Réjane M. Harvey

The Influence of Hydrogen Ion Concentration and Hypoxia on the Pulmonary Circulation

Pulmonary hypertension has been found to be reversible in certain patients with, cor pulmonale due to chronic bronchitis, bronchiolitis, and/or emphysema. In these individuals, as disturbances in gas exchange are corrected, pulmonary artery pressures fall (1). The high degree of correlation between the level of pulmonary artery pressures and the degree of hypoxemia (2, 3) as well as the pressor response to acutely induced hypoxia (4, 5) has implicated a reduced oxygen tension within the lungs as a major factor in the appearance of pulmonary hypertension (6). Since these patients almost invariably demonstrate hypercapnia, carbon dioxide tension has also been invoked as a cause of pulmonary hypertension (3). Anatomic reduction of the pulmonary vascular bed cannot be assigned a dominant role in the genesis of this hypertension because of its reversibility. Nonetheless, we may assume that the effects of reactivity of the vascular compartment to various stimuli will be more readily discernible in the presence of a restricted bed. Liljestrand has recently come to the conclusion that an increased hydrogen ion concentration in the blood is the chemical stimulus for pulmonary

Some Effects of Digoxin upon the Heart and Circulation in Man Digoxin in Chronic Cor Pulmonale

The effects of acute digitalization upon the dynamics of the circulation were observed in patients with chronic cor pulmonale, using the technic of cardiac catheterization. The state of the circulation was further investigated in the same patients following recovery from failure. The mode of action of intravenous digoxin is discussed, and a tentative concept of the pathogenesis of chronic cor pulmonale is presented.

Influence of chronic pulmonary disease on the heart and circulation

Abstract 1.1. Studies of both cardiac and pulmonary function were made in forty-eight cases of chronic pulmonary disease. The pathogenesis of pulmonary hypertension and the evolution of chronic cor pulmonale have been considered. 2.2. Pulmonary arterial hypertension was present at rest in thirty-nine of the forty-eight patients studied. 3.3. In chronic pulmonary emphysema anoxia was shown to be the important abnormality since it was directly or indirectly responsible for the circulatory complications found in these patients. The reversible nature of these circulatory complications in emphysema was demonstrated and its importance with regard to therapy was stressed. It would appear that in patients with chronic cor pulmonale and emphysema cardiac failure is generally characterized by a high cardiac output. 4.4. In patients with silicosis and emphysema the pulmonary hypertension is less likely to be reversible since it stems from anatomic alterations in the pulmonary vascular bed rather than from anoxia. When chronic cor pulmonale and cardiac failure develop in this type of patient, the cardiac output is not elevated. This emphasizes the point that chronic cor pulmonale in failure is not always of the high output type. 5.5. The circulatory changes found in the group of patients with diffusion fibrosis do not appear to be related to anoxia but probably spring from the anatomic lesions produced by the disease processes themselves.

Mechanical and Myocardial Factors in Rheumatic Heart Disease with Mitral Stenosis

Sixteen patients with rheumatic heart disease and pure mitral stenosis, studied by cardiac catheterization, are presented to illustrate the relative importance of mitral block and myocardial insufficiency in this disease. Analysis of hemodynamic data permitted a separation of those patients with predominantly mechanical mitral block from those in whom myocardial insufficiency appeared to be the predominant lesion. The importance of recognizing the existence of the latter group is emphasized, since commissurotomy will not be of benefit in such cases.

Some Effects of Nitroglycerin upon the Splanchnic, Pulmonary, and Systemic Circulations

Splanchnic, pulmonary, and systemic hemodynamics were studied in 18 patients afterthe sublingual administration of nitroglycerin. The drug, contrary to expectations, produced an over-all vasoconstrictive effect on the splanchnic circulation rather than vasodilatation. There was no evidence of venous pooling in this bed, and indeed the data may indicate a splanchnic supportive role in augmenting venous return to the heart with disengorgement of its own volume. In contrast, there was vasodilatation and pooling of blood in the pulmonary vascular bed. The systemic circulation probably sustains several effects by nitroglycerin, including arterial vasodilatation. A direct change in large artery distensibility probably explains the modest fall in systolic blood pressure seen. Further decline in arterial pressure may depend on venous pooling of a small or large degree. Probably the fall in systemic and specific organ flows is also linked to decreased venous return and the vascular readjustments provoked thereby. Pulsus alternans was produced by nitroglycerin, a previously unreported effect of the drug, but the mechanism by which it arose could not be defined.

Hemodynamic Studies in Rheumatic Heart Disease

Hemodynamic studies were made in 42 patients with rheumatic heart disease with various valvular lesions and in different stages of cardiac function. These studies include observations not only at rest, but also during exercise, following the acute administration of Digoxin, and after recovery from failure. The relationship between symptomatology and hemodynamic findings were considered and the importance of differentiating between mechanical block and left ventricular myocardial failure as causes for pulmonary artery hypertension is stressed.

