Marshall, Hiram W.

Determinations of pressure, blood flows, and calculated pulmonary vascular resistance were made prior to and during acute individual occlusion of the right and left main branches of the pulmonary artery in random sequence in eight anesthetized, closed-chest dogs witn chronic atrial septal defects. Similar observations were made with occlusion of only the left pulmonary artery in three additional dogs. Obstruction of the pulmonary artery to one lung was immediately followed by a rise in systolic pressure in the right ventricle and pulmonary artery proximal to the obstruction, from an average normal value of 33.1 mm. Hg to an average value of 40.9 mm. Hg (range 32 to 47). This change was not associated with demonstrable systematic effects on right atrial or systemic arterial pressure or on the systemic blood flow. As would be expected, the average calculated ratio of pressure to flow (vascular resistance) across the unoccluded lung was elevated during the obstruction. The resistance value during the occlusion, however, was less than the estimated pressure/flow ratio for this same lung, based on the measurements made prior to the occlusion. This apparent effective decrease in vascular resistance of the unoccluded lung is probably related to dilation of the pulmonary vessels as a result of an increase in intravascular pressure caused by the sudden removal of approximately half of the pulmonary vasculature from the circulation. In spite of the elevation in right ventricular systolic pressure, occlusion of the left pulmonary artery was associated with a slight increase in pulmonary blood flow and a definite increase in the magnitude of the left-to-right shunt across the atrial septal defect, whereas no systematic effects were obtained during obstruction of the right branch in association with the same approximate levels of right ventricular systolic pressure. These data are regarded as further evidence that the preferential shunting of blood from the right lung in the presence of an atrial septal defect of the secundum type is primarily due to the anatomical relation between the opening of these vessels into the left atrium and the position of the defect in the atrial septum. Furthermore, they emphasize the importance of dynamic factors, related to the manner, site, and direction in which the pulmonary venous blood drains into the left atrium, as important determinants of the left-to-right shunt via such defects.

Systemic and pulmonary blood flows and pressures were determined in anesthetized closed-chest dogs with chronic atrial septal defects and in dogs with intact cardiac septa. In the former animals, graded obstruction of the main pulmonary artery associated with right ventricular systolic pressures of more than 80 mm. Hg was produced without evidence of failure of the right side of the heart. A considerable decrease in the magnitude of the left-to-right shunts and an increase in the size of the right-to-left shunts occurred; these changes were associated with only minor changes in filling pressure of the right ventricle, and systematic changes in systemic arterial pressure did not appear. Analysis of right atrial pressure pulses suggested the development of an increased force of contraction of the right atrium and no evidence of tricuspid regurgitation under these circumstances. In contrast, partial obstruction of the main pulmonary artery in the dogs with intact cardiac septa, so as to increase the right ventricular systolic pressure to more than 60 mm. ITg, was associated with pronounced increases in mean right atrial pressure and striking decreases in cardiac output and systemic arterial pressure. The pressure recordings from the right atrium and indicator-dilution curves demonstrated the development of significant tricuspid regurgitation. The deterioration of right ventricular function in dogs with intact cardiac septa appears to be related to overdistention of the right ventricle and possibly also to a disproportionate reduction in coronary blood flow to the myocardium caused by a decrease in systemic arterial pressure and the concomitant increase in resistance to coronary venous drainage from the right side of the heart due to the increased right atrial and right ventricular pressures. It is concluded that under the conditions of these studies, an atrial septal defect provides a considerable increase in resistance to the heinodynamic effects associated with right ventricular hypertension caused by acute partial obstruction of the main pulmonary artery. The possible duration of this beneficial effect beyond the 33 to 160 minutes of observation in these studies has not been explored.

