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The hypertrophied right ventricle of the dog with pulmonary stenosis exhibited a greater than normal uptake of digoxin 5 min after intravenous administration. After 1 hr the digoxin concentration had fallen and was not different from the normal, this latter result suggesting that hypertrophy per se did not change the ventricle's binding affinity for digoxin per unit mass. Greater initial binding of digoxin by the hypertrophied ventricle was probably associated with some function of the mechanical activity of the stressed ventricle and/or with greater tissue delivery of digoxin in greater myocardial blood flow.

Eighty-two adults with various chronic heart diseases were studied by cardiac catheterization and quantitative biplane left ventriculography with filming at 12 per second. Mean left ventricular ejection rate (dVe/dt), which is the change in chamber volume with respect to time, was calculated from the films. The patient series included those with left ventricular volume overload, pressure overload, myocardial disease, idiopathic hypertrophic subaortic stenosis, and one patient with a ventricular septal defect. dVe/dt correlated significantly with stroke volume and both parameters varied over nearly a ten-fold range of values. dVe/dt correlated poorly with the ejection fraction, whereas dVe/dt divided by end-diastolic volume correlated significantly with the ejection fraction. dVe/dt alone bas minimal value in assessing left ventricular function but when dVe/dt is normalized for end-diastolic volume, it may reflect the contractile function of the left ventricle. Therefore, ventricular ejection rate is similar to other assessments of ventricular pump function (ie, stroke volume, strokework, and power) and only has significance in evaluating left ventricular myocardial function when preload is considered.

The relative effects of chronic pressure overload and chronic volume overload on left ventricular diastolic chamber stiffness were examined using a combined hemodynamic and ultrasonic technique in 27 patients. The slope of the left ventricular pressure-diameter relation in late diastole was measured and found to be steep in the groups with pressure or volume overload (9.0 ± 1.8 mm Hg/mm for pressure overload, 5.6 ± 0.9 mm Hg/mm for volume overload) compared with a control group (2.2 ± 0.2 mm Hg/mm). When this slope was normalized for either pressure or diameter, chamber stiffness remained high in the pressure-overloaded ventricles but was only slightly increased in the volume-overloaded ventricles compared with control. Ventricular wall thickness was much greater in pressure-overloaded ventricles (15.6 ± 1.0 mm) than it was in normal (9.0 ± 0.4 mm) ventricles but only slightly increased in volume-overloaded ventricles (10.6 ± 0.9 mm). The large increases in both effective and normalized diastolic stiffness indexes associated with chronic pressure overload suggest an increase in intrinsic left ventricular chamber stiffness, possibly related to an increase in wall thickness. In contrast, chronic volume overload results in only slight increases in normalized diastolic stiffness indexes and wall thickness. It is suggested that differences in the pattern of hypertrophy, which result in a significant disparity in ventricular wall thickness between the two conditions, best account for the observed differences in diastolic left ventricular chamber stiffness.

This investigation was designed to quantify left ventricular and left atrial volume, volume change, systolic output, and ventricular mass in 31 patients with isolated left ventricular pressure overload secondary to aortic stenosis (AS, n = 14) or coarctation of the aorta (n = 17). These parameters were compared with normal standards and with data from a group of nine patients with a combined pressure and volume overload due to aortic stenosis plus aortic or mitral insufficiency (AS + AI or MI). Volumes were calculated from biplane cineangiocardiograms exposed at 60 frames/sec. Left ventricular end-diastolic volume (LVEDV) was significantly lower than normal in patients with AS (57 ± 11 cc/m 2 ), but was normal (73 ± 12 cc/m 2 ) in patients with coarctation. An increase in the ejection fraction (LVEF) was found in both groups averaging 0.73 ± 0.12 in AS patients and 0.69 ± 0.09 in coarctation patients. Patients with AS + aortic or mitral insufficiency (AI or MI) showed elevated LVEDV (103 ± 29 cc/m 2 ), but had a normal ejection fraction. The LV mass was significantly increased in all groups: normal, 82 ± 10 g/m 2 ; AS, 126 ± 41 g/m 2 ; coarctation, 130 ± 44 g/m 2 ; and AS + AI or MI, 168 ± 42 g/m 2 . The left ventricular systolic index and left atrial maximal volume were both normal in patients with pure pressure overload but were significantly increased in patients with combined pressure and volume overload. The low LVEDV in patients with AS as well as the normal volume in patients with coarctation occurred in the presence of elevated LV end-diastolic pressure and indicates a decrease in LV diastolic distensibility in patients responding to an isolated LV pressure overload by significant muscular hypertrophy without dilatation.

