Quantification of solute entry into cochlear perilymph through the round window membrane
Quantification of solute entry into cochlear perilymph through the round window membrane
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DOI：
10.1016/s0378-5955(01)00223-4
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发表时间：
2001-04-01
期刊：
影响因子：
2.8
通讯作者：
Ma, YL
中科院分区：
文献类型：
--
作者：
Salt, AN;Ma, YL
通过圆窗膜向内耳给药正变得越来越广泛地用于临床和实验目的。通过这种方法在内耳不同区域达到的实际药物水平尚未确定。本研究利用耳蜗液中溶质运动的模拟来描述豚鼠耳蜗液空间中标记物溶质的分布。模拟参数来自使用标记离子的实验测量。三甲基苯基铵（TMPA）。使用密封在第一和第二圈鼓阶（ST）中的TMPA选择性微电极，在没有体积干扰的情况下监测该离子在耳蜗中的分布。通过用2 mM溶液冲洗完整的圆窗膜，将TMPA应用于外淋巴。在90分钟施用期结束时，在第一圈中，距ST基部1.4mm处的TMPA达到330 μ M的平均浓度（标准偏差（S.D.）147 μ M，n = 8）。TMPA在第二回合。7.5距离ST基部10 mm处的浓度达到15 μ M（S.D. 33 μ M，n = 5）。使用华盛顿大学的CONDITAR流体模拟器（V1.4）（一种可在互联网http://oto.wustl.edu/cochlea/上获得的公共领域程序）解释测量的TMPA浓度变化的时间过程。使用产生与测量值相当的浓度时间过程的参数进行的模拟为：（1）圆窗渗透性：1.9 × 10（-8）cm/s;（2）ST清除半衰期：60 min;（3）纵向外淋巴液流速：4.4 nl/min，从底部到顶部。发现耳蜗顶端区域的溶质浓度主要由溶质扩散的速率确定，由溶质从外淋巴中清除的速率平衡。现在，除非骨性耳囊穿孔，否则纵向外淋巴液不是溶质分布的重要因素。这迅速引起溶质分布的实质性变化。这项研究展示了物质在耳蜗中分布的基本过程，并为了解其他应用物质如何在耳中分布提供了基础。(C)2001 Elsevier Science B. V.保留所有权利。
The administration of drugs to the inner ear via the round window membrane is becoming more widely used for both clinical and experimental purposes. The actual drug levels achieved in different regions of the inner ear by this method have not been established. The present study has made use of simulations of solute movements in the cochlear fluids to describe the distribution of a marker solute in the guinea pig cochlear fluid spaces. Simulation parameters were derived from experimental measurements using a marker ion. trimethylphenylammonium (TMPA). The distribution of this ion in the cochlea was monitored without volume disturbance using TMPA-selective microelectrodes sealed into the first and second turns of scala tympani (ST). TMPA was applied to perilymph by irrigation of the intact round window membrane with 2 mM solution. At the end of a 90 min application period, TMPA in the first turn, 1.4 mm from the base of ST, reached an average concentration of 330 muM (standard deviation (S.D.) 147 muM, n = 8). TMPA in the second turn. 7.5 mm from the base of ST reached a concentration of 15 muM (S.D. 33 muM, n = 5). The measured time courses of TMPA concentration change were interpreted using the Washington University Cochlear Fluids Simulator (V 1.4), a public-domain program available on the internet at http://oto.wustl.edu/cochlea/. Simulations with parameters producing concentration time courses comparable to those measured were: (1) round window permeability: 1.9X10(-8) cm/s; (2) ST clearance half-time: 60 min: (3) longitudinal perilymph flow rate: 4.4 nl/min, directed from base to apex. Solute concentrations in apical regions of the cochlea were found to be determined primarily by the rate at which the solute diffuses, balanced by the rate of clearance of the solute from perilymph. Longitudinal perilymph now was not an important factor in solute distribution unless the bony otic capsule was perforated. which rapidly caused substantial changes to solute distribution. This study demonstrates the basic processes by which substances are distributed in the cochlea and provides a foundation to understand how other applied substances will be distributed in the ear. (C) 2001 Elsevier Science B.V. All rights reserved.