Relationship of plasma time-concentration curves to plasma volume, interstitial fluid volume, vascular permeability and renal clearance of substances confined to the extracellular fluid

American Federation for Clinical Research measured. The urine volumes during water loading were essentially equivalent to the infusion rate in all but two patients. The average time required to attain peak diuresis, ninety minutes, was similar to that previously reported for cirrhotic patients and normal subjects given smaller intravenous water loads. The degree and duration of nicotine antidiuresis were equivalent to those following 10 to 20 milliunits of pitressin. Urinary electrolyte excretion rate did not change significantly, despite decreases in serum concentrations during water loading. Except for slight changes associated with urine flow, creatinine clearances remained constant. These data suggest that tolerance to intravenous water loads in patients with liver disease is unimpaired. The equivalent duration of nicotine and pitressin antidiuresis points to a similar rate of inactivation of antidiuretic substance of endogenous or exogenous origin in cirrhotic patients. REI~ATIONSHIPOF PLASMATIME-CONCENTRATION CURVESTO PLASMAVOLUME, INTERSTITIALFLUID VOWME, VASCWAR PERMEABILITYAND RENAL CI.EARANCE OF SUBSTANCESCONFINED TO THE EXTRACELLULAR FLUID. Mi. R. Best, M.D. (From the U. S. Army Medical Nutrition Lab., Chicago, Ill.) The exact contour of time curves describing plasma concentration, interstitial concentration and total quantity in the body following a single intravenous injection of an extracellularly distributed substance were studied through a simple hydraulic analogy. The volume of each body fluid compartment was represented by the cross sectional areaof a cylindricalcontainer; the concentration of substance in that compartment by the height of water contained; and the amount of substance present by the volume of water. Vascular permeability and renal clearance were represented by the resistance to water flow in horizontal spouts at the bottom of each container. Assuming a uniform vascular permeability and instantaneous mixing within each compartment, all factors contributing to final concentration curves can be precisely studied with this analogy and translated into the biologic system. Thus changing plasma concentrations are described as the sum of two exponential curves. The characteristics of these curves are intricately related to dose of substance, plasma volume, interstitial volume, vascular permeability and renal clearance. A fixed ratio of plasma to interstitial concentrations is ultiAPRIL,

1953

mately achieved and is defined by these factors. The hydraulic analogy may be further broadened to consider multiple vascular areas having different permeabilities, as probably occurs in vivo. OXYGEN AND GLUCOSE CONSUMPTION 01: THE LIVER IN MAN. H. R. Bierman, M.D., L. P. White, M.D.,* and K. H. Kelly, M.D. (From the National Cancer Institute, National Institutes of Health and Univ. of California School of Medicine, San Francisco, Calif.) Portal venous blood was obtained from thirty patients with cancer by direct transhcpatic venepuncture through the intact abdominal wall. The oxygen and glucose content of portal venous blood were compared with simultanrously drawn arterial and hepatic venous blood. The oxygen saturation of portal venous blood averaged 69.7 per cent (range 59.2 to 80.5 per cent) or approximately midway between the hepatic venous 55.1 per cent (range 38.2 to 63.0 per cent) and arterial blood 91.7 per cent (range 87.7 to 96.0 per cent). The glucose content of portal venous blood averaged 17 tng. per cent above the peripheral venous or arterial content in thirteen cases, with a range of 7 to 55 mg. per cent. In six patients the glucose content was equal to or below that of thr peripheral venous or arterial blood. In five cases the portal content was greater than that in the hepatic blood, averaging 13 mg. per cent (range 10 to 22 mg. per cent) ahove the hepatic vein: in four patients there was no significant difference. In two patients the hepatic vein glucose content was greater than that in the. portal blood, by 9 mg. per cent and 26 mg. per cent, respectively. By determining hepatic blood flow a differentiation of glucose and oxygen consumption of the portal organs and the liver is now possible. Transhepatic portal venepuncture in man is technically feasible as a bedside procrdure with little risk or discomfort and affords a direct clinical approach to the portal venous system. MOBILITY OF HUMAN PLATEIXTS IN A MICROELECTROPHORESIS CELL. F. S. Bigrlow, .U.D. und J. F. Desforges, M.D. (From the Thorndike Memorial Lab., Boston City Hospital and the Harvard Medical School, Boston, Mass. ) The surface charge of human platelets has been investigated by microscopic observation of electrophoretic mobility. On application of direct current (5 milliamperes)? platelets mi-