Theory of Use of Indicators to Measure Blood Flow and Extracellular Volume and Calculation of Transcapillary Movement of Tracers

For indicators or tracers injected into the vascular system and sampled at some other portion of the vascular system, the indicator dilution curve supplies a measure of blood or plasma flow through the system even if the indicator is not confined to the blood vessels, providing only that it eventually all return to the circulation prior to the sampling site. Mean transit time of the indicator through the system multiplied by the measured flow determines the volume through which the indicator is distributed. This volume is independent of capillary permeability to the indicator if the indicator enters interstitial fluid at all. Of indicator coursing through the vascular system, the fraction crossing capillaries into interstitial fluid is inversely proportional to the mean transit time of the indicator across capillaries, through interstitial fluid and back into capillaries. The constant of proportionality is the ratio of interstitial fluid volume to plasma flow through the system. The fraction of a substance crossing capillary walls and returning can be calculated if the frequency function of transit times into, through and out of interstitial fluid can be measured. The equations cannot be solved if this frequency function is not measured. However, because this frequency function falls to zero much more slowly than other frequency functions through which tracer concentration is apt to be convoluted, capilary permeability may be estimated graphically. The graphic estimate applies even to substances that do not return completely to the vascular bed.