Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidization and multinucleation.

Morphological changes in human myocardium associated with pressure overload-induced left ventricular hypertrophy were studied in 22 normal and 21 hypertrophic hearts obtained at autopsy. Samples were obtained from the left lateral ventricular wall, half way between the apex and the base. Myocyte dimensions, polyploidization, multinucleation and relative volume fractions were studied. Regression analysis in relation to indexed heart weight yielded statistically significant correlation coefficients for myocyte volume: r = 0.69 (P less than 0.001), for degree of polyploidization: r = 0.77 (P less than 0.001), for number of nuclei per myocyte: r = 0.47 (P less than 0.01) and for volume fraction of myocytes: r = 0.32 (P less than 0.05). Approximate numbers of myocytes and connective tissue cells per left ventricle were calculated. Correlation coefficients related to indexed heart weight were r = 0.34 (P less than 0.05) for the number of myocytes and r = 0.76 (P less than 0.001) for the number of connective tissue cells. Based on regression analysis in relation to indexed heart weight, we calculated that a doubling of indexed heart weight was associated with an increase in mean myocyte volume by 65%, degree of polyploidization by 24%, multinucleation by 7%, number of myocytes by 20% and number of connective tissue cells by 141%. The volume percentage of myocytes decreased by 6% in favour of the connective tissue fraction. These changes in myocardial composition indicate that the term 'hypertrophy' inadequately describes the actual myocardial changes in response to pressure overload.     

Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy

To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte nuclei/yr in the left and right ventricular myocardium, respectively. This loss in muscle mass was accompanied by a progressive increase in myocyte cell volume per nucleus in both ventricles. Left ventricular myocytes enlarged by 110 microns3/yr, whereas right ventricular myocytes increased by 118 microns3/yr, resulting in a preservation of ventricular wall thickness. However, the cellular hypertrophic response was unable to maintain normal cardiac mass. Left and right ventricular weights decreased by 0.70 and 0.21 g/yr, respectively. In conclusion, loss of cells and enlargement of the remaining myocytes may represent the structural basis for the reduced compensatory capacity of the aged heart and together may contribute to the development of myocardial dysfunction and failure in the elderly.     

Myocyte cell loss and myocyte hypertrophy in the aging rat heart

To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 3, 10 to 12 and 19 to 21 months of age. Systemic arterial pressure, left ventricular pressure and its first derivative (dP/dt) and heart rate were comparable in the three animal groups. In the interval between 3 and 10 to 12 months, mean myocyte cell volume per nucleus increased 53 and 26% in the left and the right ventricle, respectively. The total number of myocyte nuclei remained constant in either ventricle. In the following period, between 10 to 12 and 19 to 21 months, a 39% further cellular hypertrophy on the left side of the heart was found in association with an 18% loss of cells in the ventricle. Cell loss was accompanied by discrete areas of interstitial and replacement fibrosis in the subendocardium. In contrast, no myocardial damage was observed in the right ventricle, and the measured 35% additional enlargement of myocytes occurred without a change in cell number. Thus, the aging left ventricle is composed of a smaller number of hypertrophied cells. Cellular hypertrophy may explain the unaltered cardiac function of the aged myocardium.     

Left ventricular echocardiographic and histologic changes: Impact of chronic unloading by an implantable ventricular assist device

