Restricted diffusion of CrEDTA and cyanocobalamine across the exchange vessels in rat hindquarters

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Abstract
The degree of diffusional restriction of skeletal muscle capillary walls to small solutes was estimated from the permeability surface area products (PS) of CrEDTA (MW = 341) and cyanocobalamine (MW = 1355), using computerized 'on-line' recordings of venous single injection indicator dilution curves. Experiments were performed on isolated perfused maximally vasodilated rat hindquarters during largely isogravimetric conditions and the arrangements allowed for measurements of capillary filtration coefficients (CFC). Extraction of tracer varied markedly as a function of transit time and, furthermore, PS increased with increasing flows, both these phenomena indicating tissue and flow heterogeneity. At maximal flows the disturbing influence of heterogeneity will be minimal and hence the diffusion capacities obtained by extrapolating PS area to infinite flows, so called PS tot values, were considered to give the best estimation of the 'true' capillary diffusion capacities. The value of PS tot was 12.9 +/- 0.5 for CrEDTA and 5.1 +/- 0.3 ml min-1 per 100 g for vitamin B12. The calculated PS tot ratio of 2.59 +/- 0.11 indicates restricted diffusion through equivalent pores of radius 53 A, whereas the ratio of the free diffusion coefficients for these solutes is 1.79. Using PS peak for the calculations (totally neglecting heterogeneity) the pore radius was, however, markedly overestimated. Thus, for a PS-ratio of 1.89 +/- 0.04 for CrEDTA vs. B12 an equivalent pore radius of 300 A was calculated. Also, using PS area (only partly correcting for heterogeneity) overestimated the pore radius (70 A) from a mean PS-ratio of 2.33 +/- 0.05. It was concluded that the equivalent pore radius in rat hindquarter microvascular walls is 53 A or even smaller in essential agreement with data from osmotic transient experiments in the same preparation (r approximately 40 A).