Summary The development and application of quantitative angiocardiography has contributed to the understanding and clinical management of patients with valvular heart disease. The method of quantitative angiocardiography is reviewed with particular emphsis on filming techniques, calculations of ventricular volume and principles of x-ray magnification. The information available from the ventricular volume curve is described in quantitative mechanical terms. The usefulness of left ventricular chamber dimensions for study of chamber geometry, wall forces, and ventricular function are also delineated. The pathophysiologic mechanisms operative in chronic valvular heart disease are analyzed in response to a volume or pressure overload. The adaptive mechanisms of dilation and hypertrophy are examined in terms of diastolic wall stress or dilatation and hypertrophy are examined in terms of diastolic wall stress or preload and peak systolic wall stress or afterload. Angiocardiography can be clinically applied to quantitate regurgitation in valvular heart disease, to define indices of ventricular function, to facilitate selection of patients for surgical repair, to evaluate cardiac performance after surgery, and to describe prognosis of patients with valvular disease.

Studies in 540 children with congenital heart disease have shown correlations between the orthogonal electrocardiogram and the hemodynamic load placed on the right and left ventricles. Using the Frank lead system, the maximum spatial voltage directed to the left has been shown to reflect the degree of pressure or volume overload of the left ventricle in patients with aortic stenosis and septal defects and even in the cyanotic lesions tetralogy of Fallot and complete transposition of the great arteries. The maximum spatial voltage directed to the right has been found to correlate well with pressure overload of the right ventricle in patients with pulmonic stenosis and septal defects. The direction of rotation of the vectorcardiographic loop in the horizontal plane has been shown to reflect well the relative hemodynamic loads on the two ventricles, and thus presumably the relative degrees of left and right ventricular hypertrophy present. In certain lesions, the electrocardiographic-hemodynamic correlations are close enough to allow the Frank electrocardiogram to be of significant help in the clinical management of children with congenital heart disease.

Ouabain had no effect on myofibrillar adenosine triphosphatase (ATPase) activity in normal, hypertrophic, and failing hearts with concentrations of calcium chloride varying from 0 to 5.0 mM. The quantitative effects of CaCl 2 on myofibrillar ATPase were the same in all groups studied. At necropsy it was found that myofibrillar ATPase activity of heart tissue from patients with clinical and pathologic diagnoses of failure from left ventricular volume and pressure overload was significantly lower than that of normal controls. The ATPase activity in patients with failure due to right ventricular volume and pressure overload was not significantly lower than that in normal controls. There was no difference in myofibrillar ATPase activity between normal left and normal right and between failing left and failing right ventricles. The difference demonstrated at necropsy between normal and failing hearts was not a function of age or of hypertrophy per se. Myofibrillar ATPase activity of hypertrophic nonfailing surgical pulmonary infundibular tissue was the same as that of normal postmortem ventricles. The ATPase activity of failing surgical papillary muscle in a small number of experiments was in the range of that found in failing postmortem ventricles.

