Department of Bioengineering, University of Washington, Box 355061, Seattle, WA 98195-5061, USA.
Am J Physiol Lung Cell Mol Physiol. 2013 Jul 1;305(1):L42-55. doi: 10.1152/ajplung.00420.2012. Epub 2013 May 3.
A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution "bolus sweep" experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA. J Appl Physiol 51: 405-414, 1981; Rickaby DA, Dawson CA, and Linehan JH. J Appl Physiol 56: 1170-1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA. J Appl Physiol 57: 720-730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ~0.3 ml·g⁻¹·min⁻¹, low compared with the transporter-mediated maximum PS of 13 ml·g⁻¹·min⁻¹ (with Km = ~0.3 μM and Vmax = ~4 nmol·g⁻¹·min⁻¹). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T. Circ Res 39: 523-531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA. Ann Biomed Eng 15: 217-227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG. J Appl Physiol 66: 2328-2337, 1989) The identification and quantitation of the cleft pathway conductance from these studies affirms the importance of the cleft permeation.
构建了一个包含四个区域（毛细血管血浆、内皮细胞、细胞间质液和细胞）的多路径模型，以描述肺部中小溶质的血液-组织交换动力学，同时考虑到了局部血流异质性、细胞膜的通透性以及内皮细胞间隙的渗透性和细胞内反应。通过对 Rickaby 及其同事（Rickaby DA、Linehan JH、Bronikowski TA、Dawson CA。J Appl Physiol 51: 405-414, 1981；Rickaby DA、Dawson CA 和 Linehan JH。J Appl Physiol 56: 1170-1177, 1984）和 Malcorps 等人（Malcorps CM、Dawson CA、Linehan JH、Bronikowski TA、Rickaby DA、Herman AG、Will JA。J Appl Physiol 57: 720-730, 1984）的多指示剂稀释“推注冲洗”实验的血清素摄取数据进行了分析，以区分推注冲洗中的注入物中促进转运的血清素和被非示踪物血清素抑制的示踪剂转运，以及自由无抑制地通过裂孔渗透到细胞间质空间的情况。通过内皮细胞间隙的血清素渗透的表面积-渗透率乘积（PS）约为 0.3 ml·g⁻¹·min⁻¹，与转运蛋白介导的最大 PS（13 ml·g⁻¹·min⁻¹，Km=0.3 μM，Vmax=4 nmol·g⁻¹·min⁻¹）相比，这个值较低。从他们的多个数据集估算的内皮细胞转运蛋白的血清素 PS 值相似，并且仅通过同时考虑裂孔通透性对其进行适度影响。在这些用林格氏液灌注的肺中，裂孔 PS 的估计值小于具有正常红细胞压积的麻醉狗的一半（Yipintsoi T. Circ Res 39: 523-531, 1976），但与同一实验室后来观察到的无载体介导的被动转运相匹配（Dawson CA、Linehan JH、Rickaby DA、Bronikowski TA. Ann Biomed Eng 15: 217-227, 1987；Peeters FAM、Bronikowski TA、Dawson CA、Linehan JH、Bult H、Herman AG. J Appl Physiol 66: 2328-2337, 1989）。从这些研究中确定和量化裂孔途径的电导，证实了裂孔渗透的重要性。
