Abstract
Anesthetic protocols for murine models are varied within the literature and medetomidine has been implicated in the development of urethral plugs in male mice. Our objective was to evaluate the combination of butorphanol, dexmedetomidine, and tiletamine-zolazepam. A secondary objective was to identify which class of agent was associated with urethral obstructions in male mice. BALB/c male (n = 13) and female (n = 23) mice were assigned to dexmedetomidine and tiletamine-zolazepam with or without butorphanol or to single agent dexmedetomidine or tiletamine-zolazepam. Anesthesia was achieved in 58% (14/24) of mice without butorphanol and in 100% (24/24) of mice with butorphanol. The combination of dexmedetomidine (0.2 mg/kg), tiletamine-zolazepam (40 mg/kg), and butorphanol (3 mg/kg) resulted in an induction and anesthetic duration of 12 and 143 minutes, respectively. Urethral obstructions occurred in 66% (25/38) of trials in male mice that received dexmedetomidine with a mortality rate of 38% (5/13). Tiletamine-zolazepam, when used alone, resulted in a 0% (0/21) incidence of urethral obstructions. Combination use of dexmedetomidine, tiletamine-zolazepam, and butorphanol results in a longer and more reliable duration of anesthesia than the use of dexmedetomidine and tiletamine-zolazepam alone. Dexmedetomidine is not recommended for use in nonterminal procedures in male mice due to the high incidence of urethral obstructions and resultant high mortality rate.
Highlights
Optimized injectable and inhalational anesthetic protocols for hours-long anesthesia are essential for laboratory animal research
The occurrence of urethral obstructions with the use of medetomidine and ketamine is presumed to be due to the use of medetomidine, as ketamine-xylazine anesthesia has not been associated with this adverse effect [12]
Use of dexmedetomidine and tiletamine-zolazepam was poor at inducing a reliable plane of anesthesia and increased dosages resulted in a higher mortality rate
Summary
Optimized injectable and inhalational anesthetic protocols for hours-long anesthesia are essential for laboratory animal research. Many laboratories do not have the ability to use inhalational vapor anesthesia, necessitating the use of injectable anesthetics. Researchers have utilized a wide array of injectable anesthetic protocols including the use of barbiturates, ketamine, or xylazine with varying success [1,2,3,4,5,6,7,8,9]. The use of dexmedetomidine in conjunction with tiletamine-zolazepam with or without the addition of an opioid as an anesthetic protocol has yet to be evaluated in a mouse model. The occurrence of urethral obstructions with the use of medetomidine and ketamine is presumed to be due to the use of medetomidine, as ketamine-xylazine anesthesia has not been associated with this adverse effect [12]
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