Heterogeneity of interstitial fluid space demonstrated by simultaneous kinetic analysis of the distribution and elimination of inulin and gallamine

The kinetics of inulin and gallamine were studied after simultaneous i.v. injection in anesthetized dogs. The distribution of both compounds in extracellular fluid space was characterized by a three-compartment model in which the mean central compartment blood volume of 1.37 liters was identical with the expected value. The two peripheral compartments of the model appear to represent rapid and slow equilibrating interstitial fluid compartments. A mammillary model structure was selected in which intercompartmental clearance corresponds to transcapillary exchange. Previous studies indicate that inulin and smaller hydrophylic molecules diffuse across capillary walls at rates proportional to their respective free water diffusion coefficients. For the ratio of the transcapillary permeability coefficients of inulin and gallamine to equal their free water diffusion coefficient ratio of 5.34 ± 0.02 (±S.D.), it appears that the sum of blood flows to the fast and slow interstitial fluid compartments is less than cardiac output. When this assumption is made, blood flow to fast equilibrating interstitial fluid is estimated to be 39% of cardiac output, in agreement with previous measurements of splanchnic blood flow. This supports the hypothesis that the fast equilibrating interstitial fluid space is supplied by porous splanchnic capillaries that lack a continuous investment of basement membrane.