An evaluation of radiosulfate for the determination of the volume of extracellular fluid in man and dogs.

Reasonably satisfactory methods have been developed for estimation of plasma volume (1) and total body water (2, 3) in normal subjects. On the other hand, no entirely satisfactory substance for estimating the volume of the extracellular fluid has as yet been found. It is not surprising that the material for this purpose should be more difficult to select, since, in order to have a volume of distribution equal to the extracellular fluid, it must be capable of passing through one membrane, the capillary wall, and yet be effectively excluded by the other, the cell wall. The use of large molecules such as inulin (4, 5) and sucrose (6, 7), which are excluded for the most part from body cells, is restricted by their slow rate of capillary diffusion, particularly in the case of inulin, which generally necessitates a constant infusion and limits the applicability of these methods in edematous states (8). Mannitol, which diffuses more rapidly (9, 10), suffers from the disadvantage of changing extracellular fluid in two ways in the process of measuring it, because the plasma concentration required for accurate analysis exerts an effective osmotic pressure which draws water from cells, thereby expanding extracellular fluid volume, at the same time that a mannitol diuresis is sweeping sodium chloride into the urine. Several ions which diffuse rapidly into the interstitial fluid have been employed for the measurement of extracellular volume, including bromide (11, 12), thiocyanate (7), thiosulfate (13, 14), ferrocyanide (15), and sulfate (7, 16). Bromide (17), thiocyanate (7, 18), and thiosulfate (13) all penetrate cells to a significant extent. Thiosul-