Objectives. We studied the effects of chronic left ventricular unloading by a ventricular assist device and assessed left ventricular morphologic and histologic changes.Background. The implantable left ventricular assist device has been effective as a “bridge” to cardiac transplantation. Although there are reports documenting its circulatory support, little is known about the effects of chronic left ventricular unloading on the heart itself.Methods. We performed intraoperative transesophageal echocardiography at the insertion and explantation of a HeartMate left ventricular assist device in 19 patients with end-stage heart failure. They were supported by the assist device for 3 to 153 days (mean [±SD] 68±33). Measurements were taken retrospectively to obtain left atrial and ventricular diameters and interventricular septal and posterior wall thicknesses. Histologic examinations were made from the left ventricular myocardial specimens of 15 patients at the times of insertion and explantation for heart transplantation. Insertion and explantation specimens were compared qualitatively (0 to 3 scale) for wavy fibers, contraction band necrosis and fibrosis, with quantitative measurement of minimal myocyte diameter across the nucleus.Results. Left atrial and left ventricular diastolic and systolic diameters decreased immediately after insertion of the left ventricular assist device (from 46 to 35, 63 to 41 and 59 to 36 mm, respectively, all p < 0.001). Left ventricular wall thickness increased from 10 to 14 mm (p < 0.001) for the interventricular septum and from 10 to 13 mm for the posterior wall (p < 0.001). No echocardiographic measurements showed significant subsequent changes at the chronic stage. Myocardial histologic findings demonstrated a reduction in myocyte damage (from 1.9 to 0.5, p < 0.001, for wavy fiber and from 1.3 to 0.2, p < 0.01, for contraction band necrosis) and an increase in fibrosis (from 1.3 to 1.9, p < 0.05), but without significant change in myocyte diameter (from 15.6 to 16.8 μm, p = 0.065).Conclusions.Left ventricular unloading with the implantable assist device induces an immediate increase in wall thickness, consistent with the reduction in chamber size, thereby decreasing wall stress. Chronic unloading allows myocardial healing and fibrosis without evidence for ongoing myocyte damage or atrophy. Left ventricular assist device insertion may have a role in “resting” the ventricle for selected patients with heart failure.     

Relationship of left ventricular mass to defibrillation threshold for the implantable defibrillator: a combined clinical and animal study

Defibrillation results when a critical mass of myocardium is depolarized. The relationship between echocardiographic determinations of left ventricular mass, volume, and cavity radius to wall thickness ratio and defibrillation threshold for the implantable defibrillator was examined. Ten patients with two large patch defibrillating lead systems were studied. Defibrillation threshold was determined intraoperatively as the lowest energy terminating ventricular fibrillation. Left ventricular mass, volume, and radius/posterior wall thickness ratio were calculated from two-dimensional echocardiograms. A significant correlation was found between left ventricular mass and defibrillation threshold (r = 0.78, p less than 0.01). The correlations between defibrillation threshold and left ventricular volume (r = 0.59) and radius/wall thickness ratio (r = 0.55) were not significant. Subsequently, 11 dogs undergoing defibrillation trials with a transvenous catheter and a chest wall patch were studied. Defibrillation threshold was defined as the lowest energy-terminating ventricular fibrillation (four separate attempts). Subsequently, the heart was dissected, and the left ventricle (including the septum) was weighed. The correlation between left ventricular weight and defibrillation threshold (r = 0.76) was significant (p less than 0.01). We conclude that noninvasive assessment of left ventricular mass and direct measurement of left ventricular weight are significantly correlated with defibrillation threshold and consistent with the critical mass hypothesis.     

Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans

Objectives. The present investigation was designed to evaluate the growth reserve capacity of the aged and senescent myocardium.Background. Aging affects the ability of the heart to sustain alterations in ventricular loading, and this phenomenon may be coupled with attenuation of the hypertrophic reaction of the myocardium. However, because myocyte cellular hyperplasia has been documented experimentally in the old heart, a similar adaptation may also occur in humans and play a role in this process.Methods. The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 13 hypertrophic hearts obtained at autopsy from patients 80 ± 4 (mean ± SD) years old. An identical number of nonhypertrophic hearts collected from subjects 76 ± 7 years old were used as control hearts.Results. A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% augmentation in the total number of myocyte nuclei in the ventricular myocardium. However, a 55% increase in right ventricular weight was the result of a 59% increase in the aggregate number of myocyte nuclei, with no change in myocyte cell volume. These cellular processes were associated with a 95% and 83% enlargement of the myocardial interstitium in the left and right ventricle, respectively.Conclusions. Myocyte nuclear and possibly cellular hyperplasia appear to be the prevailing growth mechanism of the overloaded aging myocardium. Proliferation of myocyte nuclei and connective tissue accumulation are the major determinants of ventricular remodeling in the hypertrophic senescent heart.     

