Veterinary Medicine Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD;, Email:
Aerobiology, Animal Clinical Pathology, and Telemetry Branch, Veterinary Medicine Division, USAMRIID, Frederick, MD.
Comp Med. 2024 Apr 1;74(2):81-91. doi: 10.30802/AALAS-CM-23-000069. Epub 2024 Mar 21.
Plethysmography is employed in nonhuman primates (NHPs) to calculate respiratory minute volume and determine the exposure time required to deliver an aerosol at the target dose. Anesthetic drugs can impact breathing parameters like steady-state minute volume (SSMV) central to aerosol dosing. Alfaxalone-midazolam mixtures (AM) provide superior parameters for plethysmography in cynomolgus macaques. An obstacle to the use of AM is the volume required to anesthetize via intramuscular injection. A more concentrated formulation of alfaxalone will reduce injection volumes and refine AM protocols. The purpose of this study was to compare AM using the Indexed 10-mg/mL (AM10) formulation compared with an investigational 40-mg/mL (AM40) formulation for IM administration in cynomolgus macaques undergoing plethysmography. We hypothesized that AM10 and AM40 would show no difference in quality of anesthesia (QA), duration of anesthesia, SSMV, accumulated minute volume (AMV), and side effects. We also hypothesized that female macaques would have a longer duration of anesthesia compared with males using both formulations. The study used 15 cynomolgus macaques comprised of 8 females and 7 males. NHPs were compared between 2 separate and randomized anesthetic events no less than one week apart. Each animal served as its own control and animals were randomized by random number generation. Anesthetized NHPs were placed in a sealed plethysmography chamber, and minute volume measurements were calculated every 10 s to determine SSMV. Once SSMV was achieved for 20 min, the trial ended. There were no statistically significant differences between AM10 and AM40 for duration of anesthesia, SSMV, AMV, side effects, or QA. AM40 had a significantly smaller injection volume. Females did not show a significantly longer median duration of anesthesia using either of the alfaxalone formulations. Overall, AM40 offers a more humane anesthetic than AM10 for plethysmography in cynomolgus macaques.
体积描记法用于非人类灵长类动物（NHPs）计算呼吸分钟量，并确定输送气溶胶达到目标剂量所需的暴露时间。麻醉药物会影响呼吸参数，如稳态分钟量（SSMV），这是气溶胶给药的核心。阿法沙龙-咪达唑仑混合物（AM）为食蟹猴的体积描记法提供了更好的参数。AM 的一个障碍是通过肌肉注射麻醉所需的体积。阿法沙龙的更浓缩配方将减少注射量并改进 AM 方案。本研究旨在比较使用Indexed 10-mg/mL（AM10）配方的 AM 与用于接受体积描记术的食蟹猴肌肉内给药的研究性 40-mg/mL（AM40）配方，用于比较。我们假设 AM10 和 AM40 在麻醉质量（QA）、麻醉持续时间、SSMV、累积分钟量（AMV）和副作用方面没有差异。我们还假设两种配方中，雌性猕猴的麻醉持续时间比雄性长。该研究使用了 15 只食蟹猕猴，其中包括 8 只雌性和 7 只雄性。NHPs 在至少相隔一周的 2 个单独的随机麻醉事件之间进行比较。每个动物都是自己的对照，动物通过随机数生成随机分组。麻醉后的 NHPs 被放置在密封的体积描记室中，每 10 秒计算一次分钟量测量值以确定 SSMV。一旦 SSMV 达到 20 分钟，试验结束。AM10 和 AM40 在麻醉持续时间、SSMV、AMV、副作用或 QA 方面没有统计学差异。AM40 的注射量明显较小。两种阿法沙龙配方均未显示女性的中位麻醉持续时间明显更长。总体而言，对于食蟹猴的体积描记术，AM40 比 AM10 提供了更人性化的麻醉。