In two preceding papers increased pressure load (afterload) was found to accelerate whole heart protein synthesis and amino acid transport in the perfused working rat heart (Hjalmarson and Isaksson 1972, Ahren et at. 1972). To further analyse this effect, sucrose gradient analysis of the postmitochondrial supernatant was performed to evaluate reactions involved in the ribosome cycle. When hearts were perfused in vitro under control conditions with buffer containing normal plasma levels of amino acids and with glucose as substrate, levels of polysomes decreased and levels of ribosomal subunits increased. These findings together with a decreased rate of protein synthesis indicated that a block in initiation of peptide chains had developed during perfusion. Perfusion of hearts with increased afterload increased the levels of polysomes and decreased the levels of ribosomal subunits and accelerated protein synthesis. The effects were obtained both when glucose and palmitate were used as substrate. Insulin further increased the levels of polysomes in pressure overloaded hearts and the ribosome profiles attained by overload in presence of insulin were identical to those obtained from unperfused hearts. Increased levels of polysomes and decreased levels of ribosomal subunits together with an increase in protein synthesis suggested that pressure overload stimulated reactions involved in the initiation of polypeptide chains. It is concluded that increased pressure load increases levels of initiation factors or changes the activity of enzymes regulating initiation processes in the ribosome cycle.

Left ventricular contractile state was evaluated in 20 children ages 3 to 11 years with normal left hearts and in 15 children ages 2 to 16 years with a left ventricular pressure overload. All patients were studied during diagnostic cardiac catheterization with catheter-tip micromanometry. Pressure-velocity curves were obtained during isovolumic systole by plotting (dp/dt)/28 P versus developed or total pressure (P). Computer analysis of five cardiac cycles was used to yield one composite pressure-velocity curve for each patient with both linear and second-degree polynomial curve analysis. The developed pressure method yielded higher values for the calculated V max index, (dp/dt)/28 P at zero P than the total-pressure method for all patients. Normal standards were defined for both methods. The V max index calculated with total pressure as well as peak (dp/dt)/28 P was significantly less than normal for the hypertrophy group. The V max index calculated with developed pressure was not significantly different from normal for the entire hypertrophy group, but four of the 15 patients showed a depression of contractile state defined as a value for the V max index less than 2 sd of normal. These results indicate the potential importance of preoperative and postoperative estimation of contractile state in patients with a left ventricular pressure overload in evaluation of possible irreversible alterations of contractility that may accompany myocardial hypertrophy.

The maximal, no-load, velocity for the contractile element (V max ) was estimated in 45 patients. The patients included: 17 with normal left ventricular dynamics; eight with volume overload, compensated; 11 with volume overload, decompensated; three with pressure overload; and six with cardiomyopathy. Contractile element velocity (V CE ) during isovolumic contraction was estimated in two ways: (1) from left ventricular pressure data alone, where V CE =(1/28.8p) (dp/dt), and (2) pressure data combined with measurement of left ventricular geometry (right anterior oblique cine). V max obtained in these two ways agreed well for most patients (r = 0.82). In the normal patients, V max varied from 1.46 to 2.64 muscle lengths per sec; in contrast that of the patients with cardiomyopathy varied between 0.71 and 1.34 muscle lengths per sec. Other indices of contractility (ejection fraction, peak dp/dt, peak velocity of circumferential fiber [peak V CF ], peak V CE , and V CE at zero stress) were compared on the basis of statistical correlation and consistency of other clinical evidence (presence or absence of congestive failure). Good correlation was obtained between V max and peak V SE (r = 0.68). Ejection fraction and peak V CF were less sensitive. Neither the peak rate of pressure rise or V CE at peak stress show any significant correlation with V max or clinical state. Previous studies have shown that V max can be evaluated from pressure data alone; this study confirms this finding in patients with mitral regurgitation as well as in those with normal outflow impedance.

