Endothelin converting enzyme inhibitor protects development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension

We evaluated the effects of FR901533, endothelin converting enzyme inhibitor, on development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), continuous subcutaneous injection of FR901533 (100 mg/kg/day) was started. Right ventricular systolic pressure, mass ratio of right ventricle to left ventricle, right ventricular wall thickness, right ventricular myocardial fiber diameter, percent medial thickness, and percent smooth muscle area in pulmonary arteries were significantly less in rats that received FR901533 than in the control with monocrotaline on day 28. Both immunoreactivities of endothelin-1 in pulmonary arteries and plasma endothelin-1 levels were observed significantly less in rats treated with FR901533 than in the control with monocrotaline. There were significant increased immunoreactivities of endothelin-B receptor in pulmonary arteries in rats that received FR901533 as compared with those in the control with monocrotaline. FR901533 (100 mg/kg/day), protected the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.     

MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD), the development of pulmonary hypertension is common. This study was performed to assess the signs of right ventricular (RV) pressure overload and RV failure in COPD. In 8 COPD patients without primary cardiac disease, RV wall thickness, mass, and end-diastolic volume were measured by cardiac-triggered cine MRI. MR phase-contrast velocity quantification was used to measure stroke volume and the patterns of flow into and out of the RV. Data of patients were tested versus those of a control group matched for age (n = 8). Results showed that the RV wall thickness was increased (.6 +/- 0.1 vs 0.4 +/- 0.1 cm, P < .001). RV mass was increased (67 +/- 11 vs 57 +/- 5 g, P < .005). RV stroke volume was decreased (57 +/- 13 vs 71 +/- 13 ml, P < .01), but RV ejection fraction was not different. In the main pulmonary artery flow, the quotient of acceleration time divided by ejection time was decreased (33 +/- 5% vs 38 +/- 4%, P < .05), which is indicative of pulmonary hypertension. In conclusion, this MRI protocol provides a tool to assess the effects of RV pressure overload in COPD before heart failure has become manifest.     

Angiographic and morphologic features of the left ventricle in Ebstein's malformation

Quantitative and qualitative cineangiographic analysis of the left ventricle (LV) was performed in 26 patients with isolated Ebstein's malformation, having a mean age of 23 +/- 17 years. Nine autopsied hearts with isolated Ebstein's malformation were submitted to morphologic and morphometric analysis. In 4 of the cases, it was possible to make a direct correlation between the angiographic data obtained during life and the autopsy findings. On the basis of the LV end-diastolic volume we identified 3 groups of patients: 7 with volume <60 ml/m2, another 7 with volume between 60 and 80 ml/m2, and 12 with volume >80 ml/m2. The LV ejection fraction was reduced in 2 patients with normal LV end-diastolic volume and in 6 with increased LV end-diastolic volume. The ratio of ventricular mass to LV end-diastolic volume was always adequate, but a reduction of the ventricular contractive performance (end-systolic pressure to end-systolic volume ratio <3 mm Hg/ml/m2) was found only in patients with a dilated left ventricle. No correlation was demonstrated between the extent of the atrialized component of the right ventricle (mean value 67 +/- 31 cm2, range 13 to 133) and the LV dimensions. All but 2 patients showed a leftward diastolic displacement of the ventricular septum, but in only 1 did this produce an elongated shape of the left ventricle. Sixteen had anomalies of LV dynamics: 10 with hypokinesia (3 of the posterior wall, 4 of the apex, 1 of the inferior wall, 1 of the septum, and 1 global), 6 with dyskinesia (1 of the posterior wall, 2 of the apex, 1 of the posterior wall and apex, 1 of the superior part of the septum, and 1 of the anterior wall), and 8 with premature diastolic distension of the anterobasal wall. Morphometric analysis produced mean values for myocytes of 59 +/- 10%, for the interstitium of 21 +/- 4%, and for fibrous tissue of 20 +/- 9% (normal 4 +/- 1%). Five autopsied hearts had a prolapsing and/or dysplastic mitral valve.     

