Direct measurement of interstitial convection and diffusion of albumin in normal and neoplastic tissues by fluorescence photobleaching

Abstract

Macromolecular transport through the interstitial space of a tissue occurs by convection and diffusion. The convective component of transport results from interstitial fluid flow. There have been no direct measurements of the magnitude or direction of interstitial fluid flow in tissues to date. Using fluorescence recovery after photobleaching, we have measured interstitial fluid velocities and the diffusion coefficient of bovine serum albumin in normal and neoplastic tissues grown in a thin, transparent window in the ear of a rabbit. A well-defined laser beam was focused on a region within the interstitium of the fluorescence-bathed tissue. A short pulse of laser irradiation extinguished the fluorescence emanating from this selected region. The recovery of fluorescence due to diffusion and convection within the medium was monitored and analyzed to yield values of the diffusion coefficient and the fluid velocity. The average fluid velocity was about 0.6 microns/s, and albumin diffusion coefficients were 5.8 +/- 1.3 x 10(-7) cm2/s and 6.3 +/- 1.9 x 10(-7) cm2/s in normal and neoplastic tissues, respectively. The interstitial fluid flow, in general, was directed into postcapillary venules. The results obtained in this study should provide the impetus for further investigation into the diffusion and convection in various tissues under normal and pathological conditions.