In patients with chronic heart disease discrepancies have been demonstrated between left ventricular end-diastolic pressure and end-diastolic volume. In the present study we compared the end-diastolic pressure with chamber size, mass, contractility, wall forces and pressure volume work, and examined the determinants of left ventricular stroke volume and stroke work. We studied forty-seven patients (six with normal hemodynamics, seven with mitral stenosis, eighteen with compensated volume overload, three with decompensated volume overload, six with pressure overload, three with idiopathic myocardial hypertrophy and four with primary myocardial disease). No relationship was found between end-diastolic pressure and end-diastolic volume, mass, wall forces, ejection fraction and stroke work. End-diastolic stress in the patients with volume overload frequently was within 2 S.D. (standard deviations) of the normal. Only in the groups with pressure overload did end-diastolic pressure correlate with peak systolic stress. In the normal subjects and those with compensated volume overload end-diastolic volume correlated significantly with left ventricular stroke volume and stroke work. Increased end-diastolic volumes were consistently accompanied by increased left ventricular masses in all groups with chronic heart disease. Deviations from the normal resting stroke volume can result from changes in preload, contractility and afterload, and these variables can be expressed as end-diastolic wall stress, ejection fraction and peak systolic wall stress. In chronic heart disease ventricular distensibility varies from patient to patient as well as in the course of the disease and such diastolic pressure-volume relationships differ from those encountered during acute hemodynamic alterations. Under chronic conditions ventricular dilatation rarely occurs without hypertrophy, and in pressure overload ventricular hypertrophy without chamber enlargement may be encountered. In either chronic pressure or chronic volume overload without myocardial failure, left ventricular mass is more consistently related to stroke work than either end-diastolic pressure or volume alone. Therefore, in chronic heart disease in the resting state, end-diastolic pressure, volume, mass, contractility, wall stress and distensibility must be considered in the function of the left ventricle, and any principle which utilizes a single variable may not consistently predict ventricular stroke volume or stroke work.

Mechanical overload in the heart induces two different types of adaptational mechanisms. (a) From a qualitative point of view, the maximum speed of shortening is depressed in relation to a myosin isoenzymic change responsible for decreased ATPase and, although the relaxation appears normal from a physiological point of view, the existence of an abnormality in Ca2+ uptake in the sarcoplasmic reticulum has been well documented. Both of these processes appear to improve efficiency by decreasing the heat produced per gram of tension. The existence of a large broadening of the action potential has now been well established, but it remains unexplained at the biochemical level. The functioning of mitochondria is rather controversial, and although it has been shown that they are both more abundant and smaller, the reason why their respiratory index changes remains unknown. (b) From a quantitative point of view, the adult heart adapts to overload by increasing its mass. This is mainly a consequence of a hypertrophy of the myocytes and a mitotic multiplication of nonmuscular cells. Data suggest that myocyte amitotic divisions may occur, at least in humans, and perhaps in very sizeable experimental hypertrophy. To this phenomenon has been added the development of polyploidy of myocyte nuclei, which seems to be specific to certain species. The stimulation of protein synthesis occurs very soon after pressure overload, and is delayed in volume overload; protein lysis also increases, although this is controversial. The process occurs whatever the proteins. This is accompanied by increased nuclear activity and a stimulation in RNA synthesis, which is especially precocious for messenger RNA. Among the very early events which could be potential signals for protein synthesis, attention has been focused on polyamine, RNA polymerase, and uridine kinase. The trigger mechanism, of course remains hypothetical. As a trigger for protein synthesis, several data suggest an increase in wall stress and stretch; a drop in efficiency is suggested as a trigger for qualitative changes.

Depressed myocardial contractility with paradoxically increased oxygen consumption has been demonstrated in previous studies of pressure overload hypertrophy. To determine whether altered mitochondrial respiration participates in the abnormal energetics of this muscle, right ventricular hypertrophy (RVH) was produced in 12 cats by pulmonary artery banding. A polarographic muscle bath was used to study eight control and eight RVH papillary muscles, and the respiration of mitochondria isolated from these right ventricles was characterized. RVH muscles demonstrated depressed force-velocity and length-tension curves. The myocardial oxygen consumption per gram of peak active tension was increased from 0.65 ± 0.05 nliters/mg beat -1 (control) to 1.10±0.07 nliters/mg beat -1 (RVH) ( P -1 (control) to 19.9±0.8 natoms/mg min -1 (RVH) ( P < 0.001). The altered oxygen cost of active isometric tension in the RVH muscles was linearly correlated with the altered rate of mitochondrial state 4 oxygen consumption ( r = 0.91). Ruthenium red, a compound that blocks mitochondrial calcium uptake, reduced the rate of RVH state 4 oxygen consumption to the control level. The present study suggests a mechanism for the abnormal myocardial oxygen consumption in pressure overload hypertrophy and relates it to nonphosphorylating mitochondrial respiration linked to calcium transport.

