Upper and lower bounds on capillary permeability ratios of Cr‐EDTA to cyanocobalamine in rat hindquarters

Abstract

The single injection indicator dilution technique, often used for assessing capillary permeability, was employed for estimations of the equivalent pore radius of skeletal muscle microvessels according to the theory of restricted diffusion. There are, however, certain important sources of error that must be considered in order to allow conclusions regarding the degree of restricted diffusion. In this study, we have recalculated previously published data in order to minimize the effect of heterogeneity of the second kind, i.e. a transit-time dependence of the fractional extraction values. The method used makes it possible to calculate reliable intervals of confidence for the permeability surface area products, and hence for the permeability surface area product-ratios (and equivalent pore radius), taking into account the maximal theoretical impact of back diffusion on measured extraction data. After correction for transit-time dependent effects of heterogeneity, the permeability surface area product-ratio of Cr-EDTA to cyanocobalamin (vit. B12) from 48 measurements in eight rats was found to have a theoretical 'upper bound' of 2.63 +/- 0.06 and a lower bound of 2.10 +/- 0.07, corresponding to an equivalent pore radius of 60 to 109 A. This minimum pore radius estimate was even further reduced by corrections for plasma flow dependent reductions in overall extraction fraction (heterogeneity of the first kind) to 45 A, whereas the upper bound on pore radius was reduced to 60 A. These data strongly support the presence of marked restricted diffusion of small solutes in the maximally vasodilated rat hindquarter microvasculature.