Layers of interstitial fluid flow along a “slit-shaped” vascular adventitia

Abstract

Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6–15.6 mm/s. These data revealed that a PACT pathway was a “slit-shaped” porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical “gel pump” is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.

概要

目的

本文旨在进一步研究沿血管外膜组织液流动的运动学特征。

创新点

(1)静脉血管外膜及其周围结缔组织中的组织液连续流动至少存在两种空间:血管外膜中沿纤维表面空间的连续流动,血管外膜及其被膜之间的连续流动;(2)静脉血管外膜及其周围结缔组织中的组织液流动包含两部分:传输通道(transport channel)和吸收区(absorptive part);(3)静脉血管外膜中的组织液流动的空隙大小约在100 nm以下;(4)表面活性剂对静脉血管外膜及其周围结缔组织中的组织液流动模式具有显著的影响,包括降低组织液的流量、抑制外膜吸收区对于组织液的吸收、抑制外膜通道中的组织液流动等;(5)提出静脉血管外膜及其周围结缔组织中的组织液流动的动力机制假说:凝胶泵假说;(6)静脉血管内的血液流动呈螺旋状,提示管腔内很可能存在类似“枪膛线”结构。

方法

利用磁共振成像、体视荧光成像等技术,采用分层解剖法、组织学、电镜和共聚焦等分析方法,在动物实验中观察不同种类示踪剂所显示的组织液沿血管外膜及其周围结缔组织中的流动过程,包括磁共振对比剂、荧光素钠、不同粒径的金纳米颗粒、带不同电荷的表面活性剂等。

结论

血管外膜及其周围结缔组织是一种“缝隙样”生物多孔材料,包括传输通道和吸收区两部分;表面活性剂的影响提示外膜的多层组织液流动与界面张力有关;根据界面张力和界面相互作用提出了“凝胶泵”假说;这些实验发现对深入理解血管外膜中组织液流动的生理学和病理生理学功能,以及全身结缔组织网络中的“界面液体流动”提供了新的思路。