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  • 标题:Assessing anesthetic activity through modulation of the membrane dipole potential
  • 本地全文:下载
  • 作者:Benjamin Michael Davis ; Jonathan Brenton ; Sterenn Davis
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2017
  • 卷号:58
  • 期号:10
  • 页码:1962-1976
  • DOI:10.1194/jlr.M073932
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:There is great individual variation in response to general anesthetics (GAs) leading to difficulties in optimal dosing and sometimes even accidental awareness during general anesthesia (AAGA). AAGA is a rare, but potentially devastating, complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel personalized screening techniques to accurately predict a patient’s response to GAs and the risk of AAGA remains an unmet clinical need. In the present study, we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anesthetic activity using a well-described inducer/noninducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anesthetic action. We show that the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), but not the structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F6), to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome the limitations associated with the alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with noninvasive retinal imaging technologies, we propose that this technique could provide a novel and noninvasive technique to monitor GA susceptibility and identify patients at risk of AAGA.
  • 关键词:cholesterol ; diagnostic tools ; eye ; lipid rafts ; model membranes ; accidental awareness during general anesthesia ; retina ; di-8-ANEPPs ; fluorescence spectroscopy
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