咪达唑仑/右美托咪定与丁丙诺啡或缓释丁丙诺啡麻醉对 C57BL/6 小鼠的影响

Lisa Hagan, Emily M David, Alanna R Horton, James O Marx
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引用次数: 0

摘要

常用的可注射麻醉剂组合(如氯胺酮和异丙嗪,加或不加乙酰丙嗪)在不同个体间的效果差异很大,剂量反应曲线较浅,而且不能提供长期镇痛效果。这些缺点表明,继续努力为小鼠开发安全有效的可注射麻醉组合非常重要。在本研究中,我们设计了一系列实验来验证使用右美托咪定和咪达唑仑为非疼痛性手术提供化学约束,以及添加丁丙诺啡或缓释丁丙诺啡为 C57BL/6J 小鼠提供可靠的手术麻醉平面。意识丧失的定义是右反射丧失;手术麻醉平面的定义是右反射丧失和后爪受到 300 克有害刺激后的蹬地回缩丧失。腹腔注射 0.25 毫克/千克右美托咪定和 6 毫克/千克咪达唑仑可产生 LORR,足以进行无痛或无创手术,但在 20 只小鼠中,有 19 只小鼠在测试中未达到手术平面。在皮下注射 0.1 毫克/千克丁丙诺啡或 1 毫克/千克丁丙诺啡-ER 后,30 只小鼠中有 29 只实现了手术平面麻醉。随后,通过对 6 只小鼠成功实施开腹手术,对该方案的安全性和有效性进行了测试。在所有试验中都没有出现死亡,而且在给小鼠注射 1 毫克/千克阿替帕米唑(IP)后,所有小鼠都在 11 分钟内恢复了右反射。本研究中开发的麻醉方案是安全的、可逆的,并且包含了以往研究表明可在术后立即镇痛的镇痛剂。丁丙诺啡-ER 可以安全地替代丁丙诺啡,以获得更持久的镇痛效果。
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Effects of Midazolam/Dexmedetomidine with Buprenorphine or Extended-release Buprenorphine Anesthesia in C57BL/6 Mice.

The effects of commonly used injectable combinations of anesthetics such as ketamine and xylazine, with or without acepromazine, vary widely across individuals, have a shallow-dose response curve, and do not provide long-term analgesia. These drawbacks indicate the importance of continuing efforts to develop safe and effective injectable anesthetic combinations for mice. In this study, a series of experiments was designed to validate the use of dexmedetomidine and midazolam to provide chemical restraint for nonpainful procedures and the addition of buprenorphine or extended-release buprenorphine to reliably provide a surgical plane of anesthesia in C57BL/6J mice. Loss of consciousness was defined as the loss of the righting reflex (LORR); a surgical plane of anesthesia was defined as the LORR and loss of pedal withdrawal after application of a 300 g noxious stimulus to a hind paw. The combination of intraperitoneal 0.25 mg/kg dexmedetomidine and 6 mg/kg midazolam produced LORR, sufficient for nonpainful or noninvasive procedures, without achieving a surgical plane in 19 of 20 mice tested. With the addition of subcutaneous 0.1 mg/kg buprenorphine or 1 mg/kg buprenorphine-ER, 29 of 30 mice achieved a surgical plane of anesthesia. The safety and efficacy of the regimen was then tested by successfully performing a laparotomy in 6 mice. No deaths occurred in any trial, and, when administered 1 mg/kg atipamezole IP, all mice recovered their righting reflex within 11 min. The anesthetic regimen developed in this study is safe, is reversible, and includes analgesics that previous studies have shown provide analgesia beyond the immediate postsurgical period. Buprenorphine-ER can be safely substituted for buprenorphine for longer-lasting analgesia.

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American Society of Laboratory Animal Practitioners Position Statement: Handling and Physical Restraint of Research Animals. American Society of Laboratory Animal Practitioners Position Statement: Definition of Animal Welfare. Effect of Novel High-fat Diet Feeding Methods on Food Wastage, Weight Gain, Hair Coat Grease Accumulation, and Scratching Behavior in C57BL/6NCrl Mice. Identification and Treatment of Fur Mites (Radfordia lemnina) in California Deer Mice (Peromyscus californicus) Using Selamectin. American Society of Laboratory Animal Practitioners Position Statement: Animal Care Principles.
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