Perindopril in monotherapy of primary hypertension--6 month observation

We evaluated effects of perindopril (Prestarium-SERVIER) in the treatment of the primary hypertension in 41 patients (mean age 41.6) in the I or II degrees WHO using 24 ambulatory blood pressure measurement and echocardiography. Investigation were performed before and after 3 and 6 months of the treatment. Initially 4 mg of perindopril was given and individually was increased after 3 months to 8 mg according to 24 ambulatory blood pressure measurement results. We obtained significant decrease of blood pressure in 3 (134.6/86.6 mm Hg) and in 6 (135/88, 9 mm Hg) months of treatment in comparison to baseline values (141.8/91.1 mm Hg), decrease of left ventricular mass to 244.4 g in 3 and 248.8 g after 6 months (baseline 258.5 g), as well as index of left ventricular mass, wall thickness and left ventricular end diastolic volume. There was no significant differences in: ejection, heart rate, left ventricular inflow on the successive investigations. Good effect of perindopril we observed in 31 patients (75.6%) after 6 months of treatment. We did not observe any serious side effects of perindopril. CONCLUSION: Perindopril in treatment hypertension effectively reduces the level of blood pressure (systolic, diastolic and mean) without any effect on heart rate. Prestarium reduces left ventricular mass, intraseptal wall thickness and left ventricular end diastolic volume. There is no influence on inflow to the left ventricle as well as on ejection fraction.     

Ventricular interdependence: significant left ventricular contributions to right ventricular systolic function

This article reviews diastolic and systolic ventricular interaction, and clinical pathophysiological conditions involving ventricular interaction. Diastolic ventricular interdependence is present on a moment-to-moment, beat-to-beat basis, and the interactions are large enough to be of physiological and pathophysiological importance. Although always present, ventricular interdependence is most apparent with sudden postural and respiratory changes in ventricular volume. Left ventricular function significantly affects right ventricular systolic function. Experimental studies have shown that about 20% to 40% of the right ventricular systolic pressure and volume outflow result from left ventricular contraction. This dependency of the right ventricle on the left ventricle helps to explain the right ventricular response to volume overload, pressure overload, and myocardial ischemia. The septum and its position are not the sole mechanism for ventricular interdependence. Ventricular interdependence causes overall ventricular deformation, and is probably best explained by the balance of forces at the interventricular sulcus, the material properties, and cardiac dimensions.     

Left ventricular geometric patterns and QT dispersion in untreated essential hypertension

The spectrum of left ventricular adaptation to hypertension, different types of hypertrophy patterns, and QT dispersion in different types of hypertrophy was investigated in 107 patients with untreated essential hypertension and 30 age- and gender-matched normal adults studied by 12-derivation electrocardiogram (ECG), two-dimensional, and M-mode echocardiography. Left ventricular mass (LVM), body mass index, total peripheral resistance (TPR), relative wall thickness (RWT), and QT dispersion were found to be statistically significantly higher in the hypertension group (P < .001 for all). Among hypertensive patients, 41.1% had both normal LVM and RWT, here called normal left ventricle in hypertension; 10.3% had concentric hypertrophy with increased LVM and RWT; 14.95% had eccentric hypertrophy with increased LVM and normal RWT; and 32.7% had concentric remodeling with normal LVM and increased RWT. Echocardiographically derived cardiac index was higher in the concentric hypertrophy and eccentric hypertrophy patterns (P = .002 and P < .0001, respectively), whereas TPR was higher in the concentric hypertrophy and concentric remodeling patterns (P = .017 and .02, respectively). QT dispersion values were found to be increased in the hypertensive group (P = .001), whereas similar values were calculated for different types of hypertrophy patterns. We conclude that the more common types of ventricular adaptation to essential hypertension are eccentric hypertrophy and concentric remodeling. Concentric hypertrophy is found to be associated with both volume and pressure overload, whereas eccentric hypertrophy is associated with volume overload only and concentric remodeling is associated with pressure overload. But different left ventricular geometric patterns seem to have similar effects on QT dispersion.     

Age-related variation in left ventricular myocardial contractile state expressed by the stress velocity relation

