Whole-body microvascular permeability of small molecules in man: clinical aspects, basic concepts and limitations of the single injection technique

Abstract

In order to estimate whole-body permeability-surface area (PS) product, the initial slope of the plasma disappearance curve was determined after simultaneous i.v. injection of ²⁴Na⁺ (mol.wt 24) and ⁵¹ Cr-EDTA (mol.wt 342). Twelve subjects were studied. Plasma volume (PV) was measured by the indicator dilution method, and the mean transit time of tracer in plasma was calculated as the reciprocal value of the initial fractional disappearance (initial slope). Estimated whole-body PS product (=PV/) of ²⁴Na⁺ (median 2.72, range 1.51–3.80 ml/min × 100 g body weight) was significantly higher than that of ⁵¹Cr-EDTA (median 2.16, range 1.59–2.84 ml/min × 100 g, p<0.005). The PS_24na :PS_51Cr-EDTA ratio was median 1.26 (range 0.91–1.44), and this value is significantly lower than the ratio between the free aqueous diffusion coefficients (D_24Na:D_51Cr-EDTA=2.54, p<0.005) but also significantly above unity p<0.005). The ratio between PS_51Cr-eDTA and earlier estimates of whole-body PS product of polyfructosan (mol.wt 3000) was close to the ratio of their free diffusion coefficients. The results indicate that whole-body PS product may be estimated from the initial slope of the plasma disappearance curve of a tracer, but mixing problems and flow-limited transport, as indicated by a PS ratio below that of the free diffusion coefficients, may be difficult to overcome, especially when using tracers of a low molecular weight.

Key Words:

• capillary diffusion coefficient
• permeability-surface area (PS) product
• plasma disappearance curves