Stenken J A, Holunga D M, Decker S A, Sun L
Department of Chemistry, Rensselaer Polytechnic Institute, 130 Cogswell Laboratories, 110 Eighth Street, Troy, New York 12180-3590, USA.
Anal Biochem. 2001 Mar;290(2):314-23. doi: 10.1006/abio.2000.4985.
Microdialysis sampling was performed to monitor localized metabolism in vivo and in vitro. A mathematical model that accounts for analyte mass transport during microdialysis sampling was used to predict metabolite concentrations in the microdialysis probe during localized metabolism experiments. The model predicts that metabolite concentrations obtained in the microdialysis probe are a function of different experimental parameters including membrane length, perfusion fluid flow rate, and sample diffusive and kinetic properties. Different microdialysis experimental parameters including membrane length and perfusion fluid flow rate were varied to affect substrate extraction efficiency (E(d)), or loss to the sample matrix, in vivo and in vitro. Local hepatic metabolism was studied in vivo in male Sprague-Dawley rats by infusing acetaminophen through the microdialysis probe. Acetaminophen sulfate concentrations increased linearly with respect to acetaminophen E(d) in contrast to modeling predictions. Xanthine oxidase was used as an in vitro model of localized metabolism. In vitro experimental results partially matched modeling predictions for 10-mm probes. These results suggest that monitoring local metabolism using microdialysis sampling is feasible. It is important to consider system parameters such as dialysis flow rate, membrane length, and sample properties because these factors will affect analyte concentrations obtained during local metabolism experiments.
进行微透析采样以监测体内和体外的局部代谢。使用一个考虑微透析采样过程中分析物质量传递的数学模型来预测局部代谢实验期间微透析探针中的代谢物浓度。该模型预测，在微透析探针中获得的代谢物浓度是不同实验参数的函数，这些参数包括膜长度、灌注液流速以及样品的扩散和动力学性质。改变包括膜长度和灌注液流速在内的不同微透析实验参数，以影响体内和体外的底物提取效率（E(d)）或向样品基质中的损失。通过微透析探针向雄性Sprague-Dawley大鼠体内输注对乙酰氨基酚来研究局部肝脏代谢。与模型预测相反，硫酸对乙酰氨基酚浓度相对于对乙酰氨基酚E(d)呈线性增加。黄嘌呤氧化酶被用作局部代谢的体外模型。体外实验结果与10毫米探针的模型预测部分匹配。这些结果表明，使用微透析采样监测局部代谢是可行的。考虑诸如透析流速、膜长度和样品性质等系统参数很重要，因为这些因素会影响局部代谢实验期间获得的分析物浓度。