Cellular basis of chronic ventricular remodeling after myocardial infarction in rats.

To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased ninefold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Chamber dilation was the consequence of the combination of gross anatomic and cellular changes consisting, in the presence of small infarcts, of a 6% and a 19% increase in transverse midchamber diameter and in average myocyte length per nucleus, respectively. In the presence of large infarcts, transverse and longitudinal chamber diameters expanded by 27% and 11%, respectively, myocyte length per nucleus expanded by 26%, and the mural number of myocytes decreased by 10%. In conclusion, decompensated eccentric ventricular hypertrophy develops chronically after infarction, and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistance of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

Growth and development of ventricular walls in complete transposition of the great arteries with intact septum (simple transposition)

A morphometric assessment of the ventricles was made in a series of 31 normal hearts and in 69 hearts with complete transposition of the great arteries and intact septum (simple transposition). Specimens representing different age groups were compared in order to investigate the development of the ventricular walls during infancy and early childhood.In the series of normal hearts the left ventricular wall was always thicker than the right ventricular wall when related to both age and body weight. The increase in thickness of the left ventricular wall showed some linear correlation with both increasing age and weight; that of the right ventricular wall did not. In the hearts with simple transposition, the mean thickness of the left ventricular wall was similar to that of the normal wall at birth, but thereafter the rate of increase was less than normal. There was no linear relation between increasing wall thickness and either age or weight. The thickness of the right ventricular wall (already significantly greater than normal at birth) showed a weak linear relation with increasing age but not with body weight. Right ventricular muscle volume index was higher than that of the normal heart but right ventricular cavity volume index was not increased. Left ventricular cavity volume index increased with age, but muscle volume showed no difference from the normal.At birth the left ventricle in simple transposition is in some respects morphologically better adapted than the right ventricle to support the systemic circulation. However, increase in cavity size and failure of the wall thickness to develop may prevent the left ventricle from supporting the systemic circulation after the 1st months of life. The right ventricle in transposition, although structurally unsuited to support the systemic circulation, is able to adapt by increasing wall thickness, at least in early life.     

Myocardial mechanical, biochemical, and structural alterations induced by chronic ethanol ingestion in rats.

To determine the effects of moderate ethanol consumption on the mechanical, biochemical, and structural characteristics of the heart, myocardial mechanical performance, contractile protein enzyme activity, and the number and size of myocytes were measured in male Fischer 344 rats after the ingestion of 30% oral ethanol. Papillary muscles removed from the left ventricle were greater in length, weight, and cross-sectional area than the corresponding muscles from the right side. However, no differences were found between control and ethanol-treated myocardium when either the left or right side was compared separately. Chronic ethanol ingestion resulted in an increase in resting tension in left ventricular muscles, with no alteration in peak developed tension. Moreover, time to peak tension was significantly prolonged, whereas a depression was observed in the peak rate of isometric tension development. Isotonically, left muscles from ethanol-treated rats revealed a prolongation of time to peak shortening and a marked depression in the velocity of shortening at physiological loads. No changes were noted in muscles from the right ventricle. Contractile protein enzyme activity revealed no differences in myofibrillar Mg(2+)-ATPase activity in right and left ventricular myocardium between control and ethanol-treated rats in the presence of EGTA. However, at physiological activating levels of calcium, an upward shift of the myofibrillar Mg(2+)-ATPase activity-calcium curve occurred in left myocardium, whereas a depression in this relation was seen in the right ventricle. As a result of chronic ethanol intake, a decrease was noted in the volume percent of myocardium occupied by myocytes, and that myocyte cell volume per nucleus was found to remain essentially constant throughout the various layers of the ventricular wall. Importantly, a 14% significant decrease in the total number of myocyte nuclei was demonstrated in the left ventricular myocardium of rats on chronic ethanol consumption. Thus, chronic but moderate alcohol ingestion resulted in depressed contractile performance, alterations in myofibrillar Mg(2+)-ATPase activity, and myocyte loss. These events may serve to function as preliminary indicators of the onset of heart failure of alcoholic origin in this animal model.     

