Warren and Stead's (1) contention that disturbed renal function secondary to a diminished cardiac output is responsible for the following series of events-salt and water retention, increased blood and extracellular fluid volume, rise in venous pressure, edema-seemed to offer a rational explanation for some of the clinically observed phenomena. We therefore initiated a series of studies on patients with chronic congestive heart failure, using the clearance techniques of Smith and associates (2), in order to evaluate the relationship between the decreased sodium excretion in heart failure (3, 4) and renal blood flow, to determine the nature of the disturbance in renal function and the relationship, if any, between the altered renal dynamics and sodium retention. We later attempted to define some of the variables involved in the tubular transfer system for sodium as it obtains in the normal and in the cardiac patient. Since our studies began, Merrill (5) reported that the renal plasma flow was reduced to as little as 20 per cent and the filtration rate to 33 per cent of normal in chronic congestive failure. We have been able to confirm his findings of a decreased sodium excretion rate due to a diminished load presented to the tubules for reabsorption, and not to enhanced tubular reabsorption as suggested by earlier workers (3). EXPERIMENTAL PROCEDUREPatients with advanced chronic congestive failure due predominantly to rheumatic heart disease were the subjects. All had variable amounts of edema at rest. Members of the resident house staff and patients without heart failure or renal disease served as controls.The subjects were brought to the laboratory in a postabsorptive state. Each patient was given 300 to 600 cc. of water about 30 to 60 minutes before the test period.' This study was aided by a grant from the Martha M. Hall Foundation and the Committee on Scientific Research of the American Medical Association.2 Martha M. Hall Foundation Fellow in Medicine.Five controls were maintained on a special cardiac saltpoor diet (about 1.3 grams of sodium chloride daily), for 4 to 5 days before the studies were made. Most of the patients with congestive heart failure were maintained on the same diet (strict metabolic control was not attempted) and, in addition, all were taking digitalis.

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The inadequate cardiac output of chronic congestive heart failure is accompanied by a general increase in peripheral resistance-reflected by the maintenance of normal blood pressure-and an even more marked renal vasoconstriction, which results in a disproportionate decrease in renal blood flow. Neurogenic factors seem to be excluded as the major reason for the renal ischemia, since presumptive functional denervation by high spinal anesthesia (1) does not affect the vasoconstriction. Merrill's (2) demonstration of an increased concentration of renin in the renal venous blood of congestive failure patients suggests the possible role of this humoral factor in the renal and peripheral vascular adjustments of heart failure.We have directed our attention to a newly described vasotropic system consisting of the renal vasoexcitor, VEM, and the hepatic vasodepressor, VDM, whose vascular effects are such as to suggest that they constitute a homeostatic regulatory mechanism for the peripheral circulation (3). VEM has been shown (4) to be regularly released in vivo from kidneys whose blood flow has been reduced by partial clamping of the renal artery, or after acute ischemia; and to be produced by kidney cortex in vitro under conditions of hypoxia.

One of the effects of a decreased cardiac output in chronic congestive heart failure is a disproportionate decrease in the renal blood flow. We have calculated the renal fraction of the cardiac output to be reduced to about two-fifths of normal and have shown that there is marked efferent arteriolar constriction with increased intraglomerular filtration pressure in congestive heart failure (1). Although Merrill and co-workers (2) have demonstrated that renin is present in increased amounts in the renal venous blood of some patients with congestive failure, we wondered if renal vasoconstriction might also result from neurogenic stimulation when the cardiac output falls; in which case, hyperemia should be produced by blocking the reflex pathways. In the present study the interruption of the autonomic vasoconstrictor path-.ways was effected by means of high spinal anesthesia. As will be seen from the results obtained in these experiments, renal hyperemia does not occur in response to the abolition of sympathetic vasoconstrictor impulses. METHODSFourteen patients with varying degrees of congestive heart failure were the subjects. They were examined in the post-absorptive state employing the clearance of mannitol (or sodium thiosulfate in two instances) as a measure of glomerular filtration rate, and the clearance of p-aminohippuric acid8 as a measure of effective renal plasma flow as described in a previous report (1).After and L 4. Metycaine d,1-3-Benzoxy-1-(2-methylpiperidino) propane Hydrochloride (120-150 mg.) mixed with equal parts of spinal fluid was the anesthetic agent. Procaine was not used because it has an amino group in the para position of the benzene nucleus and would result in falsely high values for p-aminohippurate (3). Moreover, a longer acting anesthetic agent was desirable. After the metycaine was injected rapidly, the patient was placed in the prone position with the pelvis tilted at an angle of -10 to -15 degrees. This position was maintained for about 10 to 20 minutes after which the patient was turned flat on his back. In two instances, because of the patient's severe dyspnea and orthopnea, the lumbar puncture was made in the upright position. In two other cases, because of unsatisfactory ascent of the anesthesia, a second injection of metycaine was necessary before the test periods were started. The test clearance periods were started after the highest level of sensory anesthesia was reached which was usually between 25 and 40 minutes after spinal injection. In several instances when the anesthesia reached the first thoracic segment and there was almost complete intercostal paralysis, oxygen was administered. Artificial respiration was available, but was never required. Blood pressure was taken by auscultation of the brachial artery at frequent intervals during the control and anesthesia periods. The figures given in Table I are the means of several readings in each period. RESULTSThe maximal level of anesthesia was unsatisfactory in three patients, who consequently have been omitted from co...

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