The constant-rate-injection, indicator-dilution technic was used to determine thoracic aortic blood flow before, during, and after five minutes of single-leg exercise (bicycle ergometer) in five healthy male subjects in the supine position. Resistance to blood flow in the lower body and mean aortic pressure decreased immediately at the onset of exercise, at the same time that thoracic aortic blood flow and heart rate increased. There was a further slow rise of heart rate, mean aortic pressure, and thoracic aortic blood flow along with a decrease of lower body resistance until fairly stable levels were reached after five minutes of exercise. After five and ten minutes' rest all values tended to return toward those observed in the control state. These data are consistent with the concept that baroreceptor activity may play an important part in the early cardiovascular responses to exercise in man. Most of the cardiovascular response to this exercise occurred in the first 30 seconds.

The square-wave electromagnetic flowmeter was used to assess the upstream sampling dye-dilution technic for quantitating aortic regurgitation by simultaneous determinations of the regurgitant fraction by flowmeter, as given by the ratio of regurgitant volume to total stroke volume (RV/TSV) and the identical ratio of regurgitant flow to total forward flow (Q R /Q F ), and the regurgitant fraction by dye curve, as given by the ratio of the areas of the immediately appearing portion of the left ventricular curve to the area of the femoral artery dye curve (LV A /FA A ), after injection of indicator approximately 1 cm downstream to the aortic valve. A good correlation (r = 0.91) was found between these two independent methods which can be represented by the regression equation Q R /Q F = 0.82 (LV A /FA A ). This correlation indicates that the concept that the regurgitant fraction of indicator (LV A /FA A ) is proportionate to the regurgitant fraction of blood (RV/TSV) is valid. The observed systematic difference between flow-meter and dye-curve regurgitant fractions may be due to the fact that time-average rather than volume-average concentrations of the indicator are obtained by sampling of blood through eatheters. Two different and independent calibration technics were used to establish a calibration factor for converting recorded flowmeter deflections to volumetric units for measurement of rates and volumes of blood flow in the ascending aorta. The first technic involved simultaneous recording of dye-dilution curves and velocity pulses in the ascending aorta by the flowmeter before the production of aortic regurgitation. The second involved bidirectional perfusion of the isolated aorta at known rates of blood flow with simultaneous flowmeter recordings at the termination of each experiment. The data obtained validated the use of the flowmeter for measurements of total stroke volume and regurgitant stroke volume. The close correspondence between flowmeter recordings of the regurgitant flow and hydraulic estimates of regurgitant flow, based on the size of the defect in the aortic valve measured at necropsy and continuous records of the pressure gradient across the valve, also lent strong support to the validity of these measurements. The relationship Q R = Q S (Q R /Q F )/(1 - Q R /Q F ) can be used to estimate regurgitant flow from values of the regurgitant fraction (Q R /Q F ) and the systemic flow (Q S ). The mathematical relationship of the regurgitant fraction to regurgitant flow, determined by the dilution-curve technic, plus the variability obtained between simultaneous flowmeter and dilution-curve estimates of regurgitation, indicate that the error in the estimation of regurgitant flow by the dye-dilution technic is least for small-to-moderate degrees of regurgitation and increases progressively with the severe degrees of regurgitation associated with regurgitant fractions of greater than 0.6. On the basis of 231 simultaneous determinations by the indicator-dilution and flowmeter technics carried out in nine dogs, and assuming that the flowmeter values were uniformly correct, it was estimated that the standard deviation of the errors in measurement of regurgitant flow by the upstream sampling dye-dilution method in these experiments was 0.15 L per minute for regurgitant fractions below 0.6. and that this variability increased so that the standard deviation was 1.3 L per minute at regurgitant fraction levels of 0.9 to 1.0. The results of determinations carried out over a range of heart rates from 39 to 216 beats per minute indicate that the indicator-dilution method is applicable over a wide range of heart rates. The observed changes in aortic regurgitation with variation in heart rate correlated closely with the changes estimated by hydraulic equations based on the hydrodynamics of steady flow through an orifice. The increase in regurgitant stroke volume with increased duration of diastole at slow heart rates was disproportionately greater than the increase in total stroke volume, so that the effective forward (systemic) flow fell to extremely low levels at slow heart rates, particularly in dogs with large defects in the aortic valve. The applicability of the upstream sampling indicator-dilution technic to the detection and estimation of the severity of aortic regurgitation in human beings merits further study.