Several recent studies have shown that myocardium hypertrophied by a pressure overload exhibits depressed indexes of contractility; there is further deterioration with the superimposition of congestive heart failure. For isotonic contractions of cat right ventricular papillary muscles hypertrophied by pulmonary arterial banding, there are decrements in both the velocity and extent of shortening against any given afterload. For isometric contractions, the maximal active tension generated is reduced, the time required to reach peak tension is prolonged, and the rate of tension development is lessened. Because these contractile indexes have been defined as determinants of the oxygen consumption (MVO2) of isolated myocardium, the MVO2 of isotonic and isometric contractions of this same preparation of hypertrophied and failing myocardium was examined. Both in hypertrophied myocardium and in hypertrophied and failing myocardium, the expected parallel decrements of contractile indexes and MVO2 did not occur. The MVO2 of isotonic contractions was normal, and that of isometric contractions was increased. This paradoxical dissociation of depressed contractility and augmented MVO2 is apparently related to the pressure stress, since we have found normal contractile indexes and MVO2 with the same extent of hypertrophy induced by a volume overload. More recent studies suggest that the mechanism for the increased MVO2 of pressure-induced hypertrophy of the myocardium might lie in increased nonphosphorylating respiration by its mitochondria.

Right ventricular (RV) volumes were calculated from biplane cineangiocardiograms in 46 patients undergoing diagnostic cardiac catheterization. Validation of methodology was performed by comparison of known and calculated volumes of postmortem RV casts as well as by comparison of cineangiocardiographic RV and left ventricular (LV) stroke volumes of patients without shunts or valvular insufficiency. Seven infants, 2 , P < 0.001) as well as decreased RV systolic indices (SI) (3.71 ± 0.68 vs 4.66 ± 1.10 liters/min/m 2 , P < 0.05). There were no differences between normal infants and older children for RV ejection fraction (EF), RVEDV/LVEDV = 1.01, RVSI/LVSI = 0.99, and RVEF/LVEF = 1.04 vs 0.99. In 13 patients with isolated pulmonary stenosis, RVEDV, RVEF, RVSI, RVEDV/LVEDV, and RVSI/LVSI were not different from normal, but RVEF/LVEF averaged 1.13 vs 0.99 in normal infants, P < 0.05. In contrast, 11 patients studied with atrial septal defect or total anomalous pulmonary venous connection had significant increases in RVEDV (128 ml/m 2 ), RVSI (9.34 liters/min/m 2 ), RVEDV/LVEDV (2.36), RVSI/LVSI (2.81), and RVEF/LVEF (1.17), but normal values for RVEF. There was a significant linear relationship between Q p /Q s from oxygen data and RVSI/LVSI. In three patients studied an average of 1 year following atrial septal defect (ASD) repair, RVEDV remained elevated. In volume overload, alterations in RV volume characteristics are apparent and can be useful in shunt estimation; adaptation to an RV pressure overload, however, is not associated with detectable volume alterations.

In certain forms of heart disease when the diagnosis is readily apparent from clinical examination, it would be desirable to assess the degree of hemodynamic abnormality by the simplest method. If electrocardiographic data could provide a sufficiently accurate indication of altered function, the need for cardiac catheterization might be obviated. However, detailed electrocardiographic criteria1, 2 do not appear to correlate with the weight of the ventricle or the thickness of the ventricular wall.3 A more definitive result might be obtained from correlations of the electrocardiographic details with function, as attempted by Cosby and co-workers,4 rather than with anatomic structure. For this functional approach, Cabrera and Monroy5 disseminated the concepts of the systolic and the diastolic overloading of the ventricle. Statistical support for these ideas is not yet available even though modified views have been presented.6 Studies of correlation between the severity of pulmonary stenosis and electrocardiographic evidence of right ventricular hypertrophy7–11 disclose a wide variability. From a functional view, the simplicity of the abnormality makes pulmonary stenosis an ideal disease to study; there is solely a systolic or pressure overload of the right ventricle. In order to overcome obstruction to outflow through the pulmonary valve, the right ventricular systolic contraction takes a longer time and becomes more powerful. Recent investigators12, 13 have compared the peak right ventricular systolic pressure with various aspects of the electrocardiogram. But as Haywood, Selvester, and Griggs14 realized, pressure data alone are insufficient to assess hemodynamic function; flow must also be considered. For example, to double the flow rate through an orifice, the pressure gradient must be quadrupled if there is no change in resistance to flow due to altered turbulence. The purpose of this study is to determine the relationships between the electrocardiographic data and hydraulic data that consider the effect of blood flow.