The assessment of ventricular function plays an important role in the pre- and postoperative management of many congenital heart abnormalities. Normal ranges in left ventricular systolic function indices have been defined during childhood and age-related alterations in left ventricular myocardial contractile state have recently been reported. This study was carried out to investigate the developmental changes in left ventricular contractile state expressed by the endsystolic meridional stress (ESS)/rate-corrected velocity of circumferential fiber shortening (VCFc) relation, calculated by echo in normal children and young adults. We examined 146 healthy subjects (80 males and 66 females), mean age 70.85 +/- 63.89 months (range 0.5-228) and body surface area (BSA) 0.807 +/- 0. 47 (range 0.18-2.01) with no clinical and echocardiographic evidence of cardiac disease and with normal blood pressure. The subjects were divided into three groups according to age: <6 months (group 1, n = 32), 6-36 months (group 2, n = 34), and >36 months (group 3, n = 80). Enddiastolic volume and mass (M) of the left ventricle were measured by M-mode Echo. ESS was considered as an index of afterload and the VCFc as an index of systolic ventricular function. The left ventricular ejection time used for the calculation of VCFc was measured from aortic flow obtained by PW-Doppler. The ESS/VCFc relation was used to assess left ventricular contractility. Systolic blood pressure, volume, and mass of the left ventricle increase with age. The gradual increase in pressure despite a stable mass/volume ratio [M/V = 0.900 + (0.0007 x age); r = 0.27, p < 0.005] resulted in a substantial increase of afterload [ESS = 29.78 + (0.116 x age); r = 0.58, p < 0.0001]. VCFc showed an inverse hyperbolic regression with afterload [VCFc = 1.01 + (7.598/ESS); r = 0.59, p < 0.0001]. The regression lines (best linear fit) between VCFc and ESS are significantly different in the three groups. The Y intercept was higher and the slope steeper in group 1 [VCFc = 1.74 - (0.017 x ESS); r = 0.65, p < 0.0005] vs group 2 [VCFc = 1.54 - (0.008 x ESS); r = 0.58, p < 0.001] and group 3 [VCFc = 1.52 - (0.007 x ESS); r = 0.57, p < 0.0001]. These data indicate that, in children, the volume and mass of the left ventricle increase, whereas the M/V ratio remains relatively constant; the progressive increase in arterial blood pressure explains the increase of afterload. The VCFc is higher in the first few years of life compared to that seen in older children due to reduced afterload and increased contractile state. Left ventricular contractility, expressed as ESS/VCFc relation, is thus inversely proportional to age. In the first months of life the left ventricular myocardium exhibits a higher basal contractile state and a greater sensitivity to changes in afterload. For obtaining an accurate assessment of left ventricular function, the ESS/VCFc relation in different age groups should be measured.     

Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy

AIMS: It is not known whether the apparent normality of echocardiographic examination results, in subjects bearing a mutation for hypertrophic cardiomyopathy but without ultrasonic left ventricular hypertrophy, is due to incomplete phenotypic expression, or inaccurate echocardiographic criteria. The aim of this study was to search for echocardiographic abnormalities in these patients. METHODS AND RESULTS: Echocardiography was performed in 100 subjects from two families with a mutation in the beta-MHC (720) or My-BPC (714) genes. We compared genetically affected subjects with an apparently normal left ventricle (thickness < 13 mm) (20 patients), and nonaffected first-degree relatives (61 normal subjects). (1) Patients had a thicker left ventricular wall (9.7 +/- 1.4 vs 8.9 +/- 1.4 mm, P = 0.03), a greater indexed mass (107 +/- 18 vs 97 +/- 17 g. m-2, P = 0.03), a larger left atrium (27 +/- 9 vs 23 +/- 10 mm3, P = 0.09) and lower wall stress (78 +/- 11 vs 89 +/- 15 10(3) dynes. cm-2, P = 0.002); these differences were highly significant after adjustment for height, age and systolic blood pressure either for wall thickness (P = 0.000003), mass (P = 0.005) or atrial volume (P = 0.001), and the ventricular systolic dimension appeared smaller (P = 0.01); (2) results remained significant (P < 0.01) when a lower cut-off value (< or = 11 mm) or only adults (> or = 18 years) were considered; (3) a subanalysis of Family 714 (13 patients, 25 normals matched for sex, age and height) showed the same trends. CONCLUSION: In familial hypertrophic cardiomyopathy, genetically affected subjects with an apparently normal heart by echocardiography show slight ultrasonic structural and functional left ventricular modifications, suggesting that the phenotype of the disease is a continuous spectrum from normal structure to typical hypertrophy.     

