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埃托啡通过拟交感神经作用在固定的白犀牛中诱发病理生理学,而布托啡诺可减弱这种作用。

Etorphine induces pathophysiology in immobilized white rhinoceros through sympathomimesis that is attenuated by butorphanol.

作者信息

Boesch Jordyn M, Gleed Robin D, Buss Peter E, Tordiffe Adrian S W, Zeiler Gareth E, Miller Michele A, Viljoen Francois, Harvey Brian H, Parry Stephen A, Meyer Leith C R

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, 930 Campus Road, Ithaca, New York 14853, USA.

Veterinary Wildlife Services, South African National Parks, Kruger National Park, Private Bag X402, Skukuza 1350, South Africa.

出版信息

Conserv Physiol. 2025 Apr 4;13(1):coaf009. doi: 10.1093/conphys/coaf009. eCollection 2025.

DOI:10.1093/conphys/coaf009
PMID:40196708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11974248/
Abstract

White rhinoceros are a sentinel species for important ecosystems in southern Africa. Their conservation requires active management of their population, which, in turn, requires immobilization of individuals with an ultra-potent opioid such as etorphine. Unfortunately, when immobilized with etorphine, they develop severe hypoxaemia that may contribute to morbidity and mortality. We hypothesized that (i) etorphine causes sympathetic upregulation that is responsible for physiological complications that produce hypoxaemia and (ii) butorphanol, a partial μ opioid agonist, mitigates sympathetic upregulation, thereby improving arterial oxygen content (CaO) and delivery (DO). Six subadult male white rhinoceros were administered two treatments in random order: etorphine-saline (ES) and etorphine-butorphanol (EB). After intramuscular etorphine (~2.6 μg kg), rhinoceros became recumbent (time 0 min [t0]) and were instrumented. Baseline data were collected at t30, butorphanol (0.026 mg/kg) or 0.9% saline was administered intravenously at t37, and data were collected again at t40 and t50. At baseline, plasma noradrenaline concentration was >40 ng ml, approximately twice that of non-immobilized rhinoceros ( test,  < 0.05); cardiac output (Qt, by thermodilution) and metabolic rate (VO, by spirometry/indirect calorimetry) were greater than predicted allometrically ( test,  < 0.05), and pulmonary hypertension was present. After butorphanol, noradrenaline concentration remained greater than in non-immobilized rhinoceros; in EB, CaO was greater, while Qt, DO, VO, and pulmonary pressures were less than in ES (linear mixed effect model, all  < 0.05). Increased noradrenaline concentration with increased Qt and hypermetabolism supports etorphine-induced sympathetic upregulation. Butorphanol partly attenuated these effects, increasing CaO but reducing Qt and, thus, DO. Since plasma noradrenaline concentration remained increased after butorphanol administration while Qt, DO, and VO decreased, a pathway independent of plasma noradrenaline concentration might contribute to the cardiopulmonary and hypermetabolic effects of etorphine. Developing treatments to combat this sympathomimesis could reduce capture-related morbidity in white rhinoceros.

摘要

白犀牛是南部非洲重要生态系统的指示物种。它们的保护需要对其种群进行积极管理,而这反过来又需要使用超强效阿片类药物如埃托啡对个体进行麻醉。不幸的是,用埃托啡麻醉时,它们会出现严重的低氧血症,这可能导致发病和死亡。我们假设:(i)埃托啡会导致交感神经上调,从而引发产生低氧血症的生理并发症;(ii)布托啡诺,一种部分μ阿片受体激动剂,可减轻交感神经上调,从而提高动脉血氧含量(CaO)和输送量(DO)。六只亚成年雄性白犀牛被随机给予两种处理:埃托啡-生理盐水(ES)和埃托啡-布托啡诺(EB)。肌肉注射埃托啡(约2.6μg/kg)后,犀牛卧倒(时间0分钟[t0])并进行仪器安装。在t30收集基线数据,在t37静脉注射布托啡诺(0.026mg/kg)或0.9%生理盐水,然后在t40和t50再次收集数据。在基线时,血浆去甲肾上腺素浓度>40ng/ml,约为未麻醉犀牛的两倍(检验,<0.05);心输出量(Qt,通过热稀释法)和代谢率(VO,通过肺活量测定法/间接量热法)高于根据体型预测的值(检验,<0.05),并且存在肺动脉高压。注射布托啡诺后,去甲肾上腺素浓度仍高于未麻醉的犀牛;在EB组中,CaO更高,而Qt、DO、VO和肺动脉压力低于ES组(线性混合效应模型,均<0.05)。去甲肾上腺素浓度随着Qt增加和代谢亢进增加,这支持了埃托啡诱导的交感神经上调。布托啡诺部分减弱了这些影响,增加了CaO但降低了Qt,从而降低了DO。由于注射布托啡诺后血浆去甲肾上腺素浓度仍升高,而Qt、DO和VO降低,一条独立于血浆去甲肾上腺素浓度的途径可能导致了埃托啡的心肺和代谢亢进作用。开发对抗这种拟交感神经作用的治疗方法可以降低白犀牛捕获相关的发病率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b104/11974248/bd7e0b35af76/coaf009f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b104/11974248/870e59211637/coaf009f1.jpg
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