Size dependence of the end-systolic stress/volume ratio in humans: implications for the evaluation of myocardial contractile performance in pressure and volume overload

The end-systolic stress/volume ratio is currently recognized as a relatively load-independent index of myocardial contractile performance, but its dependence on ventricular size may limit its value for interpatient comparisons. In this study, the relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was angiographically analyzed in 104 patients with normal coronary angiograms. Eighteen patients had a normal ventricle, 24 had aortic stenosis, 18 had aortic regurgitation, 9 had mitral regurgitation and 35 had cardiomyopathy. An inverse relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was demonstrated in the normal group (r = 0.72, p less than 0.001); subjects with a larger left ventricle had a reduced index but, presumably, the same degree of contractility as that of subjects with a smaller ventricle. Attempts to normalize values by using end-diastolic volume or body surface area were unsuccessful. A similar inverse relation was demonstrated in the aortic stenosis group (r = 0.48, p less than 0.05), probably because hypertrophy helps to keep wall stress normal or low despite progressive ventricular enlargement in these patients. The end-systolic stress/volume ratio was also inversely related to left ventricular chamber size in patients with volume overload due to aortic regurgitation (r = 0.80, p less than 0.001) and in those with cardiomyopathy (r = 0.84, p less than 0.001). However, at a given left ventricular end-diastolic volume, the end-systolic stress/volume ratio was higher in patients with aortic regurgitation than in those with cardiomyopathy, suggesting better contractile performance for a comparable degree of ventricular dilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging.

Magnetic resonance imaging (MRI) of a modified short-axis section of the heart, in 36 patients with chronic pulmonary diseases, consisting of 19 patients with pulmonary hypertension (PH group; mean pulmonary arterial pressure > or = 20 mm Hg) and 17 patients without pulmonary hypertension (non-PH group) was evaluated to study the configuration of the right ventricle. Parameters of right ventricular hypertrophy, including right ventricular wall thickness (RVWT) and the ratio of RVWT to left ventricular posterior wall thickness (RVWT/LVPWT), with this method were significantly larger in the PH group than in the non-PH group (p < 0.01). RVWT and RVWT/LVPWT correlated well with mean pulmonary arterial pressure (r = 0.90, p < 0.001 and r = 0.89, p < 0.001), total pulmonary resistance (TPR; r = 0.88, p < 0.001 and r = 0.85, p < 0.001), and pulmonary arteriolar resistance (PAR; r = 0.83, p < 0.001 and r = 0.81, p < 0.001). This method of setting a patient in a supine position and slicing with single-oblique sections may seem overly simple compared with Dinsmore's double-oblique short-axis section of the heart, but it is more convenient in practice. These results suggest that a modified short-axis section of the heart by MRI provides valid clinical configurational information concerning the right ventricle on which to base a noninvasive diagnosis of cor pulmonale.     

Myocardial systolic function of the left ventricle along the long axis in patients with essential hypertension: a study by pulsed tissue Doppler imaging

