Prevalence and upper limit of cardiac hypertrophy in professional cyclists

The term athlete's heart refers to an increased left ventricular mass. Few studies have assessed the prevalence and normal upper limit of cardiac hypertrophy in highly trained cyclists and this was the aim of this study. A group of 40 professional road cyclists [mean age 26 (SD 3) years] who had participated in European competitions for 3–10 years, were evaluated at the beginning of the 1992–93 season. Evaluation included a clinical history and physical examination, one and two-dimensional echocardiography, 12-lead resting electrocardiogram and a graded exercise test. Determination of the left ventricular mass index (LVMI) was performed using Devereux's formula with correction for the body surface area. Systolic and diastolic blood pressure were measured at rest and at peak exercise. Of the group 23 cyclists (58%) presented a LVMI greater than 130 g · m^–2, 21 cyclists presented a diastolic ventricular thickness equal to or greater than 13 mm, with a superior limit of 19 mm; 3 cyclists presented asymmetrical septum hypertrophy; and the relationship between posterior wall and left ventricular diastolic radius was equal to or greater than 0.45 in 14 cases (35%). Electrocardiographic abnormalities of ST-T segment were seen in only 1 subject. No correlation was found between the degree of ventricular hypertrophy and arterial blood pressure. We concluded that these professional cyclists showed a high prevalence of cardiac hypertrophy (58%). The distribution of this hypertrophy was concentric in 20/33 and asymmetric in 3/23 of the subjects with left ventricular hypertrophy. The electrocardiograms were normal in 98% of the subjects.     

Cardiac structure and function in monozygotic twin pairs discordant for physical fitness.

Cross-sectional studies in athletes and untrained subjects suggest that exercise training induces adaptations in cardiac structure and function. However, the role of genetic variation on the results has largely been ignored in these studies. The purpose of this study was to investigate the effects of long-term volitionally increased physical activity on electrocardiographic and echocardiographic parameters in male monozygotic twin pairs discordant for physical activity and fitness. On the basis of the mailed questionnaires, a telephone interview, and the inclusion criteria, 12 pairs of young adult male monozygotic twins were recruited from a Finnish twin cohort. All subjects completed a maximal oxygen uptake (.VO2 (max)) test and electrocardiography and echocardiography studies. Nine pairs had at least 9% difference in .VO2(max) and were selected for further analysis and for a second echocardiography study. Twins were divided into the more (MAG) and less active group (LAG), according to their VO2(max). On average, MAG had 18% higher VO2(max) compared with LAG. In electrocardiography, MAG had 29% (P = 0.02) higher Cornell voltage and 37% (P = 0.01) higher right-side hypertrophy index. In echocardiography, no significant differences were observed between the groups, and left ventricular mass index was only 7% (P = 0.16) higher in MAG. These results show that the volitionally increased physical activity that has led to an 18% increase in cardiorespiratory fitness induces greater changes in electro- than echocardiographic parameters. Electrocardiographic changes were suggestive of left ventricular hypertrophy, and echocardiography showed a similar but statistically nonsignificant trend.     

Combination of contrast with stress echocardiography: A practical guide to methods and interpretation

Contrast echocardiography has an established role for enhancement of the right heart Doppler signals, the detection of intra-cardiac shunts, and most recently for left ventricular cavity opacification (LVO). The use of intravenously administered micro-bubbles to traverse the myocardial microcirculation in order to outline myocardial viability and perfusion has been the source of research studies for a number of years. Despite the enthusiasm of investigators, myocardial contrast echocardiography (MCE) has not attained routine clinical use and LV opacification during stress has been less widely adopted than the data would support. The purpose of this review is to facilitate an understanding of the involved imaging technologies that have made this technique more feasible for clinical practice, and to guide its introduction into the practice of the non-expert user.     

Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits

Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg x kg(-1) x day(-1)) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P = 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.     