Echocardiography in the evaluation of ventricular function

The ultrasonic beam used for quantitative assessment of left ventricular (LV) function traverses the heart in a projection similar to the familiar angiographic left anterior oblique projection. It crosses the anterior wall of the right ventricle, the right ventricular cavity, the interventricular septum, the LV cavity and the posterior wall of the left ventricle. Whereas the cyclic changes of the right ventricular diameter are rarely clearly determined by echocardiography, the easily assessed cyclic changes of the LV endocardial transverse diameter are useful measure of LV FUNCTION. Of practical importance are the percentage of systolic shortening of the LV diameter (%Sh) and the mean velocity of circumferential fiber shortening (VCF). There are several factors, such as placing of the ultrasonic transducer, the shape and size of the LV cavity and rotational movements of the heart as a whole, that influence echocardiographic determination of the transverse LV diameter. In patients with asynergic contraction, %Sh and VCF cannot be used as measures of overall LV performance, but localized contraction disturbances of the septum and the posterior wall may be detected from the reduced extent of wall motion in a given LV segment during a full sweep from the base to the apex. The most important indications for echocardiographic assessment of LV function are valvar diseases with chronic LV pressure or volume overload, and congestive cardiomyopathy. Echocardiography has proved useful in serial evaluation of LV function in patients undergoing valvar heart surgery. Assessment of LV volume by standard echocardiography using the cubic formula is not satisfactory. More accurate determination of volumes is provided by formulas that include the actual ratio of the LV long axis to the minor axis.     

Right ventricular function in congenital heart disease: pressure and volume overload lesions

The right ventricle is often subject to both pressure and volume overload in congenital heart disease. Evaluating right ventricular function in both the native lesion and after surgery in light of these loading conditions, presents a unique challenge for investigators studying these misshapen hearts. The purpose of this article is to briefly delineate what is generally known about right ventricular function in congenital heart disease and to touch on some noninvasive imaging modalities which have helped shed some light on this matter.     

Conversion of complex neonatal Ebstein's anomaly into functional tricuspid or pulmonary atresia

BACKGROUND: Ebstein's anomaly, due to failure of delamination of one or more leaflets of the tricuspid valve (TV), is associated with varying degrees of tricuspid regurgitation (TR) and dysplasia of the right ventricle (RV). Although refinement of tricuspid valvuloplasty and plication techniques have opened the way to a satisfactory outlook for the majority of older children and adults, Ebstein's anomaly presenting at neonatal age, secondary to ineffective forward flow into the pulmonary and systemic circulation, has a reported mortality rate of as high as 75%. In order to improve the dismal outcome in neonatal Ebstein's anomaly, we have strived for early univentricular palliation. PATIENTS AND METHODS: Univentricular repair was performed in five neonates (median age 5 days; range 2-14 days) with Ebstein's anomaly, ductal dependent pulmonary blood flow, severe TR, absence of forward flow across the pulmonary valve, and small left ventricular (LV) area due to right-to-left bowing of the ventricular septum and ineffective LV loading (median indexed LV area 10.5 cm2/m2). In addition, two neonates had moderate pulmonary regurgitation (PR), one with additional pulmonary stenosis. In all patients, the indexed area of the combined right atrium and atrialized RV was greater than that of the combined functional RV, left atrium, and left ventricle (median 22.0 and 20.8 cm2/m2, respectively). The median preoperative systemic oxygen tension was 35 mmHg and the median pH 7.28. Repair consisted of TV closure with a pericardial patch (with the coronary sinus draining into the RV) (n = 3) or, in the presence of PR, resection of the dysplastic TV and division and oversewing of the main pulmonary artery (n = 2), as well as excision of the atrial septum, resection of redundant right atrial wall, and construction of an aortopulmonary shunt (n = 5). RESULTS: The median indexed LV area increased from 10.5 to 18.8 cm2/m2 as a result of more effective loading of the left ventricle. There was no intraoperative or late mortality. The patients were extubated at a median of 7 days postoperatively. At discharge, the median systemic oxygen tension was 46 mmHg. In all five patients, at 6, 7, 10, 12 and 16 weeks of age, a bidirectional cavopulmonary anastomosis has been constructed. CONCLUSIONS: In neonates with Ebstein's anomaly and ductal dependent pulmonary blood flow, rational palliation consists of the surgical creation of tricuspid atresia or, in the additional presence of PR or pulmonary stenosis, the creation of pulmonary atresia. These procedures may result in effective LV decompression and more effective volume loading of the left ventricle with increase of systemic output and improved clinical outcome.     