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.

The purpose of this study was to evaluate left ventricular (LV) structure-function interplay in aortic stenosis. LV structure was assessed from endomyocardial biopsies obtained in 27 patients with aortic stenosis. Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching) and endocardial fibrosis were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from 6 pre-transplantation donor hearts whereas other 11 patients with normal cardiac function served as hemodynamic controls. LV biplane cineangiography and high-fidelity LV pressure measurement were carried out in all patients. Systolic function was assessed by LV biplane ejection fraction, diastolic function by time constant of relaxation, peak filling rates and passive elastic properties. Total collagen volume fraction (7.3 versus 1.6%, p < 0.01) as well as the degree of cross-hatching (1.7 versus 0.8 grade, p < 0.01) were significantly increased in patients with aortic stenosis with respect to controls. Endocardial fibrosis was present in 11/27 patients with aortic stenosis and in no patients of control group. In aortic stenosis in presence of increased total collagen volume fraction there were no changes in systolic and diastolic function, whereas in presence of changes in collagen architecture ejection fraction was depressed and passive elastic properties increased. In conclusion, in aortic stenosis, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered. A prolongation of relaxation was present in aortic stenosis and appears to be mediated by muscle hypertrophy per se.

Summary Recent clinical studies of pulmonary embolism indicate that typical ECG changes of acute right ventricular overload become evident only with severe pulmonary hypertension. The present study was performed to determine whether less obvious yet consistent ECG changes are present during mild and moderate pulmonary hypertension and to what extent hypoxia modifies the ECG response. Three series of experiments were performed; each employed 6 dogs. The orthogonal ECG (McFee system) was recorded at 3 levels of pulmonary artery (PA) mean pressures: control, 20 and 40 mm Hg in closed-chest dogs with and without hypoxia. Mean arterial pO 2 was 53 mm Hg in the hypoxic series. Pulmonary hypertension was induced by means of a PA balloon catheter. Right ventricular (RV) volumes were determined from biplane cineangiograms in a separate series. The ECG analysis was performed utilizing digital computer techniques. No significant ECG changes were produced by a mean PA pressure of 20 mm Hg despite a 17% increase in RV end-diastolic volume above control values. At 40 mm Hg and a 45% increase in RV volume, dogs in the series without hypoxia showed a small but significant posterior shift of the initial QRS vector. Hypoxic dogs demonstrated directionally similar but more prominent changes with significant posterior displacement of both early and late QRS vectors and posterior-superior ST displacement. Thus, this study confirmed clinical data suggesting that the ECG is an insensitive indicator of acute RV pressure overload. ECG changes present at high PA pressures were accentuated by hypoxia.

Surgical treatment of multiple valve disease requiring replacement of two valves is associated with a high mortality. Different combinations of mitral and aortic valve stenosis or incompetence result in different changes of adaptation by the heart. The left ventricular response to pure pressure overload, as in combined mitral and aortic stenosis, is concentric hypertrophy, whereas the changes that occur in response to pure volume overload, as in combined mitral and aortic regurgitation, are dilatation and hypertrophy. The records of 124 patients with a variety of combinations of mitral and aortic valve disease were reviewed. Surgical mortality could be directly related to the presence of left ventricular concentric hypertrophy and the small size of the left ventricular chamber. Surgical treatment was accomplished with a surgical mortality of 52.5 percent (21 of 40 patients) when both valves were stenotic; however, when botb valves were insufficient the surgical mortality was only 9 percent (3 of 32 patients). This presentation includes correlation of surgical results with the clinical, electrocardiographic roentgenographic and hemodynamic data. An attempt is made to clarify the indications for double valve replacement. The operative technique used in the treatment of these patients with combined mitral and aortic valve disease is described.

