Many patients with circulatory failure either from hemorrhage or heart failure have anemia. In these patients, the cardiac output may be within normal limits and yet the circulation may be inadequate. The question immediately arises as to what is the effect of anemia on the requirements of the tissues of the body for blood. Before it can be determined whether a given patient with anemia has an adequate circulation, it is necessary to know how anemia per se affects the cardiovascular system and what level of cardiac output should be expected for a given hemoglobin concentration. Studies on the circulation were, therefore, carried out on patients with chronic anemia in whom the picture was not complicated by shock and by the marked decrease in total blood volume which are so often present in the acute anemia produced by hemorrhage. METHODSThe cardiac output was measured by the utilization of the direct Fick principle. Samples of mixed venous blood from the right atrium and measurements of atrial pressure were obtained from an inlying atrial catheter, introduced into the venous system through the antecubital vein (1, 2). The oxygen consumption was determined by the analysis of a 2-minute sample of expired air, using the method of Haldane. The metabolic rate was recorded as the percentage of deviation from the expected basal metabolism. The oxygen content of the blood was measured by the method of Van Slyke and Neill (3). A point 5 cm. below the 4th right costochondral junction was used as the reference point in reading the atrial pressure. The arterial pressure in the femoral artery was recorded optically by the method of Hamilton (4). The mean arterial pressure was measured by planimetric integration of the area beneath the tracing.

The determination of the cardiac output in man has usually been done by indirect methods. The demonstration (1) that mixed venous blood could be obtained by introducing a catheter into the right atrium and the later data (2), showing that this technique is simple and safe, have provided a new method for quantitative studies of the circulation in man. The purpose of this paper is to report the data obtained in the study of normal resting subjects by the catheter technique. Some of these persons were relaxed and quiet; others were nervous and apprehensive. METHODSPhysicians, medical students, hospital patients, and paid volunteers served as subjects. They had eaten no food since the evening meal 'on the night previously and they came to the laboratory at 7:30 a.m. After resting onehalf hour, the procedure was begun. Thirty to 90 minutes later, quantitative studies were made.The right atrium was catheterized via the median antecubital vein by the technique described by Cournand et al. (2 to 4). A slow drip of physiological saline solution was maintained through the catheter during the study. The necessity has been stressed (4) for having the tip of the catheter in the region of the tricuspid valve in order to obtain blood in which the streams from the superior and inferior cavae are fully mixed. Even with this precaution, a sample of mixed venous blood may not be obtained. In 3 subjects, blood from the atrium in the region of the tricuspid valve was found to have a very low oxygen content. Samples taken from the right ventricle or other parts of the atrium led to the conclusion that the catheter had entered the coronary sinus, or an aberrant hepatic vein emptying directly into the atrium.An inlying needle was placed in the femoral artery, which had previously been well novocainized. Oxygen consumption was measured by collecting ;expired air for 2-or 3-minute periods in a Douglas bag and analyzing its oxygen and carbon dioxide content by the method of Haldane. It was found necessary to bring in air from the outside of the building as the carbon dioxide content of the room air increased appreciably during the experiment. The metabolic rate was recorded as the percentage of deviation from the expected basal metabolism. The oxygen content of the mixed venous and arterial bloods was determined by the method of Van Slyke and Neill (5). The hemoglobin concentration of the blood was measured by diluting the blood with ammonia water and determining the intensity of the color by a photoelectric colorimeter. In the few instances where an arterial puncture was not done, blood from the atrium was saturated with oxygen and its oxygen capacity determined directly. The arterial oxygen content of the blood was then calculated on the assumption that the hemoglobin in the arterial blood was 95 per cent saturated with oxygen. It was not possible to calculate the oxygen carrying capacity of the blood from the concentration of the hemoglobin. Varying amounts of inactive hemoglobin were found in the blood. Similar observations have been ...

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The mechanisms by which the body compensates for a decrease in blood volume have not been thoroughly studied in man. All physicians are aware that from 500 to 1000 ml. of blood can be removed from a person of average size without producing any symptoms, if the body is horizontal. If the blood is removed rapidly, hemodilution plays little part in the immediate adjustment. Do the arterioles constrict, maintaining the arterial pressure at a normal level at the expense of blood flow to the tissues? Is the atrial pressure maintained at the normal level by venous constriction? Or is it possible that up to a certain point, the heart can function effectively with a falling atrial pressure so that the circulation can be maintained without either arteriolar or venous constriction in spite of a moderate decrease in blood volume?The purpose of this paper is to describe the changes in the circulation in normal subjects caused by moderate loss of blood from the body, either as the result of venesection or by pooling blood in the extremities through the application of venous tourniquets. During the experiments, acute circulatory collapse (primary shock) occurred in three instances and quantitative observations were made on the changes occurring in the circulation. METHODSMedical students, physicians, and paid volunteers served as subjects. They had not eaten for the preceding 12 hours and they rested in the horizontal position for at least 30 minutes before the experiment began.

Patients with myxedema present an unusual opportunity for studying the effect of lowered metabolism on organ blood flow and for observing the effect of changes in peripheral circulation on cardiac output. Studies of cerebral metabolism in myxedema are of interest to the physician because changes in cerebral metabolism may be of importance in understanding the alterations in mental status which occur with this disease (1-3). was recorded with a Hamilton manometer. The nitrous oxide technique for measuring cerebral blood flow has been previously described (4), and the modification in use in this laboratory of collecting simultaneous, continuous samples from the artery and internal jugular bulb, rather than five separate arterial and venous samples, has been reported elsewhere, together with our normal values (7). In the cerebral metabolism study, blood oxygen content was measured by the spectrophotometric method of Hickam and Frayser (8); in the cardiac output study, it was measured by the manometric method of Van Slyke (9). Blood glucose content was measured by Nelson's modification of Somogyi's method (10); in most instances, each arterial cerebral venous glucose difference represents an average of four such arteriovenous differences drawn during the procedure. The calculation of cerebral oxygen consumption, cerebral glucose consumption, and cerebral vascular resistance has been previously described (4, 7). Cerebral venous oxygen tension was not measured directly, but computed from the per cent oxygen saturation of the cerebral venous blood using a standard oxyhemoglobin dissociation curve drawn for pH 7.4. Mean arterial pressures in the cerebral metabolism study were calculated from the formula MP = diastolic pressure plus pulse pressure the readings 3 being obtained at one minute intervals by the standard auscultation procedure with the arm held at heart level. RESULTSCardiac output. The essential data are presented in detail in Table I. The patients with myxedema were compared with a group of normal subjects studied under the same laboratory circumstances (11). The mean decrease in cardiac index from nornal was 47 per cent, and the mean decrease in total oxygen consumption was 37 per cent. There was an excellent correlation between cardiac index and basal metabolic rate, the correlation coefficient (r) being 0.90. The apparent moderate increase in mixed arterial-venous oxygen difference proved not to be statistically significant. The two patients who were restudied after treatment showed sizable increases in both cardiac index and total oxygen consumption. 1139