The cellular basis of dilated cardiomyopathy in humans

The present investigation was designed to evaluate whether end-stage cardiac failure in patients affected by dilated cardiomyopathy (DC) was dependent upon extensive myocyte cell death with reduction in muscle mass or was the consequence of collagen accumulation in the myocardium independently from myocyte cell loss. In addition, the mechanisms of ventricular dilation were analysed in order to determine whether the changes in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chamber dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis. However, the relative contribution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning the potential etiology of collagen deposition in the myocardium and the changes in number and size of ventricular myocytes with this disease. Morphometric methodologies were applied to the analysis of 10 DC hearts obtained from patients undergoing cardiac transplantation. An identical number of control hearts was collected from individuals who died from causes other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-fold increase in left ventricular weight and chamber volume resulting in a 48% reduction in mass-to-volume ratio. In the right ventricle, tissue weight and chamber size were both nearly doubled. Left ventricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myocytes within the wall. Myocardial scarring represented by segmental, replacement and interstitial fibrosis occupied approximately 20% of each ventricle, and was indicative of extensive myocyte cell loss. However, myocyte number was not reduced and average cell volume increased 2-fold in both ventricles. In conclusion, reactive growth processes in myocytes and architectural rearrangement of the muscle compartment of the myocardium appear to be the major determinants of ventricular remodeling and the occurrence of cardiac failure in DC.     

Clinical significance of magnetic resonance and echocardiographic correlations in the evaluation of hypertrophic cardiomyopathy

Relatively few clinical studies have investigated the role of MRI in the patients with hypertrophic cardiomyopathy. To assess MR capabilities in defining the presence, distribution and severity of left ventricular hypertrophy, the prevalence and clinical correlations of right ventricular hypertrophy and the prevalence and clinical implications of structural myocardial abnormalities, MRI and echocardiography were performed on 37 unselected patients with hypertrophic cardiomyopathy. The two methods were in agreement in 100% of cases in diagnosing the disease and classifying left ventricular hypertrophy as asymmetric, concentric or apical, and in 92% of cases in assessing the topographic distribution of hypertrophy of ventricular segments. A statistically significant linear correlation was found between echocardiographic and MR measurements of interventricular septum (r = 0.69, p < 0.0001, SEE = 4) and left posterior wall of the left ventricle (r = 0.67, p < 0.0001, SEE = 2.4). Right ventricular hypertrophy (right anterior wall diastolic thickness > 5 mm) was demonstrated by MRI in 23 of 33 patients (70%). In this group, left posterior wall thickness and left atrial diameter were higher (15 +/- 4 vs 11 +/- 2, p < 0.01 and 45 +/- 9 vs 38 +/- 5 mm, p < 0.05, respectively). On T2-weighted sequences, areas of reduced signal intensity, probably due to myocardial fibrosis, were detected in 16 cases (43%). This group was characterized by higher max. septal thickness (25 +/- 7 vs 21 +/- 6 mm, p < 0.05) and max. left posterior wall thickness (15 +/- 9 vs 7 +/- 8 mm, p < 0.05). All the three cases with dilated and hypokinetic left ventricle showed this kind of tissue abnormality. In conclusion, MRI provided clear, accurate and exhaustive data on the presence and distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. Right ventricular hypertrophy and structural abnormalities of ventricular myocardium can also be detected and quantified. Right ventricular involvement is associated with more severe hypertrophy of left ventricular posterior wall. Structural myocardial abnormalities, probably due to fibrosis, are related to the extent of left ventricular hypertrophy.     

Alterations of the Frank orthogonal scalar leads induced by anaphylactic shock in the rabbit

The anaphylactic shock of the rabbit is characterized by an acute right ventricular overload, accompanied by severe alterations of cardiac electrogenesis. During shock, the mean QRS vector, as measured from the algebraic sum of the Q, R, and S deflections on the three leads, shifts to the right, inferiorly and anteriorly. An injury current quickly appears. The TQ vector points away from the right ventricle. A progressive depolarization on the right ventricular wall is displayed by suction electrodes and the suppression of right ventricular hypertension by a cross circulation produces an almost immediate disappearance of the injury current. The geneses of these electrical alterations are briefly discussed. The possibility of an anaphylactic reaction at the level of the coronary arterial wall, previously mentioned in the literature, seems unlikely. The role of the haemodynamic changes and of the increased right ventricular blood pool is thought to be predominant.     