Study of left ventricular pressure-volume relations in man has been limited by technical problems associated with left ventricular angiography. A new approach to this problem using simultaneous recording of left ventricular pressure and left ventricular volume (determined by echocardiography) was applied in 21 patients. Pressure-volume plots, constructed from pressure and volume values sampled at 20 or 40 msec intervals, had characteristic shapes for the states studied: normal, pressure overload, volume overload, and myocardial disease. These curves closely resembled pressure-volume plots previously determined by others from quantitative angiography. The area inscribed by these plots was integrated to calculate left ventricular stroke work. Left ventricular stroke work index (gram-meters/m 2 ) was in the range previously reported for the various states; normal-41 ± 12, pressure overload-102 ± 14, volume overload-136 ± 36, myocardial disease-65 ± 19. Inspection of the pressure-volume plots allowed assessment of valvular regurgitation by the characteristic deformation of the loop during "isovolumic" contraction and relaxation. Study of diastolic filling allowed qualitative assessment of left ventricular compliance. Patients with pressure overload had stiffer ventricles, with high diastolic pressure at lower volume, than normal or volume overload patients. In summary, a new method is described for the beat-to-beat analysis of left ventricular pressure-volume relations in man.

T he Polarcardiograph gives the direction and magnitude of the heart vector as continuous tracings known as polarcardiograms (PCGs).’ In the diagnosis of infarction the superiority of the PCC over the single electrocardiogram (EC

In vitro pressure overload was found to accelerate protein synthesis in the isolated working rat heart (Hjalmarson and Isaksson 1972 a). Since membrane transport of amino acids is considered to be one rate-limiting step in protein synthesis, the amino acid transport in the isolated rat heart was investigated using the non-utilizable amino acids α-aminoisobutyric acid (AIB) and 1-aminocyclopentane carboxylic acid (cycloleucine). Increased pressure load (afterload) accelerated amino acid uptake after a perfusion period of 15 ruin, and a 50—100% increase in the intracellular to extracellular distribution ratio of the amino acids was seen after 60 min of perfusion. This accelerated uptake was not inhibited by cycloheximide, suggesting that the work load effect was not dependent upon a continuous synthesis of proteins. The accumulation rate continued to be stimulated for some time after normalization of the work load and coronary flow, indicating that the work load effect was not directly linked to coronary flow. Increased preload did not stimulate amino acid uptake. Hearts from hypophysectomized rats showed a decreased concentrative uptake but the amino acid uptake was still accelerated by pressure overload. It is suggested that an increased uptake of amino acids could be of physiological significance in relation to the increased protein synthesis under these conditions.

Systemic and coronary hemodynamics were evaluated in nine young asymptomatic patients with congenital heart disease and nine normal subjects with the same age range to determine the effects of chronic hemodynamic overloading on left ventricular performance, coronary blood flow (CBF), and myocardial oxygen consumption (MVO 2 ). Both at rest and during exercise, the mean values for CBF and MVO 2 were significantly greater in the patients with congenital heart disease than in the normal subjects. The patients did not differ significantly from normal in mean forward flow, total systemic and coronary resistances, mean systolic ejection rate, or excess lactate production. Total stroke work and pressure-time per beat were elevated at rest but differed insignificantly from normal during exercise. Elevated MVO 2 was associated, both at rest and during exercise, with an increased mean arterial pressure in coarctation of the aorta, with increased heart rate and total ventricular output in left-to-right shunts, and with increased pressure-time per minute in both. CBF was closely correlated with MVO 2 and significantly, but less well, correlated with coronary perfusion pressure. MVO 2 exhibited a significant correlation with pressure-time per minute but with no other hemodynamic variable. We conclude that myocardial oxygen consumption is augmented in the hemodynamic overloading of compensated mild congenital heart lesions as reported in this study. It may be that normal values for oxygen usage and coronary flow previously reported in overloaded left ventricles represent reductions, associated with ventricular decompensation, from super-normal values obtained during the compensated phase. The present study also suggests that the stimulus which results in increased metabolic demand is best described, even in shunt lesions, as a pressure overload.

