Assessing anesthetic activity through modulation of the membrane dipole potential

• DOI: 10.1194/jlr.m073932
• Publication Date: 2017-08-18T01:00:15Z
• Authors: Benjamin Michael ...; Jonathan Brenton; Sterenn Davis; Ehtesham Shamsher; Claudia Sisa; Ljuban Grgic; M. Francesca Cord...
• Keywords: Modulation (music)

There is great individual variation in response to general anesthetics (GAs) leading difficulties optimal dosing and sometimes even accidental awareness during anesthesia (AAGA). AAGA a rare, but potentially devastating, complication affecting between 0.1% 2% of patients undergoing surgery. The development novel personalized screening techniques accurately predict patient's GAs the risk remains an unmet clinical need. In present study, we demonstrate principle using fluorescent reporter membrane dipole potential, di-8-ANEPPs, as method monitor anesthetic activity well-described inducer/noninducer pair. potential has previously been suggested contribute mechanism action. We show that fluorescence ratio di-8-ANEPPs changed physiological concentrations anesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), not structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F6), artificial membranes vitro retinal cell systems. Modulation provides explanation overcome limitations associated with alternative membrane-mediated mechanisms GA Furthermore, by combining this technique noninvasive imaging technologies, propose could provide susceptibility identify at AAGA. General are potent reversible inducers muscle relaxation, analgesia, immobility, reflex suppression, sleep, without which many aspects modern medicine would be impossible. For reason, widely considered one most important medical advances last 200 years. However, action diverse family molecules poorly understood (1.Kopp Lugli A. Yost C.S. Kindler C.H. Anaesthetic mechanisms: update on challenge unravelling mystery anaesthesia.Eur. J. Anaesthesiol. 2009; 26: 807-820Crossref PubMed Scopus (63) Google Scholar), patient response. This problem, complete understanding will permit design improved safety activity, more accurate predictions individual's GA. 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Before subtraction, spectrum normalized integrated areas reflect spectral shifts then appropriate three-point moving applied noise. series wavelengths 420 520 emission wavelength 670 nm. Additions 1, 2.5, made approximately 120 s baseline continued until change signal observed (typically 300 600 s). Data fit linear regression (indicative significant ligands) plateau followed one-phase exponential decay equation 1: Y=IF{X<X0,Y0,Plateau+(Y0−Plateau)×exp[−K×(X−X0)]}(Eq. X0 begins (fixed GA/non-GA addition), Y0 Y value X0, infinite time, K rate constant expressed s−1. preferred case extra sum-of-squares F-test simpler (linear regression) selected, P < 0.05. ratios converted estimates calibration Starke-Peterkovic (equation 2): ψd =R+ab(Eq. 2) R intensity fluorescen