Naked mole-rats (Heterocephalus glaber) are members of the family Bathyergidae and are subterranean rodents native to sub-Saharan Africa. Evolutionary adaptations of naked mole-rats have made them useful for studies on aging because they are the rodent species with the longest lifespan, cancer resistance because of their low prevalence of cancers, and hypoxia resistance because of their physiologic adaptations (including a low basal metabolic rate, high Hct, and hemoglobin with high oxygen affinity) that enable them to survive in hypoxic and hypercapnic burrow environments. They also have been used in behavioral studies1,2 because they are a eusocial mammalian species.
Chemical immobilization or anesthesia of mole-rats is often necessary to enable clinicians to perform examinations or diagnostic procedures.3,4 Injectable anesthesia protocols in mole-rats commonly have included the use of combinations of ketamine (15 to 100 mg/kg) and xylazine (0.6 to 8 mg/kg), with little information regarding anesthetic variables.1,3-11 For example, blind mole-rats (Spalax ehrenbergi) have been anesthetized with ketamine (30 to 40 mg/kg) and xylazine (2 mg/kg) administered IP,8 and Ansell mole-rats (Fukomys anselli) have been anesthetized with ketamine (40 mg/kg) and xylazine (5 mg/kg) administered IM.9 In another study,3 Ansell mole-rats and giant mole-rats (Fukomys mechowii) were anesthetized with ketamine (6 mg/kg) and xylazine (2.5 mg/kg) administered IM, which resulted in rapid induction, a light plane of anesthesia, and smooth recovery from anesthesia in both of these species. Given their low basal metabolic rate, compared with that for other mammals of similar size, extrapolation of anesthetic doses reported for other rodent species may not be safe and is not recommended.3 Therefore, additional studies regarding the safety and efficacy of injectable anesthetic regimens in naked mole-rats are required.
Suitable combinations of injectable agents should ideally involve short-acting anesthetics with a wide safety margin that preferably are also reversible.12–16 Regimens that involve SC or IM injection of combinations of ketamine and α2-adrenoceptor agonists are routinely used as a practical method for anesthetizing rodents, especially when inhalation anesthesia equipment is not available (eg, field settings) or an animal cannot readily be intubated because of a narrow oral cavity and overall small body size (eg, mole-rats).13–17
Alfaxalone (3α-hydroxy-5α-pregnane-11, 20-dione) is an increasingly popular option for sedation and anesthesia of rodents. Although the drug is intended primarily for IV administration, it can also be administered via the IM and SC routes.18–21 Alfaxalone is a neuroactive steroid molecule that potentiates γ-aminobutyric acid A receptors, which results in centrally mediated muscle relaxation and anesthesia that is not reversible. The anesthetic profile of alfaxalone resembles that of propofol, and the effects of alfaxalone may be potentiated when the drug is combined with sedatives and analgesics.18–20,22,23 Because alfaxalone does not provide analgesia, premedication with α2-adrenoceptor agonists and opioids can improve the quality of anesthesia, extend the duration of analgesia, and reduce the required dose and volume of alfaxalone.12,18-25 For example, alfaxalone administered alone to guinea pigs provided only light sedation, but administration of a combination of alfaxalone-dexmedetomidine-buprenorphine increased the duration of sedation and immobility but did not result in general anesthesia.20,26 A combination of alfaxalone-medetomidine-butorphanol administered IP and SC to laboratory mice18 and a combination of alfaxalone-dexmedetomidine-butorphanol administered IM to rabbits21 resulted in a surgical plane of anesthesia. Addition of low doses of ketamine, a dissociative, centrally acting antagonist of the N-methyl-d-aspartate receptor, can provide a deeper level of sedation and some analgesia, which can facilitate the performance of more invasive procedures or result in a longer duration of immobilization.27,28
To the authors’ knowledge, data on clinically appropriate injectable anesthetic regimens with a combination of AKD and ABM for use in naked mole-rats have been not published. The objective of the study reported here was to determine the physiologic effects of 2 alfaxalone-based combinations (AKD and ABM) in naked mole-rats. Our primary hypothesis was that both regimens would provide effective immobilization in naked mole-rats. Another hypothesis was that sex of the mole-rats would affect the measured anesthetic variables.
Supported by an internal research grant (MCAT) from the College of Veterinary Medicine at Kansas State University.
The authors declare that there were no conflicts of interest.
The authors thank Elizabeth Loos, Carolyn Mark, Kallie Woodruff, and Sarah Ostrom for technical assistance.
Interquartile (25th to 75th percentile) range
Oxygen saturation as measured by pulse oximetry
Alfaxan, Jurox, Kansas City, Mo.
Ketaset, Hospira, Lake Forest, Ill.
Dexdomitor, Orion Corp, Espoo, Finland.
Torbugesic-SA, Zoetis, Florham Park, NJ.
Midazolam, Hospira, Lake Forest, Ill.
BD Ultra-Fine II, Becton, Dickinson and Co, Franklin Lakes, NJ.
Antisedan, Orion Corp, Espoo, Finland.
Flumazenil, Hikma Farmaceutica, Terrugem, Portugal.
Model 811-B Doppler flow detector, Parks Medical Electronics, Las Vegas, Nev.
BCI 3301, Smiths Medical PM Inc, Waukesha, Wis.
R package, version 3.1-121, R Foundation for Statistical Computing, Vienna, Austria.
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