The relation of single cell electrical activity to generation of force was determined for myocardium during the development of hypertrophy induced by pressure loading. Transmembrane potentials and isometric active force at optimal length (P o ) were monitored in isolated right ventricular papillary muscles and trabeculae carneae after inducing chronic right ventricular outflow tract obstruction. Cats subjected to partial pulmonary artery occlusion or to sham operation were studied 1, 3, 7, 10, 21, and > 90 days after surgery. Right ventricular muscles were stimulated at 30/min at optimal length in Tyrode's solution (36°C). Muscles from sham-operated and 1 day pressure-loaded hearts had electrical and mechanical properties similar to normal muscles. Right ventricular peak systolic and end-diastolic pressures were increased for 1 and 3 day pressure-loaded hearts; the percent of right ventricular water was increased for 3, 7, and 10 day pressure-loaded hearts. Muscles from 3 day pressure-loaded ventricles had significantly decreased P o , maximum rate of force development, time to peak force, and duration of contraction compared with normal muscles, and their action potential plateaus originated at more negative potentials (mean 24.7 mv for 11 muscles). The alteration in action potential configuration was less obvious in muscles studied 7 and 10 days after partial pulmonary artery occlusion and did not occur 21 and > 90 days after pressure loading; however, P o and maximum rate of force development remained decreased, although time to peak force and duration of contraction returned to normal for preparations from 7, 10, 21, and > 90 day pressure-loaded ventricles.

Left heart volumes were determined angiographically in 50 subjects of whom 18 had no abnormality of the left heart, 12 had lesions causing pressure overload of the left ventricle, and 20 had lesions causing volume overload of the left ventricle. The left heart volumes were in the normal range in the presence of pressure overload, but, with volume overload, end-diastolic, end-systolic, and atrial volumes were in excess of normal. A linear relationship was demonstrated between end-diastolic and end-systolic volumes, regardless of the pressure load on the ventricle. Thus, for all but one of the cases studied, total left ventricular ejection volume formed a nearly constant proportion of end-diastolic volume.

Recent animal investigations have indicated that myocardial hypertrophy may be accompanied by a depression of muscle function as analyzed in terms of length-tension and force-velocity relationships. Myocardial function was evaluated in these terms in 14 children with left ventricular hypertrophy (LVH) secondary to aortic stenosis or coarctation of the aorta and 10 children with normal left hearts who were undergoing diagnostic cardiac catherization. Serial left ventricular volumes were calculated from biplane cineanangiocardiograms exposed at 60/frames sec, and left ventricular pressure was recorded simultaneously using a catheter tip transducer. Left ventricular circurrferential stress (LVS), LV circumference at the equator (LVC), and LV contractile element velocity (VCE) were calculated. Mean values for VCE at isostress points during isovolumic contraction were not different from normal in 9 patients with moderate LVH (LV Mass 115±13 vs. normal 82±10 g/M2). In 5 patients with more severe LVH and LV Mass averaging 156±31 g/M2, VCE was significantly depressed from normal during isovolumic systole indicating a depressed force-velocity relationship. In addition 4 of the 5 patients with severe LVH had depressions of LV stress at isocircumference points at end-systole when compared with normal children suggesting a depressed length-tension relationship. These date indicate that severe left ventricular hypertrophy in children may be accompanied by impaired muscle function when expressed in terms of basic muscle mechanics.

Regression of hypertrophy was studied in 96 adult rats following aortic debanding (dB). Controls were 146 continuously banded (B), and 116 sham-operated (S) rats. Sacrifice was at 3, 7, 14, 21 and 28 days for LV mass, RNA, DNA and hydroxyproline (OHP). Hemodynamics were obtained at 28 days. Aortic gradients were 60-130 mmHg in B, and none in dB and S. Initial (dP/dt)p−1, in Sec−1, was lower in dB (212) than in B (235) and S (234) although not significantly. Early debanding (after 10 days of aortic constriction) showed drop in LV mass from 35% to 11% above C (P