Salt Alec N, Kellner Christian, Hale Shane
Department of Otolaryngology, Box 8115, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Hear Res. 2003 Aug;182(1-2):24-33. doi: 10.1016/s0378-5955(03)00137-0.
Our understanding of the perilymph kinetics of drugs depends largely on data obtained by the analysis of perilymph samples. Although a number of studies have demonstrated qualitatively that perilymph samples may be contaminated by cerebrospinal fluid (CSF), and some investigations adopt specific methods to minimize CSF contamination of their samples, many other studies fail to consider the influence of this potential artifact on their measurements. In the present study we have attempted to quantify the degree of CSF contamination of perilymph samples taken from the basal turn of the guinea pig cochlea using the ionic marker trimethylphenylammonium (TMPA). TMPA solution was irrigated across the round window membrane while a TMPA-selective electrode sealed into the perilymphatic space continuously monitored perilymph TMPA concentration. After a period of TMPA loading, a perilymph sample was aspirated and its TMPA content determined. Differences between the sample concentration and the measured TMPA time course during perilymph loading and sampling were analyzed using a finite element computer model for simulation of solute movements in the inner ear fluids. The experimental results were consistent with the aspirated fluid sample from the cochlea being replaced by CSF drawn into the perilymphatic space through the cochlear aqueduct. The dependence of perilymph sample purity on the location of sampling and on the volume withdrawn was quantified. These relationships are of value in the design and interpretation of experiments that utilize perilymph sampling.
我们对药物外淋巴动力学的理解很大程度上依赖于通过分析外淋巴样本获得的数据。尽管许多研究已经定性地证明外淋巴样本可能受到脑脊液(CSF)的污染,并且一些研究采用了特定方法来尽量减少样本的脑脊液污染,但许多其他研究未能考虑这种潜在假象对其测量结果的影响。在本研究中,我们试图使用离子标记物三甲基苯基铵(TMPA)来量化从豚鼠耳蜗底转采集的外淋巴样本的脑脊液污染程度。将TMPA溶液经圆窗膜灌注,同时将一个TMPA选择性电极密封在外淋巴间隙中,持续监测外淋巴中TMPA的浓度。在一段TMPA加载期后,抽取一份外淋巴样本并测定其TMPA含量。使用有限元计算机模型分析样本浓度与外淋巴加载和采样期间测得的TMPA时间进程之间的差异,以模拟内耳液中的溶质运动。实验结果与以下情况一致:从耳蜗抽取的液体样本被通过蜗水管吸入外淋巴间隙的脑脊液所替代。对外淋巴样本纯度对外淋巴采样位置和抽取体积的依赖性进行了量化。这些关系对于利用外淋巴采样的实验设计和结果解释具有重要价值。