THE RELATIONSHIP BETWEEN ELECTRICAL AND MECHANICAL EVENTS IN THE CARDIAC CYCLE OF MAN

In studying the dynamics of the heart beat, the relationship between electrical and mechanical events in the cardiac cycle has been of fundamental importance. The basic concepts of this relationship have been defined by Lewis (1925) and Wiggers (1923) and their co-workers. Sir Thomas Lewis provided indirect information on these events in the right auricle of man. Animal experiments, supplemented by such indirect information as could be obtained from venous and arterial pulse wave tracings, recording of heart sounds, etc., in man were used .by Wiggers to anticipate the probable normal sequence of events in the cardiac cycle. More precise information may now be obtaiped using the method of right heart catheterization. With direct measurements from within the right heart chambers and pulmonary artery, coupled with peripheral arterial pulse wave and electrocardiographic recordings, the nqrmal course of electrical and mechanical events may be more clearly defined in man and abnormalities in contraction and conduction of the diseased heart may be further elucidated. The data thus obtained will supplement the results obtained by many other investigators and will be analysed and discussed in the light of their studies.

Quantitative radiocardiography. I. Theoretical considerations.

The theoretical background and limits of radiocardiography for the measurement of cardiac output, and of right ventricular and pulmonary blood volumes, are discussed. Injection of a known amount of radioiodinated (I131 ) human serum albumin (RIHSA) into the right atrium, and concomitant recording of a double-peaked time activity curve by means of a shielded scintillation detector placed over the precordium, allows measurement of cardiac output. The geometric arrangements that best approach ideal conditions are described. It is shown that the physiologic significance of the value for output as measured from the radiocardiograms varies with the indicator-flow ratio in 2 sides of the heart. The necessary conditions for measurement of right ventricular volumes from the radiocardiograms are presented, and the theoretical limits of the technic are evaluated. The problem of the measurement of pulmonary blood volume (PBV) from RIHSA radiocardiograms is-discussed. While it is not possible to make a direct measurement of mean PBV from RIHSA radiocardiograms, the limits within which the volume lies are indicated. (P.C.H.)

The Effect of Digoxin in the Splanchnic Circulation in Ventricular Failure

Splanchnic hemodynamics were examined in 22 patients with heart disease, 16 of whom had evidence of ventricular insufficiency at the time of study. The response of the splanchnic vasculature to the exhibition of intravenous digoxin was also studied in nine of these subjects.Ventricular insufficiency was associated with splanchnic vasoconstriction proportional to a generalized increase in peripheral vascularresistance. Splanchnic blood volume was disproportionately increased with respect to total blood volume in patients having visceral congestion with right ventricular failure and combined ventricular failure. A significant relationship between central venous pressure and splanchnic blood volume was demonstrated in these cases. The greater elevation of the former than of the latter suggested the presence of splanchnic venoconstriction.The vascular readjustment to digoxin resulted in a relative intensification of the already existing vasoconstriction of the splanchnic bed as compared to the diffuse systemic vasodilatation which occurred at the same time as the consequence of the inotropic action of the drug: estimated splanchnic blood flow and splanchnic blood volume diminished at a time when systemic flow rose and peripheral vascular resistance decreased. The ultimate distribution of the volume of blood translocated out of the splanchnic bed during this process remains to be determined.

Quantitative Radiocardiography: III. Results and Validation of Theory and Method

The method of quantitative radiocardiography has been applied to the study of cardiac output, right ventricular and pulmonary blood volume in cardiovascular normals, emphysematous subjects, and patients with various types of heart disease. The values of blood flow obtained by means of this technic have been compared with those measured simultaneously by the direct Fick method. A linear correlation has been demonstrated between QRIHSA and QFick, with a regression coefficient of 1.0395 ± 0.0566, when appropriate correction has been made for the contribution of activity in the paracardiac tissues. The principle of the measurement of right ventricular rate of emptying from the fractional decay rate of the precordial counting during the passage of the indicator through the right heart has been validated. The right ventricle behaves essentially as a mixing chamber; a constant fraction of its volume is ejected with each systole. The variability of the emptying rate does not exceed the limits expected on the grounds of statistics of radioactive measurements in normal and in cardiac patients. The significance of the variability observed in emphysematous patients has been discussed. The measured ventricular rates of emptying are reproducible in repeated curves recorded after injection of RIHSA or dissolved Kr85; are little affected by change of the position of the tip of the injecting catheter; or by small changes in the position of the collimator. The right ventricular end-diastolic and residual volumes have been found to average 221 ± 50 ml. and 128 ± 34 ml. respectively, in 18 normal subjects. The calculated pulmonary blood volume in 18 normal subjects averages 313 ± 58 ml./M.2 The significance of this value and the possible extreme range of error resulting from the method have been assessed.