperature. In addition, MMB anesthesia causes inhibition of insulin secretion from the islet cells of the pancreas [12], and has been reported to induce hyperglycemia in mice [14], rats [15,22] and hamsters [13].…”

mentioning

confidence: 99%

Comparison of the anesthetic effect by the injection route of mixed anesthesia (medetomidine, midazolam and butorphanol) and the effect of this anesthetic agent on the respiratory function

Shibuta

Yamana

Kashimoto

et al. 2020

The Journal of Veterinary Medical Science

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Recently, a mixture of medetomidine, midazolam and butorphanol (MMB) has been used as an injectable general anesthetic agent for laboratory animals. The purpose of this study was to establish data to encourage practical usage of MMB, and to clarify the effects of MMB on the respiratory function in rats. To compare the anesthetic efficacy between the injection routes, the anesthetic effects of MMB by subcutaneous (s.c.) or intraperitoneal (i.p.) injection were evaluated in rats. To assess the respiratory function, the blood gas parameters and electrolytes were assessed in serial venous blood samples collected from before s.c. injection of MMB to 270 min after the injection. Recovery from anesthesia and the respiratory changes after atipamezole injection at 30 min after MMB injection was also examined. Subcutaneous injection of MMB was associated with more rapid induction and a longer duration of anesthesia as compared to i.p. injection. The blood gas analysis findings showed MMB had effects on respiratory function, that is, elevations of the partial pressures of carbon dioxide and bicarbonate and reduction of the blood pH. Atipamezole injection resulted in recovery from the MMB-induced anesthetic effect as well as respiratory depression. In conclusion, MMB provides more effective anesthesia administered by s.c. injection compared to i.p. injection and induces respiratory change. These changes were counteracted by atipamezole. Therefore, we recommend MMB administered by s.c. injection for anesthesia, followed by injection of atipamezole after the operative procedure to allow recovery.

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“…The MMB anesthetic drastically altered plasma GLU and insulin levels in hamsters as well as in mice and rats [ 18 , 21 ]. These alterations by the MMB mixture are exclusively due to an α2-adrenoreceptor agonist, medetomidine, which inhibits insulin secretion from the pancreatic β-cells and therefore increases the blood GLU levels [ 1 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the mixture of medetomidine, midazolam and butorphanol (MMB) has been recognized as favorable anesthetic in laboratory rodents, such as mice, rats and cotton rats [ 12 , 13 , 15 , 17 ]. Although the MMB mixture provides sufficient anesthesia and is counteracted by atipamezole, a medetomidine antagonist, this anesthetic agent alters some biochemical parameters in mice and rats [ 18 , 21 ].…”

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confidence: 99%

Effects of a mixture of medetomidine, midazolam and butorphanol on anesthesia and blood biochemistry and the antagonizing action of atipamezole in hamsters

Nakamura

Karakida

Dantsuka

et al. 2017

The Journal of Veterinary Medical Science

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Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.

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

Cited by 21 publications

References 28 publications

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats

Comparison of the anesthetic effect by the injection route of mixed anesthesia (medetomidine, midazolam and butorphanol) and the effect of this anesthetic agent on the respiratory function

Effects of a mixture of medetomidine, midazolam and butorphanol on anesthesia and blood biochemistry and the antagonizing action of atipamezole in hamsters

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