OBJECTIVES: Myocardial contractility of the left ventricle along the long axis in hypertensives is not well characterized. The systolic velocities of the left ventricular myocardium along the long axis were measured by pulsed tissue Doppler imaging in patients with mild to moderate essential hypertension. The relationships between the systolic velocity of left ventricular myocardium along the long axis and the blood pressure, and the left ventricular geometry were investigated. METHODS: The study included 60 untreated hypertensive patients (hypertension group) and 59 age-matched healthy subjects (control group). M-mode echocardiograms were recorded, and the relative wall thickness, left ventricular mass index and left ventricular end-systolic stress were calculated. The peak systolic velocities of the left ventricular posterior wall motion (Sw) were measured by pulsed tissue Doppler imaging. RESULTS: The Sw was significantly lower in the hypertension group than in the control group (8.3 +/- 1.9 vs 9.2 +/- 2.0 cm/sec, p < 0.05). The Sw was correlated inversely with systolic blood pressure (r = -0.31, p < 0.005), diastolic blood pressure (r = -0.25, p < 0.0001), interventricular septal thickness (r = -0.41, p < 0.0001), left ventricular posterior wall thickness (r = -0.39, p < 0.0001), relative wall thickness (r = -0.33, p < 0.001), and left ventricular mass index (r = -0.37, p < 0.001) in all subjects. CONCLUSIONS: The systolic velocity of the left ventricular myocardium along the long axis is decreased in patients with mild to moderate essential hypertension, and is negatively correlated with blood pressure and the severity of left ventricular concentric hypertrophy.     

Changes in modalities of left ventricular filling associated with aging in normal subjects: secondary to increase in blood pressure and left ventricular mass?

The mechanisms by which aging alters the pattern of left ventricular diastolic filling are still uncertain. To gain more insight into this tissue, the independent contributions of age, sex, heart rate, arterial blood pressure and left ventricular mass (as well as various indexes of left ventricular morphology and function) to left ventricular diastolic filling abnormalities, were investigated by echocardiography in 81 normal subjects (18 to 84 years of age, mean 50), carefully screened to avoid the confounding effects of coronary artery disease and systemic hypertension. With advancing adult age, we found a significant increase in: body mass index (r = 0.25; p less than 0.02), systolic (r = 0.58; p less than 0.0001), pulse (r = 0.61; p less than 0.0001) and mean (r = 0.40; p less than 0.0001) arterial blood pressure; left ventricular wall thickness (r = 0.30; p less than 0.006); left ventricular mass (r = 0.32; p less than 0.004); left ventricular end-diastolic volume (r = 0.24; p less than 0.03); and peak systolic wall stress (r = 0.22; p less than 0.04). Pulsed Doppler analysis of mitral inflow showed a significant age-related decline in the peak early filling velocity (r = -0.51; p less than 0.001), and in the ratio of early and late diastolic filling velocity (r = -0.65; p less than 0.0001). Conversely, duration of isovolumic relaxation (r = 0.77; p less than 0.0001), peak late diastolic flow velocity (r = 0.39; p less than 0.001), and diastolic pressure half time (r = 0.34; p less than 0.01) increased significantly with age. "Stepwise" multivariate linear regression analyses showed that the ratio of early to late diastolic peak filling velocity was independently related only with age (R2 = 0.56; p less than 0.0001) while the isovolumic relaxation time was independently related with age (R2 = 0.48; p less than 0.0001) and duration of cardiac cycle (R2 = 0.06; p less than 0.008). Age-related changes in body mass index, blood pressure, peak meridional wall stress and left ventricular mass index did not show any independent relationship to Doppler parameters of left ventricular filling or duration of isovolumic relaxation. The results of the present study suggest that the effect of age on left ventricular filling modalities and duration of isovolumic relaxation are independent of age-related changes in blood pressure, left ventricular mass, morphology and systolic function.     

Blood pressure and echocardiographic measures in children: the Bogalusa Heart Study

