Marshall, Robert J.

In studies on six experienced subjects lying supine, cardiac output and oxygen content of femoral venous blood were measured with the subject at rest, during the increase in muscle blood flow caused by intravenous infusion of epinephrine, during mild leg exercise, and during identical exercise combined with an infusion. The oxygen content of the blood from the exercising limb was much higher (average, 50%) during an infusion than when no infusion was given (average, 32%). The mean increase in cardiac output during the combined maneuver (8.2 liters/min) almost equaled the sum of the increases during the separate infusion (3.7 liters) and during exercise (4.7 liters). All individual studies showed approximately this same result. Thus, the additional blood supplied to the leg muscles by the infusion did not appear to be used for metabolic purposes during exercise. cardiac output; muscle blood flow Submitted on March 22, 1963

Changes in cardiac output, stroke volume, and systemic blood pressure have been correlated with changes in muscle blood flow during the periods of initial transient and subsequent sustamed vasodilatation during intravenous infusion of epinephrine. In the initial phase blood pressure decreased slightly; forearm blood flow increased by 308%, cardiac output by 50%, and stroke volume by 10%. During the sustained phase the systolic blood pressure increased; corresponding increases for the other measurements were 87, 47, and 25%, respectively. The lack of correlation between these changes in cardiac output and forearm blood flow suggests that in the transient phase vasodilatation does not occur simultaneously in all muscle groups. Stroke volume makes a greater contribution to the increased output during the sustained phase. Submitted on May 29, 1961

Cardiac output was measured simultaneously with blood flow in hand and forearm in eight healthy subjects before and during body heating. The heating was carried out by immersing the feet and legs in water at 44 C. and wrapping the body with blankets. After 50 min of heating the oral temperature had risen to between 99.5 and 100.8 F. The cardiac output had increased by 1.9—4.5 (mean 3.3) liters/min, mainly because of an increase in heart rate. The blood flow through the fingers increased rapidly to reach maximal values soon after heating started, whereas the forearm blood flow, like the cardiac output, increased gradually throughout the heating period. Since the increase in limb blood flow is confined to the skin vessels and since there is no evidence that flow to the internal organs is increased, the total increase in skin flow amounts on the average to 1.8 liters/m2/min. Submitted on June 2, 1961

Dilution curves were obtained by sampling from the aortic root or a carotid artery after injection of indicator dye into the pulmonary artery in five dogs at rest and during exercise. On four occasions a common sampling system was used; curves were recorded simultaneously and in parallel from a cuvette oximeter assembly with a slow dynamic response and from a phototube densitometer with a fast response. In the fifth study, separate slow and fast sampling systems were used interchangeably with the two detecting instruments. Values for cardiac output were similar with the two instruments; maximal divergence for any single observation was 9% from the line of identity. The aortic root is a favorable sampling site for such a comparison, since extrapolation of the dilution curves is usually unnecessary. Under these conditions measurement of cardiac output was not influenced by the dynamic response characteristics of the sampling-detecting-recording system. When mean transit times of the respective curves were corrected for instrumental delay, there was also satisfactory agreement in values for “central” blood volume. However, since the time correction for the densitometer is relatively small, it is the preferable instrument for this measurement. Submitted on October 24, 1960

Blood flow through the femoral artery was measured in 10 dogs; a bubble flowmeter was used in 5 and, in the other 5, an ultrasonic flowmeter was used. Rapid injections of 2 ml of 10–20% solution of NaCl caused a definite but transient reduction in flow, followed by a prolonged twofold to threefold increase. Similar effects were noted with other Na salts and also with 25–50% dextrose solution. The use of 25 and 50% solutions of urea caused only a prolonged increase in flow. Isotonic NaCl solution had little or no effect. Continuous infusions at 2.3 ml/min. of 10 and 20% solution of NaCl and 50% dextrose and urea solutions caused only doubled to tripled increase in flow which continued throughout infusion. The initial reduction in flow cannot be explained by reduction in perfusion pressure and may result from reversible hemagglutination in small vessels. The increase in flow is due to vasodilatation locally mediated, since it could not be accounted for by changes in perfusion pressure and was unchanged after denervation of the leg. The mechanism of the dilatation is uncertain, but since it occurs with salt-free hypertonic solutions it is not specific for sodium-containing salts.

