Capillary Permeability of Heterogeneous Organs: A Parsimonious Interpretation of Indicator Diffusion Data

Calculations of capillary permeability of perfused organs from indicator diffusion data are reviewed, and reconsidered in terms of two kinds of organ heterogeneity of capillary extraction. 3. In the presence of realistic back-diffusion and recirculation of the indicator, the foregoing expression for PS is converted into a secure lower bound of the organ PS. Using data from four previously published studies of the brain and of the heart as examples, it is shown that this lower bound approaches and sometimes exceeds the widely differing PS values estimated by four existing methods based on more restrictive assumptions. In particular, PS estimates from the initial extraction (Eo method) fall below the lower bound in three of the four cases. 4.The new results are valid without restriction on the magnitudes of the extraction fractions, so that they provide legitimate PS estimates even for highly diffusible indicators. 5. Quantitative hypotheses needed for more complete modelling of indicator diffusion are reviewed, and elaborated in terms of both deterministic and probabilistic models.