M mode echocardiograms were obtained from 654 healthy subjects, 7 to 22 years of age, whose diastolic blood pressure levels remained in the same height-, race-, and sex-specific decile during two biannual examinations. Echocardiographic measures of heart size, obtained according to the recommendations of the American Society for Echocardiography, were compared across the entire systolic and diastolic blood pressure distributions. Echocardiographic indexes of left heart size varied as a function of both blood pressure levels and body size. Significant positive correlations were present between systolic blood pressure and different measures of left ventricular size. Left ventricular wall thickness in systole correlated with systolic blood pressure (r = .42, p less than .0001), and persistence of this relationship was noted after adjustment for body size. Left ventricular wall thickness in diastole correlated with blood pressure before adjustment (r = .31, p less than .0001), but the relationship was not significant after adjustment for body size. The ratio of left ventricular thickness to chamber size (systole) correlated with systolic blood pressure levels both before and after adjustment for body size (r = .20 and r = .22, p less than .001). Male subjects of both races demonstrated significantly higher adjusted left ventricular mass, left ventricular wall thickness, and left ventricular chamber size. Adjusted left ventricular wall stress was significantly related to both systolic (r = .14) and diastolic blood pressure levels (r = .14, p less than .001). Measures of left ventricular wall thickness increased throughout the entire blood pressure distribution, indicating a consistent trend rather than a threshold effect seen only in the highest blood pressure groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of regional contractile dynamics and pathological findings of the left ventricular wall in patients with hypertrophic cardiomyopathy

To investigate the relationship between regional contractile dynamics and regional myocardial lesions of the left ventricular wall in patients with hypertrophic cardiomyopathy (HCM), autopsy findings of 11 patients were compared with their ante mortem echocardiographic findings. The regional systolic wall thickenings (%RWT) of the interventricular septum (IVS) and left ventricular posterior wall (LVPW) obtained using M-mode echocardiography were converted into % normalized RWT (%NRWT) by the averaged %RWT in 15 normal subjects. The %NRWT was compared with the wall thickness obtained by echocardiography and/or autopsy, and histological findings, such as the myocardial fibrosis ratio, disarray area ratio, and mean myocyte diameter. 1. There were no significant correlations among wall thickness of the left ventricle, the myocardial fibrosis ratio, the disarray area ratio, and the mean myocyte diameter of each segment. 2. The %NRWT in 22 segments of the 11 patients with HCM was not significantly related to the echocardiographic wall thickness at end-systole, the autopsy wall thickness, the mean myocyte diameter and the disarray area ratio, but that correlated significantly with the echocardiographically-determined wall thickness at end-diastole (r = -0.53, p less than 0.02), and with the myocardial fibrosis ratios (r = -0.59, p less than 0.005). 3. The %NRWT in the IVS was significantly less than that in the LVPW. The %NRWT in all segments of the LVPW was significantly related to the myocardial fibrosis ratios (r = -0.80, p less than 0.005), but was not related to the wall thicknesses or the disarray area ratios.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reliability of echocardiographic and electrocardiographic parameters in assessing serial changes in left ventricular mass

A reliable noninvasive index of left ventricular mass would be useful in following patients with valvular heart disease and left ventricular hypertrophy. We reviewed concurrent electrocardiograms and echocardiograms from 54 subjects, 39 patients with aortic or mitral valve disease and 15 normal subjects. Pre- and early postoperative echocardiographic estimates of left ventricular mass in 17 patients who had valve replacements correlated well (r = 0.96, p < 0.001) and demonstrated little change in mean values despite altered left ventricular dimensions. Echocardiographic estimates of left ventricular mass were, therefore, used as a standard for evaluating other noninvasive indices. Precordial electrocardiographic voltage showed a weak correlation with left ventricular mass in the study group as a whole (r = 0.59, p < 0.001), but no correlation in patients with volume overload (r = 0.36, p = NS). In 18 patients who had preoperative and three separate postoperative studies at least eight weeks apart, changes in left ventricular cross-sectional area (an index of left ventricular mass which corrects for changes in left ventricular volume) closely followed alterations in left ventricular mass. However, changes in posterior wall and interventricular septal thickness often resulted from altered ventricular volume and did not accurately reflect directional changes in left ventricular mass. Serial changes in electrocardiographic voltage were similarly unreliable. We conclude that left ventricular mass and cross-sectional area by echocardiography allow accurate noninvasive assessment of left ventricular mass, whereas wall thickness and electrocardiographic changes do not.     

