  Objective: Interstitial fluid flow through vascular adventitia has been
disclosed recently. However, its kinetic pattern was unclear. Methods and
Results: We used histological and topographical identifications to observe ISF
flow along venous vessels in rabbits. By MRI in alive subjects, the inherent
ISF flow pathways in legs, abdomen and thorax were enhanced by paramagnetic
contrast from ankle dermis. By fluorescence stereomicroscopy and layer-by-layer
dissection after the rabbits were sacrificed, the perivascular and adventitial
connective tissues (PACT) along the saphenous veins and inferior vena cava were
found to be stained by sodium fluorescein from ankle dermis, which coincided
with the findings by MRI. By confocal microscopy and histological analysis, the
stained PACT pathways were verified to be the fibrous connective tissues and
consisted of longitudinally assembled fibers. By usages of nanoparticles and
surfactants, a PACT pathway was found to be accessible for a nanoparticle under
100nm and contain two parts: a tunica channel part and an absorptive part. In
real-time observations, the calculated velocity of a continuous ISF flow along
fibers of a PACT pathway was 3.6-15.6 mm/sec. Conclusion: These data further
revealed more kinetic features of a continuous ISF flow along vascular vessel.
A multiscale, multilayer, and multiform interstitial/interfacial fluid flow
throughout perivascular and adventitial connective tissues was suggested as one
of kinetic and dynamic mechanisms for ISF flow, which might be another
principal fluid dynamic pattern besides convective/vascular and diffusive
transport in biological system.
