  Effects of mechanical stress on the permeability of vascular endothelium are
important to normal physiology and may be critical in the development of
atherosclerosis, where they can account for the patchy arterial distribution of
the disease. Such properties are frequently investigated in vitro. Here we
evaluate and use the hollow fibre bioreactor for this purpose; in this system,
endothelial cells form a confluent monolayer lining numerous plastic
capillaries with porous walls, contained in a cartridge. The capillaries were
perfused with a near-aortic waveform by an external pump, and permeability was
assessed by the movement of rhodamine-labelled albumin from the intracapillary
space to the extracapillary space. Confluence and quiescence of the cells was
confirmed by electron microscopy and measurements of glucose consumption and
permeability. The system was able to detect previously established influences
on permeability: tracer transport was increased by acute application of shear
stress and decreased by chronic shear stress compared to a static control, and
was increased by thrombin or an NO synthase inhibitor under chronic shear.
Increasing viscosity by addition of xanthan gum reduced permeability under both
acute and chronic shear. Addition of damping chambers to reduce flow
pulsatility increased permeability. Modifying the cartridge to allow chronic
convection across the monolayer increased effective permeability more than
could be explained the addition of convective transport alone, indicating that
it caused an increase in permeability. The off-the-shelf hollow fibre
bioreactor provides an excellent system for investigating the biomechanics of
endothelial permeability and its potential is increased by simple
modifications.