Comparison of M-mode echocardiography and angiography in the evaluation of left ventricular hypertrophy

The authors analysed in a group of 82 patients with a symmetric left ventricle and a homogeneous ventricular wall thickness the reliability of M-mode echocardiography in recognizing left ventricular hypertrophy. In concentric hypertrophies, a sufficient diagnostic criterion is ventricular wall thickness. Measurement of the interventricular septum offers a better correlation with angiographic values (r = 0.609, p less than 0.001) than measurement of the posterior wall (r = 0.358, p less than 0.01); a correct diagnosis can be determined in 84%. In excentric hypertrophies, the hypertrophy must be assessed on the basis of calculating the left ventricular mass. The most accurate of echocardiographic methods proved to be the calculation according to the authors' own formula (r = 0.760, p less than 0.001), which recognizes left ventricular hypertrophy correctly in 85%. The diagnostic correctness of Teichholz' formula is 80% and of the cubic formula 74%. Fortuin's equations proved to be of no value for documenting ventricular hypertrophy. In a group of 13 patients with hypertrophic cardiomyopathy, the correlation between angiographic and echocardiographic values of the left ventricular mass was very low (r = 0.534, p = 0.05).     

Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects

Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass.     

Cellular basis of ventricular remodeling after myocardial infarction.

To determine whether acute left ventricular failure associated with myocardial infarction leads to architectural changes in the spared nonischemic portion of the ventricular wall, large infarcts were produced in rats, and the animals were sacrificed 2 days after surgery. Left ventricular end-diastolic pressure was increased, whereas left ventricular dP/dt and systolic pressure were decreased, indicating the presence of severe ventricular dysfunction. Absolute infarct size, determined by measuring the fraction of myocyte nuclei lost from the left ventricular free wall, averaged 63%. Transverse midchamber diameter increased by 20%, and wall thickness diminished by 33%. The number of mural myocytes in this spared region of the left ventricular free wall decreased by 36% and the capillary profiles by 40%. Thus, side-to-side slippage of myocytes in the myocardium occurs acutely in association with ventricular dilation after a large myocardial infarction. In order to analyze the chronic consequences of myocardial infarction on ventricular remodeling, a second group of experiments was performed in which the left coronary artery was ligated and the functional and structural properties of the heart were examined 1 month later. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), a 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased 9-fold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Thus, decompensated eccentric ventricular hypertrophy develops chronically after infarction and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistence of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

Comparison of myocardial changes between pressure induced hypertrophy and normal growth in the rat heart

To evaluate differences in tissue composition between hearts with pressure overload hypertrophy and normal hearts of comparable weight, 30 rat hearts with aortic constriction of 4, 10 and 30 days, and nine hearts of sham operated controls were studied. Surgery was performed at age 70 days. Morphometric analysis of myocardial tissue sections revealed (1) myocyte hypertrophy in left ventricular myocardium of hypertrophic hearts was proportional to heart weight, and in normal growth myocyte volume increased in proportion to heart weight; (2) myocyte number in left ventricular myocardium was identical in hypertrophic and normal hearts; (3) non-muscle cell proliferation was proportional to heart weight identically in hypertrophic and normal hearts; (4) volume fractions of myocytes were significantly lower in hypertrophic hearts [0.76(SD 0.05)] than in normal hearts [0.82(0.04)]; (5) volume fractions of all nuclei, myocyte nuclei and non-myocyte nuclei were similar in hypertrophic and normal hearts; (6) measured ventricular DNA content increased with heart weight identically in hypertrophic and normal hearts, and equalled DNA content calculated using the data on tissue composition. Neither right ventricular weight nor right ventricular DNA content were affected by the presence of left ventricular hypertrophy. We conclude that left ventricular hypertrophy due to aortic constriction in the rat resulted in changes of myocardial tissue composition similar to the changes associated with normal growth. Tissue composition of hypertrophic rat hearts corresponds strikingly to that of normal rat hearts with comparable heart weight, although myocardial changes in hypertrophy develop considerably faster than in normal growth.