Besch T K, Ruble D L, Gibbs P H, Pitt M L
Veterinary Medicine Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Lab Anim Sci. 1996 Oct;46(5):539-44.
When one is using nonhuman primates for studying the inhalation of infective or toxic agents, a respiratory minute volume (MV) range of +/- 50 ml is desirable to ensure the accurate delivery of calculated doses of the aerosolized agent. When one is working with highly infective or toxic agents, it is desirable to anesthetize the animals and to separate the plethysmograph, used to measure MV, from the aerosol chamber, used to administer agents, in order to minimize decontamination procedures and to maximize safety. In our laboratory the sequential completion of these procedures requires at least 20 min. Therefore it is necessary to find an anesthetic that achieves a +/- 50 ml steady-state MV for at least 20 min and that does not change when an animal is transported from one apparatus to another. Using 2.6- to 4.0-kg, 14- to 18-month-old rhesus macaques, we determined that tiletamine/zolazepam induced a steady-state MV of 48 +/- 17.8 min, beginning 21.5 +/- 4.7 min after injection of the anesthetic agent. This MV did not significantly change when animals were transported. The use of ketamine and ketamine/acepromazine resulted in a steady-state MV period of 11.5 +/- 4.5 and 22.0 +/- 7.9 min respectively. When we compared these findings with previously reported mathematical estimations of MV based on functions of weight or respiratory rate, we further determined that the accurate measurement of MV before each aerosol exposure was critical for calculating inhaled doses of the agent.
当使用非人类灵长类动物研究感染性或毒性制剂的吸入情况时，呼吸分钟通气量（MV）范围在±50 ml是理想的，以确保雾化制剂计算剂量的准确输送。当使用高感染性或毒性制剂时，为了尽量减少净化程序并最大限度地提高安全性，需要对动物进行麻醉，并将用于测量MV的体积描记器与用于给药的气溶胶室分开。在我们实验室，依次完成这些程序至少需要20分钟。因此，有必要找到一种麻醉剂，使其能在至少20分钟内达到±50 ml的稳态MV，并且当动物从一个设备转移到另一个设备时不会改变。使用体重2.6至4.0 kg、14至18个月大的恒河猴，我们确定替来他明/唑拉西泮在注射麻醉剂后21.5±4.7分钟开始诱导出48±17.8分钟的稳态MV。当动物转移时，这个MV没有显著变化。使用氯胺酮和氯胺酮/乙酰丙嗪分别导致稳态MV期为11.5±4.5分钟和22.0±7.9分钟。当我们将这些发现与先前报道的基于体重或呼吸频率函数的MV数学估计值进行比较时，我们进一步确定在每次气溶胶暴露前准确测量MV对于计算制剂的吸入剂量至关重要。