In dogs studied without thoracotomy the detection of immediately appearing indicator in the left ventricle following its injection approximately 1 cm downstream from the aortic valve can be used as a reliable index of the presence or absence of aortic regurgitation. With this type of injection and under the conditions of these experiments, the ratio of the area encompassed by the immediately appearing portion of the dilution curve recorded from the left ventricle to the area encompassed by the primary portion of the curve recorded at the femoral artery bears a close positive correlation (correlation coefficient: 0.9) to the severity of aortic regurgitation as estimated by back perfusion of the valve at necropsy. Within limitations, the position of the tip of the sampling catheter in the left ventricle in dogs with aortic regurgitation is not an important determinant of the amount of immediately appearing indicator detected in this chamber. Furthermore, although the amount of indicator detected in the left ventricle following injections of very short duration is time-dependent, if the duration of the injection is extended to cover the full systolic or diastolic phase of one heartbeat or continues over one or more heartbeats, the exact timing of this injection in relation to the cardiac cycle is not an important determinant of this variable. It is concluded that under these conditions the positive correlation established between the amount of immediately appearing dye detected in the left ventricle (expressed as the regurgitant fraction) and the severity of aortic regurgitation determined by back perfusion at necropsy can be used as a valid means of estimating the severity of aoritic regurgitation in dogs. The applicability of this indicator-dilution method to the study of clinical aortic reguragitation merits further study.

The effects of passive tilting on the circulatory pressures and on the magnitude of shunts across chronic atrial septal defects were studied in 11 dogs with closed chests. These determinations were performed with the dogs in four positions: 45-degree head-up, 45-degree head-down, right lateral decubitus, and left lateral decubitus. Control values were obtained with the animals in the supine horizontal position. The 45-degree head-up tilt position was associated with an increase in the magnitude of the right-to-left shunt detected after injections of indicator into the inferior vena cava, while change from supine to the 45-degree head-down tilt resulted in a decrease or disappearance of a pre-existing right-to-left shunt detected after similar injections. These effects on the right-to-left shunt were not demonstrable after injections of indicator into the superior vena cava, either during the head-up or head-down tilt, in spite of identical alterations in circulatory pressures. A significant interanimal correlation between the magnitude of the changes in systemic or right atrial pressures and the magnitude of the changes in right-to-left shunts could not be demonstrated. Passive changes in posture from supine to 45-degree head-up or head-down positions were not associated with demonstrable systematic effects on the magnitude of the left-to-right shunts. It is postulated that the descent of the heart and diaphragm during the head-up tilt results in a closer anatomical relation between the ostium of the inferior vena cava and the defect in the atrial septum and consequently an increase in the preferential shunting of inferior caval blood through this defect. In these animals, changing the body position from the supine to the right lateral decubitus position was consistently associated with an increase in the magnitude of the left-to-right shunts across the atrial septal defect and an increase in pulmonary blood flow. Since these animals have preferential shunting of blood from the right lung in the left-to-right direction, it is believed that the increase in blood flow through the dependent right lung is responsible for the observed increase in the left-to-right shunt. The left lateral decubitus position was not associated with appreciable effects on pulmonary blood flow or left-to-right shunting of blood across the atrial septal defect.

A method is described for detecting and quantitating small left-to-right shunts by recording continuously and simultaneously the changes in blood oxygen saturation at a systemic artery and at selected sites in the right heart chambers or great vessels produced by a few breaths of an inert gas such as helium or nitrogen. The advantages of this technic for detecting and quantitating left-to-right shunts are (1) the same instrument, namely, the cuvette oximeter, used to determine blood oxygen saturation and indicator-dilution curves in conjunction with routine diagnostic catheterization procedures, also is used to record the inert gas curves, (2) only one right heart catheter is needed, (3) the method is relatively simple, (4) the shunt can be quantitated, and (5) shunts of less than 10 per cent of pulmonary flow can be detected. It is concluded that the technic is of considerable practical value as a means of excluding the presence of or demonstrating and determining the magnitude of small left-to-right shunts.