Sedation Efficacy of Midazolam in Conjunction with Ketamine and Alfaxalone in Female Laboratory Guinea Pigs (Cavia porcellus).

Guinea pigs have been integral as models used in biomedical research, making significant contributions to nutritional, auditory, immunologic, and hypersensitivity studies, and necessitating the routine need for sedation in laboratory settings. The ketamine-xylazine (KX) combination has been the standard sedation protocol for decades. However, due to the adverse effects and abuse potential of xylazine, this study explores the possibility of substituting xylazine with midazolam and examines the combined use of midazolam with ketamine and alfaxalone in female laboratory guinea pigs. Our findings indicate that KX facilitates the fastest induction and longest duration of sedation compared with other sedatives, including ketamine-midazolam (KM), which, despite its rapid induction, results in significantly shorter sedation durations. KX also ensures a deeper anesthetic depth and greater odds of loss of withdrawal and inguinal reflexes, in contrast to KM and alfaxalone-midazolam (AM), under which only 15% of the animals lost these reflexes. In terms of cardiopulmonary function, KM led to an increased heart rate attributed to elevated sympathetic activity. All 4 sedative protocols lead to respiratory depression, except KM, which causes minimal reduction. Adverse events varied, with 75% of animals experiencing injection site reactions after KX administration and 67% exhibiting regurgitation post-KM administration. No adverse events were reported for the AM combination, suggesting its safer profile. In conclusion, while KX remains the superior protocol for sedation due to its efficiency, reliability, and minimal impact on physiologic parameters, midazolam is not a preferable alternative to replace xylazine. Its increased sympathetic tone, hyperesthesia, and shorter action duration, coupled with a higher potential for adverse events, limit its suitability to combine with ketamine in guinea pig sedation. However, when midazolam is used in conjunction with safer alternatives like alfaxalone, it presents a viable sedation strategy, emphasizing the need for further research into optimizing sedative combinations for laboratory guinea pigs.

A Comparison of Three Anesthetic Drug Combinations for Use in Inducing Surgical Anesthesia in Female Guinea Pigs (Cavia porcellus).

Guinea pigs are often used in translational research, but providing them with safe and effective anesthesia is a challenge. Common methods like inhalant anesthesia and injectable ketamine/xylazine induce surgical anesthesia but can negatively affect cardiovascular, respiratory, and thermoregulatory systems and complicate the interpretation of research outcomes. Several alternative anesthetic regimens have been investigated, but none have consistently achieved a surgical plane of anesthesia. Therefore, identifying an anesthetic regimen that achieves a stable state of the surgical plane of anesthesia while preserving cardiorespiratory function would be a valuable contribution. To address this issue, we compared the efficacy of 3 anesthetic combinations in female Dunkin-Hartley guinea pigs: 1) alfaxalone, dexmedetomidine, and fentanyl (ADF); 2) alfaxalone, midazolam, and fentanyl (AMF); and 3) alfaxalone, midazolam, fentanyl, and isoflurane (AMFIso). We monitored anesthetic depth, heart rate, oxygenation, respiratory rate, respiratory effort, blood pressure, and body temperature every 15 min from injection to recovery. We also recorded the time to loss of righting reflex, duration of anesthesia, and time to achieve a surgical plane. The results showed no statistically significant differences in induction and recovery times among the groups. In the AMFIso group, 100% of the animals achieved a surgical plane of anesthesia, whereas only 10% of the animals in the AMF group reached that level. None of the animals in ADF group reached a surgical plane of anesthesia. Respiratory rate was significantly lower in the AMFIso as compared with the ADF group (P < 0.001) but was not different between the AMF and ADF groups. Temperature was significantly lower in the AMFIso group as compared with both the ADF and AMF groups (P < 0.001). In conclusion, both combinations of solely injectable anesthetics assessed in this study can be used for short, nonpainful procedures without significant cardiorespiratory depression. However, for mildly to moderately painful surgical procedures, the addition of an inhalant anesthetic like isoflurane is necessary for female guinea pigs.

Effects of Housing Density on Reproductive Performance, Intracage Ammonia, and Welfare of Mice Continuously Housed as Breeders in Standard Mouse and Rat Caging.

