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While many contributions have been made to the study of heart failure, the basic factor initiating the chain of events leading to edema formation in that condition remains unidentified. It is hoped that this report will present evidence which may prove useful in elucidating the problem. METHODSAll renal and circulatory studies to be reported were done on cardiac patients. Twenty-one patients were in heart failure at the time of the observations, while 18 were compensated cardiacs. In ten cases, studies were made in the same individual during failure and again after compensation had been restored. Patients were treated with digitalis, diuretics, bed-rest, and a low salt diet which, in actual ward experience, has not produced a very rigid restriction of sodium. Some patients had been on maintenance doses of digitalis prior to admission to the hospital. In these cases, digitalis was continued while other medication was withheld until initial studies were completed. When compensation was restored, as indicated by reduction of dyspnea and edema and maintenance of steady weight, all diuretic medication was withheld for at least 48 hours (in most cases for a much longer time), and the determinations were repeated.The cardiac output was determined by the Fick principle, utilizing the technique of right heart catheterization (1). This involved estimation of arterial and mixed venous blood oxygen content, and oxygen consumption. From the oxygen content of arterial (A) and venous (V) blood, the approximate oxygen saturation of the mixed venous blood was calculated from the relation V/A X 100. This tacitly assumes complete arterial saturation-which is near enough the truth for our purposes. Intracardiac pressures were measured by an optical manometer (2). Blood volume was measured with the dye T-1824 (3). The method used differed from that most frequently described in that the relation between dye dilution and optical density (at 625 tnm as measured in the Beckman spectrophotometer) was determined directly in the blood of the subject of each experiment. Standards were made up by diluting known amounts of the injected dye solution in whole blood, and the blood volume was calculated from these measurements, as compared with 1 This investigation was aided by a grant from the Life Insurance Medical Research Fund. the optical density of a sample drawn ten minutes after dye injection. This procedure avoids the controversial errors inherent in the centrifuge hematocrit. Plasma volumes were not measured, because these are less constant than blood volume since they vary inversely with cell volume. Plasma volumes are a less direct measure of the fluid which distends the vascular tree and brings about some of the signs of congestive failure, than are blood volumes. The thiocyanate space was estimated by the method described by Crandall and Anderson (4) and modified by Gregersen and Stewart (5). Glomerular filtration rate was measured by the sodium thiosulfate clearance (6). Sodium was determined by the method of Bradbury (7). Since th...

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