Left ventricular hypertrophy in obese hypertensives: is it really eccentric? (An echocardiographic study)

In order to study left ventricular hypertrophy patterns in obese hypertensives, we examined 132 patients with essential hypertension by 2D, M-mode and Doppler echocardiography. The patients were classified in four comparable groups, corresponding to the values of Quetelet's body mass index (BMI) and grades of obesity. More obese hypertensives had on average larger left ventricles with thicker walls and larger left atria than less obese, or lean ones. Left ventricular mass increased significantly and progressively with advancing grades of obesity, but relative wall thickness (wall thickness/cavity size ratio) did not diminish. Doppler echocardiography revealed significantly higher prevalence of left ventricular diastolic dysfunction among obese than among lean hypertensives. In the second part of our study, we analyzed the subgroups defined by the severity of hypertension and the age of the patients. The correlation of the indices of left ventricular and left atrial hypertrophy with the BMI values was considerably better in the group of moderate than in the group of mild hypertension. The r values were 0.62 vs. 0.22 for left ventricular mass and 0.64 vs. 0.26 for left atrial dimension. The group of patients with severe hypertension was characterized by left ventricular cavity enlargement in correlation with increasing BMI values, but without corresponding left ventricular wall thickening. So called left ventricular "eccentricity index", as the reverse value of relative wall thickness, correlated well (r = 0.76) with the BMI values. The indices of left ventricular hypertrophy correlated with the BMI values slightly better in middle age groups than in the groups of the youngest (< or = 30 years) or the eldest (> or = 61 years) hypertensives. In conclusion, eccentric left ventricular hypertrophy does not seem to be a distinctive feature of hypertensive heart disease in obesity. There is only some tendency toward the "eccentricity" of left ventricular geometry which becomes more apparent in more severe forms of hypertension, especially in very obese persons.     

Cardiac abnormalities in patients with mitochondrial DNA mutation 3243A>G

Background

Tissues that depend on aerobic energy metabolism suffer most in diseases caused by mutations in mitochondrial DNA (mtDNA). Cardiac abnormalities have been described in many cases, but their frequency and clinical spectrum among patients with mtDNA mutations is unknown.

Methods

Thirty-nine patients with the 3243A>G mtDNA mutation were examined, methods used included clinical evaluation, electrocardiogram, Holter recording and echocardiography. Autopsy reports on 17 deceased subjects were also reviewed. The degree of 3243A>G mutation heteroplasmy was determined using an Apa I restriction fragment analysis. Better hearing level (BEHL_{0.5–4 kHz}) was used as a measure of the clinical severity of disease.

Results

Left ventricular hypertrophy (LVH) was diagnosed in 19 patients (56%) by echocardiography and in six controls (15%) giving an odds ratio of 7.5 (95% confidence interval; 1.74–67). The dimensions of the left ventricle suggested a concentric hypertrophy. Left ventricular systolic or diastolic dysfunction was observed in 11 patients. Holter recording revealed frequent ventricular extrasystoles (>10/h) in five patients. Patients with LVH differed significantly from those without LVH in BEHL_{0.5–4 kHz}, whereas the contribution of age or the degree of the mutant heteroplasmy in skeletal muscle to the risk of LVH was less remarkable.

Conclusions

Structural and functional abnormalities of the heart were common in patients with 3243A>G. The risk of LVH was related to the clinical severity of the phenotype, and to a lesser degree to age, suggesting that patients presenting with any symptoms from the mutation should also be evaluated for cardiac abnormalities.     

A novel mouse model of X-linked cardiac hypertrophy

We recovered a novel mouse mutant exhibiting neonatal lethality associated with severe fetal cardiac hypertrophy and with some adult mice dying suddenly with left ventricular hypertrophic cardiomyopathy. Using Doppler echocardiography, we screened surviving adult mice in this mutant line for cardiac hypertrophy. Cardiac dimensions were obtained either from two-dimensional images collected using a novel ECG-gated ultra-high-frequency ultrasound system or by traditional M-mode imaging on a clinical ultrasound system. These analyses identified, among the littermates, two populations of mice: those with apparent cardiac hypertrophy with hypercontractile function characterized by ejection fraction of 75-80%, and normal littermates with ejection fraction of 53-55%. Analysis of the ECG-gated two-dimensional cines indicated that the hypertrophy was of the nonobstructive type. Further analysis of heart-to-body weight ratio confirmed the ultrasound diagnosis of left ventricular hypertrophic cardiomyopathy. Histopathology showed increased ventricular wall thickness, enlarged myocyte size, and mild myofiber disarray. Ultrastructural analysis by electron microscopy revealed mitochondria hyperproliferation and dilated sarcoplasmic reticulum. Genome scanning using microsatellite DNA markers mapped the mutation to the X chromosome. DNA sequencing showed no mutations in the coding regions of several candidate genes on the X chromosome, including several known to be associated with left ventricular hypertrophic cardiomyopathy. These findings suggest that this mouse line may harbor a mutation in a novel gene causing X-linked cardiomyopathy.     

