在 C57BL/6J 小鼠(Mus musculus)中使用美托咪定/瓦替诺生与氯胺酮和丁丙诺啡-ER 的组合诱导全身麻醉。

Krystal Tien, Benjamin Franco, Eden D Alamaw, Katechan Jampachairsi, Kerriann Casey, Monika Huss, Cholawat Pacharinsak
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引用次数: 0

摘要

美托咪定/伐替诺生(Zenalpha®)是一种新型麻醉组合剂,可用作狗的镇静剂和镇痛剂。在保持镇静和镇痛效果的同时,华替诺生可最大程度地减少与美托咪定给药相关的心肺不良反应。在这项研究中,我们评估了泽纳尔法与氯胺酮和丁丙诺啡缓释剂(ER)的3种剂量组合与恶嗪与氯胺酮和丁丙诺啡缓释剂(ER)用于C57BL/6J小鼠麻醉的临床安全性和有效性比较。我们假设,与使用 8 毫克/千克的甲苯噻嗪进行麻醉相比,使用 0.5 毫克/千克的 Zenalpha 会更可靠地提供手术麻醉平面、更低的死亡率和更少的不良生理效应。对十周大的雄性和雌性 C57BL/6J 小鼠随机皮下注射四种混合麻醉剂中的一种:氯胺酮(80 毫克/千克)和丁丙诺啡-ER(0.5 毫克/千克)加 1) 异丙嗪(8 毫克/千克;XKB);2) Zenalpha(0.25 毫克/千克;ZKB/0.25);3) Zenalpha(0.5 毫克/千克;ZKB/0.5);或 4) Zenalpha(1.0 毫克/千克;ZKB/1.0)。给药后,我们通过测量右反射和爪退缩反射(PWR)消失的时间来评估麻醉诱导时间。在右反射消失后,每隔 5 分钟监测一次生理参数,包括心率、呼吸频率、血氧饱和度、间接平均动脉血压、体温、下颌张力和皮肤颜色。注射麻醉药物(TA)30 分钟后,注射阿替帕米唑(1 毫克/千克,皮下注射)。恢复时间通过脉搏波速度、右侧反射和行走的恢复时间来确定。对小鼠进行麻醉后 3 天的监测。结果包括1)ZKB 麻醉以剂量依赖的方式导致脉搏波速度减慢;2)在 100% O₂下,XKB 和 ZKB 小鼠的生理参数相似;3)ZKB 组的恢复时间更长,中高剂量组的死亡率为 20% 至 30%。我们的结论是,与使用 8 毫克/千克的甲苯噻嗪麻醉相比,使用 0.5 毫克/千克的 Zenalpha 麻醉能更可靠地产生手术麻醉平面,但也会导致平均动脉压下降和死亡率上升。我们建议使用 Zenalpha(0.25 至 1.0 毫克/千克)、80 毫克/千克氯胺酮和 0.5 毫克/千克丁丙诺啡-ER 对 C57BL/6 小鼠进行全身麻醉,同时补充 100% 氧气和阿替巴唑。
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General Anesthesia Induced by a Combination of Medetomidine/Vatinoxan with Ketamine and Buprenorphine-ER in C57BL/6J Mice (Mus musculus).

Medetomidine/vatinoxan (Zenalpha®) is a novel anesthetic combination used as a sedative and analgesic in dogs. Vatinoxan minimizes adverse cardiopulmonary effects associated with medetomidine administration while preserving sedation and analgesia. In this study, we evaluated the clinical safety and efficacy of 3 dosage combinations of Zenalpha with ketamine and buprenorphine extended release (ER) as compared with xylazine with ketamine and buprenorphine-ER for anesthesia of C57BL/6J mice. We hypothesized that anesthesia with 0.5 mg/kg of Zenalpha would more reliably provide a surgical anesthetic plane, lower mortality, and fewer adverse physiologic effects as compared with anesthesia with 8 mg/kg of xylazine. Ten-week-old male and female C57BL/6J mice were randomly administered 1 of 4 anesthetic cocktails subcutaneously: ketamine (80 mg/kg) and buprenorphine-ER (0.5 mg/kg) with 1) xylazine (8 mg/kg; XKB); 2) Zenalpha (0.25 mg/kg; ZKB/0.25); 3) Zenalpha (0.5 mg/kg; ZKB/0.5); or 4) Zenalpha (1.0 mg/kg; ZKB/1.0). Following drug administration, we assessed the anesthesia induction time by measuring the time to loss of righting reflex and loss of paw withdrawal reflex (PWR). Upon reaching a loss of righting reflex, physiologic parameters including heart rate, respiratory rate, oxygen saturation, indirect mean arterial blood pressure, body temperature, jaw tone, and skin color were monitored every 5 min. Thirty minutes after anesthetic drug administration (TA), atipamezole (1 mg/kg SC) was administered. Recovery time was determined through time until return of PWR, righting reflex, and ambulation. Mice were monitored for 3 d postanesthesia. Results included: 1) ZKB anesthesia caused loss of PWR in a dose-dependent manner; 2) physiologic parameters were similar between XKB and ZKB mice by TA in 100% O₂; 3) ZKB groups took longer to recover and had a 20% to 30% mortality rate in the mid-to-high dosage groups. We conclude that anesthesia with 0.5 mg/kg of Zenalpha more reliably produced a surgical anesthetic plane but also led to decreased mean arterial pressure and increased mortality as compared with anesthesia with 8 mg/kg of xylazine. We recommend using Zenalpha (0.25 to 1.0 mg/kg) with 80 mg/kg ketamine and 0.5 mg/kg buprenorphine-ER to provide general anesthesia in C57BL/6 mice, along with supplemental 100% oxygen and atipamezole.

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