GENTEX, a general multiscale model for in vivo tissue exchanges and intraorgan metabolism
GENTEX, a general multiscale model for in vivo tissue exchanges and intraorgan metabolism
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DOI：
10.1098/rsta.2006.1779
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发表时间：
2006-06-15
期刊：
影响因子：
5
通讯作者：
Bukowski, Thomas R.
中科院分区：
文献类型：
--
作者：
Bassingthwaighte, James B.;Raymond, Gary M.;Bukowski, Thomas R.
心肌毛细血管内壁的内皮细胞不仅阻碍血液溶质向收缩细胞的运输，而且还吸收和释放底物，与肌细胞竞争。渗透该屏障的溶质沿着毛细管表现出浓度梯度。本文介绍了一个通用模型 GENTEX，用于表征血液组织交换。 GENTEX 是血管网络的整个器官模型，提供器官内血流异质性，并解释红细胞、血浆、内皮细胞、间质空间和心肌细胞中的底物跨膜转运、结合和代谢。此处测试该模型，用于分析分离的 Krebs-Henseleit 灌注的非工作心脏中嘌呤核苷代谢的多种示踪指示剂稀释数据。它还用于分析局部心肌血流的 NMR 对比数据以及心脏受体动力学的正电子发射断层扫描研究。促进转运蛋白、结合位点和酶反应是非线性元件，允许底物之间以及代谢网络中多达五个底物-产物反应的反应序列之间的竞争。应用策略从结合惰性参考示踪剂的实验设计开始。为了估计内皮和肌膜渗透性表面积产物以及底物和产物的代谢，优化了模型解决方案以适应几分钟后在相同情况下注射的成对示踪剂注射（肌苷或腺苷，加上参考示踪剂）的数据。结果提供了对灌注良好的跳动兔心脏中核苷代谢的自洽描述，并说明了该模型同时拟合多个数据集的能力。
Endothelial cells lining myocardial capillaries not only impede transport of blood solutes to the contractile cells, but also take up and release substrates, competing with myocytes. Solutes permeating this barrier exhibit concentration gradients along the capillary. This paper introduces a generic model, GENTEX, to characterize blood-tissue exchanges. GENTEX is a whole organ model of the vascular network providing intraorgan flow heterogeneity and accounts for substrate transmembrane transport, binding and metabolism in erythrocytes, plasma, endothelial cells, interstitial space and cardiomyocytes. The model is tested here for the analysis of multiple tracer indicator dilution data on purine nucleoside metabolism in the isolated Krebs-Henseleit-perfused non-working hearts. It has been also used for analysing NMR contrast data for regional myocardial flows and for positron emission tomographic studies of cardiac receptor kinetics. The facilitating transporters, binding sites and enzymatic reactions are nonlinear elements and allow competition between substrates and a reaction sequence of up to five substrate-product reactions in a metabolic network. Strategies for application start with experiment designs incorporating inert reference tracers. For the estimation of endothelial and sarcolemmal permeability-surface area products and metabolism of the substrates and products, model solutions were optimized to fit the data from pairs of tracer injections (of either inosine or adenosine, plus the reference tracers) injected under the same circumstances a few minutes later. The results provide a self-consistent description of nucleoside metabolism in a beating well-perfused rabbit heart, and illustrate the power of the model to fit multiple datasets simultaneously.