In vitro hydrolysis of gliadin and casein peptides: secondary defect in coeliac disease shown by organ culture

The authors examined whether there is any correlation between the regression speed of cardiac beta (V3)-myosin heavy-chain (MHC) isozyme and duration of overload. The results showed that in the right ventricle of a 1-week overloaded group, the loaded ventricular MHC isozyme V3 (29 center dot 0 +/- 5 center dot 0%, P < 0 center dot 05) returned to the control level within 1 week after relief of overload (20 center dot 4 +/- 4 center dot 2%, P = NS), whereas in a 3 week overloaded group (32 center dot 8 +/- 5 center dot 3%, P < 0 center dot 05) it took 10 weeks (36 center dot 6 +/- 8 center dot 6%, P = NS). The left ventricle showed the same tendency as the right ventricle. In sham-operated rats, however, the changes in MHC isozyme V3 in the left ventricle were greater than those in the right ventricle. These results suggest that regression speed of the cardiac MHC isoform, changed by pressure overload, is accompanied by the duration of overload. Furthermore, the right and left ventricles may have different responsiveness to MHC isoform transitions in heart stresses.     

Small genes/gene-products in Escherichia coli K-12

OBJECTIVE: We tested the hypothesis that right heart failure during endotoxin shock may result from altered ventriculovascular coupling responsible for impeding power transfer to the pulmonary circulation. METHODS: The changes in vascular pulmonary input impedance and right ventricular contractility produced by low-dose endotoxin infusion were studied in 6 intact anesthetized dogs. RESULTS: Endotoxin insult resulted in pulmonary hypertension (from 22 +/- 2 to 33 +/- 3 mmHg) associated with significant decreases in stroke volume (from 26.9 +/- 4 to 20.2 +/- 3 ml) and right ventricular ejection fraction (from 41 +/- 3 to 32 +/- 2%). The first minimum of input impedance spectrum and zero phase were shifted towards higher frequencies. Input resistance and characteristic resistance were dramatically increased. The latter change contributed to a significant increase in the pulsatile component of total right ventricular power output from 13 to 21%, indicating a reduction in the hydraulic right ventricle power output delivered into the main pulmonary artery. Overall changes in input pulmonary impedance were indicative of increased afterload facing the right ventricle leading to depressed performance. In contrast, right ventricular systolic elastance was simultaneously increased from 0.56 to 0.93 mmHg/ml indicating an increase in right heart contractility. CONCLUSION: These data suggest that pulmonary hypertension in the setting of experimental endotoxin shock is accompanied by deleterious changes in the pulmonary impedance spectrum, which are responsible for a mismatch of increased contractile state of the right ventricle to the varying hydraulic load ultimately leading to ventricular-vascular uncoupling.     

Vascular and cardiac remodeling in world class professional cyclists

BACKGROUND: Numerous studies have demonstrated that left ventricular (LV) hypertrophy is often associated with conditioning. METHODS AND RESULTS: The aim of the study was to evaluate cardiac and carotid artery changes induced by professional cycling. We collected M-mode left ventricle and B-mode right common carotid artery data from 149 male professional cyclists before the 1995 "Tour de France" race and 52 male control subjects. LV mass indexed to body surface area in cyclists was double that in control subjects, with no overlap of 95% confidence intervals (cyclists 100.9 to 187 g/m2 and control subjects 51.8 to 96.3 g/m2). Both mean arterial diameter and mean arterial diastolic intima-media thickness (IMT) were 13% higher in cyclists than in control subjects, with overlap of 95% confidence intervals (for arterial IMT 0.45 to 0.65 mm in cyclists and 0.38 to 0.60 mm in control subjects). CONCLUSIONS: Our results suggest that intense cycling has an effect on the cardiovascular system, more pronounced on the left ventricle and less pronounced on large arteries. Nevertheless, athletic training should be considered as a potential determinant of carotid modification.     

Calcium transients in single myocytes and membranous ultrastructures during the development of cardiac hypertrophy and heart failure in rats

1. We examined changes in intracellular calcium transients of separated single myocytes from the right ventricle (RV) of the rat heart during the change from adaptation to maladaptation in response to a pressure overload. 2. Right ventricular hypertrophy (RVH) secondary to pulmonary hypertension was induced by a subcutaneous injection of monocrotaline. Developed tensions of the RV-free wall were decreased as RVH progressed. Single myocytes were separated from the RV during different stages of RVH. Fura-2/AM-loaded cells were field stimulated, and changes in calcium transients were measured by Olympus OSP-3 system. We also examined membranous ultrastructures (sarcoplasmic reticulum, mitochondria, surface caveolae) involved in calcium metabolism in the hearts using scanning electron microscopy. 3. We observed characteristic changes in calcium transients during the change from adaptation to maladaptation, and also found that one parameter (amplitude) of calcium transients appeared to be correlated with the changes in the number of sarcoplasmic reticulum. 4. These results provided some insights into the mechanism of calcium handling of hypertrophied heart in response to a pressure overload from adaptation to maladaptation especially when stimulatory frequency was high, and suggested that heart rate control is a very important factor for the treatment of patients with congestive heart failure.     

