Department of Interdisciplinary Life Sciences, Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria.
Department of Chemistry, Institute of Chemistry of Renewable Resources, BOKU - University of Natural Resources and Life Sciences, Vienna, Austria.
Vet Rec. 2021 Jul;189(1):e76. doi: 10.1002/vetr.76. Epub 2021 Feb 19.
Opioid-induced respiratory compromise remains a significant challenge in etorphine-immobilised wildlife. Serotonergic agonists offer a potential avenue for preventing or treating opioid-induced respiratory compromise. We therefore aimed to determine whether the selective 5-hydroxytryptamine receptor 4 (5-HT4) agonist, BIMU-8, reverses opioid-induced respiratory compromise in etorphine-immobilised goats.
Seven healthy adult goats were immobilised with etorphine, then treated with BIMU-8 or sterile water 5 minutes later in a randomised, prospective cross-over study. Cardiorespiratory variables were measured at 1-minute intervals from 4 minutes before etorphine to 15 minutes after its administration. Arterial blood gas analyses were also performed before and after etorphine administration and the respective treatments.
Intravenous injection of BIMU-8 attenuated etorphine-induced respiratory compromise, as indicated by improvements, compared to baseline and between treatments, in respiratory rate (f ), peripheral arterial blood oxygen saturation (SpO ), partial pressure of arterial oxygen (PaO ) and the alveolar-arterial oxygen partial pressure gradient (P(A-a)O ). BIMU-8 caused an increase in heart rate and a temporary decrease in arterial blood pressure. Mild movements and slight muscle spasm occurred but BIMU-8 did not reverse immobilisation.
Our results indicate that BIMU-8 may be a potential drug candidate for the treatment, or prevention, of etorphine-induced respiratory compromise in immobilised ungulates.
在使用依托咪酯固定的野生动物中,阿片类药物引起的呼吸抑制仍然是一个重大挑战。5-羟色胺能激动剂为预防或治疗阿片类药物引起的呼吸抑制提供了一种潜在的途径。因此,我们旨在确定选择性 5-羟色胺受体 4(5-HT4)激动剂 BIMU-8 是否能逆转依托咪酯固定的山羊的阿片类药物引起的呼吸抑制。
在一项随机、前瞻性交叉研究中,7 只健康成年山羊用依托咪酯固定,5 分钟后用 BIMU-8 或无菌水治疗。从依托咪酯给药前 4 分钟到给药后 15 分钟,每隔 1 分钟测量心肺变量。在依托咪酯给药前后和相应治疗时还进行了动脉血气分析。
与基线和治疗之间相比,静脉注射 BIMU-8 减轻了依托咪酯引起的呼吸抑制,表现为呼吸频率(f )、外周动脉血氧饱和度(SpO )、动脉血氧分压(PaO )和肺泡-动脉血氧分压差(P(A-a)O )的改善。BIMU-8 引起心率增加和短暂的动脉血压下降。出现了轻微的运动和肌肉痉挛,但 BIMU-8 并没有逆转固定状态。
我们的结果表明,BIMU-8 可能是治疗或预防依托咪酯固定的有蹄类动物呼吸抑制的潜在候选药物。