Maintaining compliance with cage density recommendations in The Guide for the Care and Use of Laboratory Animals precludes continuous trio breeding in standard-sized mouse cages. This study evaluated and compared several parameters of reproductive performance, intracage ammonia concentration, and fecal corticosterone levels in 2 strains of mice, C57BL/6J (B6) and B6.129S(Cg)-Stat1tm1Dlv/J (STAT1-/-), housed as continuous breeding pairs or trios in standard-sized mouse cages, and continuous breeding trios in standard-sized rat cages. Reproductive performance data indicated that STAT1-/- trios raised in rat cages weaned significantly more pups per litter than did STAT1-/- trios raised in mouse cages, and B6 mice had higher pup survival rates at weaning than did STAT1-/- mice in mouse cages housing continuous breeding trios. In addition, the Production Index was significantly higher for B6 breeding trios in rat cages than for B6 trios in mouse cages. Intracage ammonia concentration increased with cage density, with significantly higher ammonia concentrations in mouse cages housing trios compared with rat cages housing trios. However, fecal corticosterone levels did not differ significantly regardless of genotype, breeding configuration, or cage size, and daily health checks revealed no clinical abnormalities under any of the conditions evaluated. These results suggest that, although continuous trio breeding in standard-sized mouse cages does not seem to compromise mouse welfare, it offers no advantage in reproductive performance compared with pair breeding, and in some cases, it might be disadvantageous in this regard. Further, high intracage ammonia in mouse cages containing breeding trios might necessitate more frequent cage changes.

Rapid Recovery and Short Duration Anesthesia after Low Dose Ketamine and High Dose Dexmedetomidine in Rhesus Macaques (Macaca mulatta).

Anesthesia in rhesus macaques is required for many procedures. Although ketamine is the backbone of most anesthetic protocols, tolerance to the drug can develop, resulting in the need for higher doses to provide sufficient restraint. Combination with other drugs, such as α-agonists, can be ketamine-sparing, providing for sufficient restraint at lower ketamine doses. In addition, because α-agonists are reversible, recovery from anesthesia has the potential to be much shorter. We hypothesized that use of a low dose of ketamine with a high dose of dexmedetomidine, an α2 receptor selective agonist, in male and female rhesus macaques less than 15 y of age would provide adequate anesthesia for short procedures and that recovery would be faster than in macaques given a higher dose of ketamine (10 mg/kg) alone. We found that the combination, in conjunction with atipamezole for reversal, provided smooth induction of anesthesia and significantly shorter recovery time than did ketamine alone, with no significant effects of sex. The combination of low dose ketamine and high dose dexmedetomidine also provided a 30-min window of anesthesia with analgesia sufficient for mild to moderately painful procedures.

Effects of Buprenorphine, Methylnaltrexone, and Their Combination on Gastrointestinal Transit in Healthy New Zealand White Rabbits.

Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these agents. Methylnaltrexone is a peripheral opioid antagonist that ameliorates opioid-induced gastrointestinal stasis in others species yet preserves the analgesic effects of buprenorphine. We evaluated whether methylnaltrexone reversed buprenorphine-induced gastrointestinal stasis in 8 healthy male New Zealand White rabbits. To measure gastrointestinal transit time, each rabbit received 20 barium-filled spheres through an orogastric tube. Rabbits then received 4 treatments in random order: buprenorphine (0.05 mg/kg SC), methylnaltrexone (1 mg/kg SC), both agents combined (B+M), or normal saline (control) every 12 h for 2 d. Fecal production was measured every 6 h, and water and food consumption, and body weight, were measured daily, for 5 d after each treatment. The time to appearance of the first sphere was significantly longer for buprenorphine group than for control and methylnaltrexone groups. Daily fecal output was lowest for buprenorphine and B+M, intermediate for control, and highest for methylnaltrexone. Water and food consumption were lower for groups buprenorphine and B+M than for control and methylnaltrexone. Body weight was not affected. In conclusion, treatment with buprenorphine 0.05 mg/kg BID for 2 d in healthy rabbits decreased food and water consumption, prolonged gastrointestinal transit time and decreased the fecal output. Coadministration of methylnaltrexone at 1 mg/kg did not alleviate these negative side effects.