Right latissimus dorsi cardiomyoplasty augments left ventricular systolic performance

We hypothesized that the right latissimus dorsi cardiomyoplasty augments left ventricular performance. Five dogs underwent staged right latissimus dorsi cardiomyoplasty. Ventricular function was studied 1 to 3 weeks later. Left ventricular pressure was measured with a micromanometer and left ventricular dimensions with piezoelectric crystals. Inferior vena caval occlusion was used to vary preload. Pressure-volume data were collected with the muscle unstimulated and stimulated at 1:2 and 1:1 muscle/heart ratios. The end-systolic pressure-volume relation (mm Hg/mL), stroke work, preload recruitable stroke work, left ventricular end-diastolic volume, and the diastolic relaxation constant were calculated and expressed as mean +/- standard deviation. Stimulated beats at a 1:2 ratio showed an increase in stroke work of 42.1% (978 +/- 381 to 1,390 +/- 449 g.cm; p < 0.01) and preload recruitable stroke work of 28.8% (59.4 +/- 20.7 to 76.6 +/- 11.0 g.cm/cm3; p = 0.05) compared with the unstimulated beats. With the stimulator on at 1:1, smaller changes occurred: stroke work increased 9% (1,167 +/- 390 to 1,273 +/- 363 g.cm; not significant) and preload recruitable stroke work increased 27% (63.9 +/- 22.7 to 80.9 +/- 23.1 g.cm/cm3; p = 0.05). There were no significant changes in the end-systolic pressure-volume relation. The diastolic relaxation constant did not change at 1:1 (36 +/- 9.7 to 37 +/- 6.4 ms; not significant) or 1:2 (36 +/- 9.3 to 39 +/- 8.2 ms; not significant). Left ventricular end-diastolic volume was unchanged at 1:1 (34 +/- 10.7 to 32 +/- 10.3 mL) and at 1:2 (31 +/- 9.0 to 32 +/- 8.7 mL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Normalization of cardiac structure and function after regression of cardiac hypertrophy

Previous studies have shown regression of left ventricular hypertrophy after pharmacologic treatment of hypertensive patients; however, the impact of regression of left ventricular hypertrophy on systolic function and on left and right ventricular diastolic function remains controversial and is difficult to assess because previous studies have not included concurrently studied age-matched control groups. Left ventricular mass, systolic function, and left and right ventricular diastolic function were assessed in 27 hypertensive patients, aged 43 +/- 6 years, by echocardiographic and Doppler studies before and 1, 3, 5, and 7 months after treatment. Left ventricular mass and ventricular function were concurrently evaluated in 27 age-matched normotensive subjects. Treatment with antihypertensive agents resulted in a significant (p < 0.001) reduction in diastolic blood pressure of 15 mmHg, measured at 1 month and sustained throughout the study. In response to hemodynamic unloading, left ventricular mass index decreased from 129 +/- 30 gm/m2 at baseline to 105 +/- 26 (p < 0.05) and 88 +/- 14 gm/m2 (p < 0.05) at 1 and 3 months of treatment, respectively, and remained unchanged over the subsequent 4 months. After 3 months of treatment, left ventricular mass index was similar in treated hypertensive and control subjects. Systolic function, assessed in terms of the relationship between shortening fraction and end-systolic wall stress, was unchanged throughout the treatment period and was no different from that in control subjects. However, patients with an initially depressed shortening fraction experienced a greater increase in shortening fraction during treatment compared to those with an initially normal shortening fraction (11% +/- 4% vs 5% +/- 5%, p < 0.01) and showed an improvement in the relationship between shortening fraction and end-systolic wall stress during treatment. Ventricular filling dynamics improved during the first 3 months of treatment, after which they were unchanged. Ventricular filling dynamics were similar in treated hypertensive patients and control subjects. In conclusion, sustained hemodynamic unloading of the left ventricle results in normalization of left ventricular mass, systolic function, and left and right ventricular diastolic filling dynamics, compared to those in age-matched control subjects.