The permeability coefficients of dog red cell membrane to tritiated water and to a series of [1 4 C]amides have been deduced from bulk diffusion measurements through a "tissue" composed of packed red cells. Red cells were packed by centrifugation inside polyethylene tubing. The red cell column was pulsed at one end with radiolabeled solute and diffusion was allowed to proceed for several hours. The distribution of radioactivity along the red cell column was measured by sequential slicing and counting, and the diffusion coefficient was determined by a simple plotting technique, assuming a one-dimensional diffusional model. In order to derive the red cell membrane permeability coefficient from the bulk diffusion coefficient, the red cells were assumed to be packed in a regular manner approximating closely spaced parallelepipeds. The local steady-state diffusional flux was idealized as a one-dimensional intracellular pathway in parallel with a one-dimensional extracellular pathway with solute exchange occurring within the series pathway and between the pathways. The diffusion coefficients in the intracellular and extracellular pathways were estimated from bulk diffusion measurements through concentrated hemoglobin solutions and plasma, respectively; while the volume of the extracellular pathway was determined using radiolabeled sucrose. The membrane permeability coefficients were in satisfactory agreement with the data of Sha'afi, R. I., C. M. Gary-Bobo, and A. K. Solomon (1971. J. Gen. Physiol. 58:238) obtained by a rapid-reaction technique. The method is simple and particularly well suited for rapidly permeating solutes.
A B S T R A C T Five patients received cholesterol7a-3H intravenously during control periods. Specific activity of total serum cholesterol was determined serially during the 1st wk and weekly thereafter. 28-59 wk after the injection of the tracer, when no further radioactivity could be detected in serum cholesterol, 2 g of oral neomycin was given daily to four patients for the remainder of the experiment. Average total serum cholesterol concentrations were reduced by 20, 21, 26, and 29%, respectively, in these subjects. The fifth patient, given placebo, had no change in serum cholesterol. After a period of 12-26 wk of medication the intravenous injection of cholesterol7a-3H was repeated, and while neomycin or placebo administration was continued, serum cholesterol specific activity was again determined serially during the 1st wk and weekly thereafter for 23-42 wk. The data were subjected to a twocompartment analysis. During the administration of neomycin, half-times of the cholesterol radioactivity decay curves were decreased in two patients and remained unchanged in two subjects.
A model for interpretation of extravascular indicator dilution experiments is proposed, in which the indicator is assumed to enter the blood-tissue exchange region through vascular sources, to equilibrate instantaneously and locally between blood and tissue at the capillary-cell level, and, while maintaining this local equilibration, to be transported to vascular sinks by simultaneous diffusion and convection at a more macroscopic distance level. The model has the mathematical form of the time-dependent Fick diffusion equation to which a convection term was added. The model contains as opposite limiting cases the washout-type models and a recently proposed delayed wave model of the indicator dilution process. The various features of the extravascular indicator outflow pattern-appearance time, modal time, semi-log downslope, and dispersion about the mean-are described in terms of two parameters: (1) a diffusion parameter, square of source-to-sink distance divided by diffusion coefficient of the indicator in the tissue; (2) a convection parameter, the blood flow divided by steady-state solubility volume of distribution of the indicator in the tissue. In contrast to the preceding opposite limiting cases, the present model accounts plausibly for extravascular indicator experiments in dog kidney.
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