Veterinary Medicine Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland;, Email:
Aerobiology, Animal Clinical Pathology, and Telemetry Section, Veterinary Medicine Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland.
Comp Med. 2022 Aug 1;72(4):248-256. doi: 10.30802/AALAS-CM-22-000010. Epub 2022 Jun 30.
Plethysmography is used in nonhuman primates (NHPs) to measure minute volume before aerosol exposure to an agent to calculate total time necessary in the exposure chamber. The consistency of respiratory parameters during the entire exposure time is paramount to ensuring dosing accuracy. Our study sought to validate an alfaxalone-midazolam (AM) anesthetic combination for use in aerosol studies. We hypothesized that AM would provide an adequate duration of anesthesia, achieve and maintain steady state minute volume (SSMV) for 20 min, and have anesthetic quality and side effects comparable to or better than either tiletamine-zolazepam (TZ) and ketamine-acepromazine (KA), the most common anesthetics used for this purpose currently. Two groups of NHPs, one consisting of 15 cynomolgus macaques and one of 15 rhesus macaques, received 3 intramuscular anesthetic combinations (AM, TZ, and KA), no less than one week apart. Anesthetized NHPs were placed in a plethysmograph chamber and their minute volumes were measured every 10 s to determine whether they had achieved SSMV and maintained it for at least 20 consecutive min. Achieving and reliably maintaining an SSMV for at least 20 min facilitates precise aerosol dosing of a challenge agent. Quality of anesthesia, based on the NHP's ability to achieve and maintain SSMV, was higher with AM compared with TZ and KA in both species, and AM had a longer duration of SSMV as compared with TZ and KA in cynomolgus macaques. Average SSMV was larger with AM compared with TZ in cynomolgus macaques, but larger with KA compared with AM in rhesus macaques. Duration of anesthesia was sufficient with all combinations but was longer for TZ than both AM and KA in both species. These results suggest that the AM anesthetic combination would produce the most accurate dosing for an aerosol challenge.
体积描记法用于非人类灵长类动物（NHPs），在气溶胶暴露于一种制剂之前测量分钟量，以计算暴露室中所需的总时间。在整个暴露时间内保持呼吸参数的一致性对于确保剂量准确性至关重要。我们的研究旨在验证一种用于气溶胶研究的麻醉组合，即阿尔法花烷-咪达唑仑（AM）。我们假设 AM 可以提供足够长的麻醉时间，实现并维持 20 分钟的稳定状态分钟量（SSMV），并且具有与目前最常用于此目的的替来他明-唑拉西泮（TZ）和氯胺酮-乙酰丙嗪（KA）相当或更好的麻醉质量和副作用。两组 NHPs，一组由 15 只食蟹猴组成，另一组由 15 只恒河猴组成，至少相隔一周接受 3 种肌内麻醉组合（AM、TZ 和 KA）。麻醉后的 NHPs 被放置在体积描记器室中，每隔 10 秒测量一次他们的分钟量，以确定他们是否达到了 SSMV 并至少维持了 20 分钟。至少 20 分钟内实现并可靠地维持 SSMV 有助于精确地气溶胶给药挑战剂。基于 NHPs 实现和维持 SSMV 的能力，麻醉质量 AM 比 TZ 和 KA 更高，在两种物种中，AM 比 TZ 和 KA 具有更长的 SSMV 持续时间。与 TZ 相比，AM 在食蟹猴中的平均 SSMV 更大，但在恒河猴中，KA 比 AM 更大。所有组合的麻醉时间都足够长，但在两种物种中，TZ 的时间都比 AM 和 KA 长。这些结果表明，AM 麻醉组合将为气溶胶挑战产生最准确的剂量。
