Kint Leila T, Seewoo Bhedita J, Hyndman Timothy H, Clarke Michael W, Edwards Scott H, Rodger Jennifer, Feindel Kirk W, Musk Gabrielle C
Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia.
Centre for Microscopy, Characterisation and Analysis, Research Infrastructure Centres, The University of Western Australia, Perth 6009, Australia.
Animals (Basel). 2020 Jun 18;10(6):1050. doi: 10.3390/ani10061050.
Anaesthetic protocols involving the combined use of a sedative agent, medetomidine, and an anaesthetic agent, isoflurane, are increasingly being used in functional magnetic resonance imaging (fMRI) studies of the rodent brain. Despite the popularity of this combination, a standardised protocol for the combined use of medetomidine and isoflurane has not been established, resulting in inconsistencies in the reported use of these drugs. This study investigated the pharmacokinetic detail required to standardise the use of medetomidine and isoflurane in rat brain fMRI studies. Using mass spectrometry, serum concentrations of medetomidine were determined in Sprague-Dawley rats during medetomidine and isoflurane anaesthesia. The serum concentration of medetomidine for administration with 0.5% (vapouriser setting) isoflurane was found to be 14.4 ng/mL (±3.0 ng/mL). The data suggests that a steady state serum concentration of medetomidine when administered with 0.5% (vapouriser setting) isoflurane can be achieved with an initial subcutaneous (SC) dose of 0.12 mg/kg of medetomidine followed by a 0.08 mg/kg/h SC infusion of medetomidine. Consideration of these results for future studies will facilitate standardisation of medetomidine and isoflurane anaesthetic protocols during fMRI data acquisition.
涉及联合使用镇静剂美托咪定和麻醉剂异氟烷的麻醉方案，越来越多地用于啮齿动物大脑的功能磁共振成像（fMRI）研究。尽管这种联合使用很普遍，但美托咪定和异氟烷联合使用的标准化方案尚未确立，导致这些药物的使用报告存在不一致性。本研究调查了在大鼠脑fMRI研究中标准化使用美托咪定和异氟烷所需的药代动力学细节。使用质谱法，在美托咪定和异氟烷麻醉期间测定了Sprague-Dawley大鼠血清中美托咪定的浓度。发现与0.5%（蒸发器设置）异氟烷联合给药时美托咪定的血清浓度为14.4 ng/mL（±3.0 ng/mL）。数据表明，与0.5%（蒸发器设置）异氟烷联合给药时，美托咪定的稳态血清浓度可通过初始皮下（SC）注射0.12 mg/kg美托咪定，随后以0.08 mg/kg/h的速度皮下输注美托咪定来实现。在未来的研究中考虑这些结果将有助于在fMRI数据采集期间标准化美托咪定和异氟烷的麻醉方案。