The manner in which the administration of epinephrine, norepinephrine, isoproterenol, and atrophic modifies the cardiovascular response to exercise has been studied in 12 dogs. In control observations, exercise increased the cardiac output by 116 per cent, the heart rate by 102 per cent, and the stroke volume by 8 per cent. When epinephrine was infused during identical exercise, the cardiac output was similar; however, the stroke volume was increased by 50 per cent. During infusion of norepinephrine, the cardiac output was reduced by 11 per cent compared with that during control exercise, and the stroke volume was increased by 25 per cent. With isoproterenol, the cardiac output exceeded that during control exercise, but the stroke volume was unchanged. Prior to administration of atropine, the cardiac output at rest averaged 4.2 L. per minute. After injection of atropine, the cardiac output averaged 3.7 L. per minute, the heart rate increased from 121 to 249 beats per minute, and the stroke volume decreased from 35 to 15 ml. Before atropinization, the cardiac output, heart rate, and stroke volume during exercise were increased by 95, .90, and 2 per cent over the resting values; after atropinization, the corresponding increases were 110, 7, and 100 per cent. Thus, while cardiac output during exercise normally is regulated mainly by changes in the heart rate, the stroke volume may make a major contribution under other circumstances.

The effect of exercise on the pulmonary circulation was studied in a group of 6 intact dogs and in a second group of 4 subjected to ligation and division of the left pulmonary artery. Observations were made with the dogs standing and running on a horizontal treadmill up to the maximal speed they could maintain for periods of at least 2 minutes, usually 12 or 14 km./hr. Continuous records were made of the difference in pressure between the main pulmonary artery (PA) and a pulmonary-artery wedge (PAW) position. Cardiac output was determined by the indicator-dilution method, with injection of indocyanine (cardiogreen) dye into the main pulmonary artery and continuous sampling from the root of the aorta. The mean transit time of indicator betweell the pulmonary and aortic valves was obtained from the dilution curves, a correction being made for the transit time through the sampling apparatus. From these measurements the blood volume of the lungs and left heart chambers was derived. In the intact dogs, cardiac output increased approximately threefold from rest to severe exercise. There was an increase of only 12 per cent to 50 per cent in PA minus PAW pressure. Thus a continued fall occurred in pulmonary vascular resistance. The blood volume of the lungs and left heart of 3 intact dogs was measured. In 2 it did not change through the range of activity, and in the third the increase with maximal exercise was 18 per cent. The dogs with ligated left pulmonary artery also showed a threefold increase in output with severe exercise. Since the entire output passed through a single lung, the effect on the pulmonary vessels was comparable to that of a sixfold increase in output in a normal dog. Despite such large flows, in 3 of 4 dogs the difference between PA and PAW pressure rose only 37 per cent to 50 per cent. The volume of blood in the lungs and left heart was unchanged between rest and 8 km./hr., and at higher speeds showed a 0 per cent to about 20 per cent increase.

Measurements of stroke volume were made in dogs during graded exercise on a horizontal treadmill up to the maximal exercise which they could maintain for 2 to 3 minutes. Eleven series of experiments were performed on 7 dogs. The cardiac output was measured by the indicator-dilution technic and the heart rate was measured from the aortic pressure tracing. At all grades of exercise, there was little or no change in stroke volume. Even with severe exercise, when the cardiac output had increased from 1.5 to 3.5 (average, 2.4) times the values obtained with the dog standing at rest, the stroke volume showed less than 5 per cent change over resting values in 5 experiments on 4 dogs, while in the remainder the increases were 8, 11, 11, 14, 15, and 19 per cent. Thus, the increase in cardiac output in the untrained exercising dog is almost directly proportional to the increase in heart rate. This is in contrast to other situations, such as the combination of exercise with infusion of catecholamines, where an increase in stroke volume may make an important contribution to the increase in cardiac output.

The indicator-dilution method was used in the dog in an attempt to define the proportion of the "central" blood volume contained in the lung vessels. When injections were made into the pulmonary artery with sampling from the femoral artery only half or even less of the calculated blood volume could be accounted for by the lungs. When a venous injection site was used, the proportion in the lungs was reduced to a third or less. Thus when peripheral sites are used for the inscription of indicator-dilution curves few deductions can be made about either the actual volume or even relative changes in the volume of blood in the lungs.

Some of the factors that influence the contours and time components of indicator-dilution curves have been examined in dogs and man. These include the dynamic-response characteristics of the sampling-detecting-recording system, variations in the sampling site, quantity of blood and rate of blood flow between injection and sampling sites, vascular obstruction, and local and general alterations in peripheral blood flow. Any or all of these factors may be of importance in the interpretation of changes in indicator-dilution curves in patients with congenital or acquired heart disease.