Swan, H.J.C.

Data on hemodynamic findings in 19 infants and children with ventricular septal defect are presented. The ages of these patients ranged from 3 months to 14 years. Significant elevation of pulmonary arterial pressure was found in 17 of the 19 patients studied. Left-to-right shunts, at times of large magnitude, were found in all these patients. However, right-to-left shunts accounting for up to 50 per cent of systemic flow were also obtained, even in young patients. A history suggestive of cardiac failure was obtained in seven patients. Cyanosis was constant in one patient and was found intermittently in three others. A systolic murmur was heard in most cases in the third or fourth intercostal space. In four additional patients a diastolic murmur was also identified. The electrocardiogram provided valuable information, which correlated with the relationship of pulmonary and systemic arterial resistances, the status of intracardiac shunting of blood, and the total pulmonary blood flow. These factors are considered to be of paramount importance in selection of patients for the operative closure of ventricular septal defect. It has been demonstrated that the hemodynamic status of the patient may be difficult to assess at the time of cardiac catheterization because of the unpredictable effect of anesthesia on ventilation. The use of dye-dilution curves in the diagnosis and evaluation of both right-to-left and left-to-right shunts is a vital factor in the adequate assessment of the patients from the hemodynamic standpoint.

Right ventricular hypertrophy was produced in normal dogs: in six by means of pressure overload (pulmonary artery banding) and in six by means of volume overload (systemic arteriovenous fistula). A greater degree of hypertrophy resulted from the latter procedure. Right ventricular hypertrophy due to chronic pressure overload causes a greater degree of infundibular constriction and much higher pressure gradient than in normal animals or in animals with volume overload. Infundibular pressure gradients associated with severe hypertrophy due to volume overload are not significantly greater than those observed in normal dogs. Infundibular gradients are dominantly related to narrowing of the outflow tract.

In each of 12 mongrel dogs, data for end-diastolic volume, end-systolic volume, and stroke volume of the left ventricle were obtained by two independent methods: the indicator dilution method and a radiographic method. While the values for stroke volume showed good agreement between the two methods, a significant and directionally constant difference was found between values for end-diastolic volume and end-systolic volume calculated by the two different methods. This was observed in dogs with fast heart rates (exceeding 150 beats/min), as well as in dogs with heart rates of about 100 beats/min. The findings strongly suggest that a fundamental error is present in estimations of volume based on the washout of an indicator dye.

5-Hydroxytryptamine (serotonin) was infused into anesthetized dogs at a rate of 20 µg/kg/min. In nine sets of observations on three dogs the increase in the difference of pressure between the pulmonary artery and the left atrium, which averaged 55%, consistently exceeded the increase in pulmonary blood flow, which averaged 16%. 5-HT therefore is a potent constrictor of pulmonary vessels, even in small concentrations. No changes in the pulmonary-artery wedge and pulmonary-vein pressures were detected during the infusions of 5-HT, nor was there any change in the volume of blood between the pulmonary artery and the root of the aorta. With this dose of 5-HT the principal site of the increased resistance to flow through the lungs appeared to be in the precapillary vessels. In the isolated perfused lung, moderate constriction of pulmonary veins also was produced by large doses of 5-HT.

1. In the anesthetized dog, end-diastolic, end-systolic and stroke volumes for the left ventricle have been calculated according to the method of Holt from dilution curves recorded at the aortic root. For heart rates of less than 120 beats per minute, the catheterdensitometer systems used gave 90 to 95 per cent of the true concentration in the aortic root at the end of diastole. 2. Average volumes of 2.96, 1.63 and 1.33 ml./Kg. of body weight were calculated for each of these parameters. The interindividual and intraindividual variations about these means amounted to ± 30 to 50 per cent. 3. In approximately 15 per cent of the dilution curves the concentration of dye in the aortic root during early systole (phase of maximal ejection) showed a transient, markedly low value compared with that of the end of diastole. This can be explained only on the basis of the preferential ejection from the heart in early systole of the undyed, newly entering blood from the left atrium, which had mixed poorly with the residual volume of the ventricle. Qualitative inspection of cineangiograms confirmed this impression and demonstrated that a residuum of contrast medium failed to mix with the incoming blood from the left atrium. 4. In addition, there is evidence for the possibility of overestiination of stroke volumes from dilution curves recorded immediately proximal to the injection chamber. 5. Incomplete mixing of the left artial blood with the residual volume of the ventricle precludes accurate quantitation of the changes of volume in the ventricle by the simple formulas proposed by previous authors. This phenomenon may serve to explain the considerable variability that is found in the present study and in the literature.

The imposition of a chronic work load (pulmonary artery constriction) on the right ventricle increases ventricular muscle mass. This is associated with increased ventricular stroke work when the animal is standing awake, during infusions of norepinephrine, and under conditions of exercise (running on a horizontal treadmill). Studies two weeks after release of chronic pulmonary artery constriction reveal stroke volume and cardiac output are increased during standing at rest, during norepinephrine infusion, and during exercise. Studies eight weeks after removal of pulmonary artery bands show that stroke volume and cardiac output are approaching the normal range. Right ventricular hypertrophy and right ventricular stroke work decline progressively and apparently in parallel in the weeks following release of chronic pulmonary artery constriction. The stroke work capacity of the ventricle seems related to the presence of right ventricular hypertrophy. With a reduction in outflow tract resistance, the stroke volume for a given set of circumstances is markedly increased. From this standpoint, the work capacity of the right ventricle may be taken as a determinant of stroke volume and cardiac output. Decrease of systemic vascular resistance and relative insensitivity of systemic vasoreceptors to norepinephrine were observed after the release of chronic pulmonary artery constriction. These phenomena have roles in the production of the observed hyperdynamic circulatory state, but their contributions to its genesis are secondary to the major role of the hypertrophied right ventricle.

In these experiments we have demonstrated that: 1. Right ventricular outflow-tract pressure gradients of significance can be induced in normal dogs by a sympathomimetic amine which increases the rate and force of ventricular contraction. 2. Such outflow-tract pressure gradients are magnified by the addition of other inotropic drugs, such as acetyl strophanthidin and calcium chloride. 3. These outflow-tract pressure gradients are not the result of an increase in the volume and rate of blood flow but are due to forceful contraction of the infundibulum.

It has been suggested that the pressor effect of hypertonic solutions of sodium chloride on the Pulmonary circulation results from spasm of the pulmonary veins at their junction with the left atrium. These studies demonstrate that the increased resistance in the pulmonary vessels develops upstream to this site and that it may result primarily from mechanical blockage of vessels by clumped erythrocytes rather than from vasoconstriction.

The ratio of the mean systolic transaortic valvular gradient to the mean systolic left ventricular pressure times 100 yields a percentage that represents the portion of left ventricular pressure-volume work per stroke lost because of outflow-tract obstruction. The percentage of the left ventricular stroke work loss and the area of the aortic orifice have been estimated in 49 patients with aortic valvular stenosis and two open-chest dogs with varying degrees of supravalvular aortic constriction. Left ventricular stroke work loss of 30% or greater was associated with calculated aortic valve areas of 1.0 cm 2 (or 0.60 cm 2 /m 2 ) or less. These values are representative of serious obstruction to left ventricular outflow, that is, approximately 75% or greater reduction of normal orifice size. The calculation of the percentage of left ventricular stroke work loss, besides being simple, is based upon the most reliable measurements obtainable at left heart catheterization, that of the pressure pulses.