Tissue Doppler and strain imaging: anything left in the echo-lab?

Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures.     

Electrical Inhomogeneity in Left Ventricular Hypertrophy

Recent studies designed to assess the relationship between aortic compliance and heterogeneity of heart electrical activity has shown that hypertrophy aggravates repolarization disturbances in the myocardium. Numerous mechanisms of electrical instability and inhomogeneity associated with left ventricular hypertrophy are now under investigation. Most of the studies have been found to be focused on ventricular Gradient, QT dispersion, amplitudes of isointegral maps during ventricular repolarization, abnormally low-QRST areas, dispersion of the QT interval, and spatial QRS-T _angle. These studies point to marked repolarization abnormalities in left ventricular hypertrophy and the dispersion of the QT interval as a valuable index for inhomogeneity of repolarization and the subsequent heart rate variability. The heart rate-corrected QT dispersion and QT apex dispersion seem to be significantly longer in the patients with left ventricular hypertrophy than in normal individuals. The review study has also identified QRST isointegral map as a valuable technique in assessment of the electro-cardiac events in LVH.     

Respective impacts of aortic stenosis and systemic hypertension on left ventricular hypertrophy

It has been reported that 30-40% of patients with aortic stenosis are hypertensive. In such patients, the left ventricle faces a double (i.e. valvular and vascular) pressure overload, which results in subsequent wall volume hypertrophy. From a clinical standpoint, it is difficult to separate the respective contributions of aortic stenosis and systemic hypertension to left ventricular burden and patient's symptoms and thus to predict whether valve replacement would be beneficial. The objective of this theoretical study was therefore to investigate the relative effects of valvular and vascular afterloads on left ventricular hypertrophy. We used a ventricular-valvular-vascular mathematical model in combination with the Arts' model describing the myofiber stress. Left ventricular wall volume was computed for different aortic blood pressure levels and different degrees of aortic stenosis severity. Our simulations show that the presence of concomitant systemic hypertension has a major influence on the development of left ventricular hypertrophy in patients with aortic stenosis. These results also suggest that mild-to-moderate aortic stenosis has a minor impact on left ventricular wall volume when compared with hypertension. On the other hand, when aortic stenosis is severe, wall volume increases exponentially with increasing aortic stenosis severity and the impact of aortic stenosis on left ventricular hypertrophy becomes highly significant.     

Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.     

Outcome of coronary plaque burden: a 10-year follow-up of aggressive medical management

Estimation of left ventricular (LV) mass has both prognostic and therapeutic value independent of traditional risk factors. Unfortunately, LV mass evaluation has been underestimated in clinical practice. Assessment of LV mass can be performed by a number of imaging modalities. Despite inherent limitations, conventional echocardiography has fundamentally been established as most widely used diagnostic tool. 3-dimensional echocardiography (3DE) is now feasible, fast and accurate for LV mass evaluation. 3DE is also superior to conventional echocardiography in terms of LV mass assessment, especially in patients with abnormal LV geometry. Cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) are currently performed for LV mass assessment and also do not depend on cardiac geometry and display 3-dimensional data, as well. Therefore, CMR is being increasingly employed and is at the present standard of reference in the clinical setting. Although each method demonstrates advantages over another, there are also disadvantages to receive attention. Diagnostic accuracy of methods will also be increased with the introduction of more advanced systems. It is also likely that in the coming years new and more accurate diagnostic tests will become available. In particular, CMR and CCT have been intersecting hot topic between cardiology and radiology clinics. Thus, good communication and collaboration between two specialties is required for selection of an appropriate test.     

Chronic all-trans retinoic acid treatment prevents medial thickening of intramyocardial and intrarenal arteries in spontaneously hypertensive rats

There are in vitro data linking all-trans retinoic acid (atRA) with inhibition of hypertrophy and hyperplasia in cardiomyocytes, vascular smooth muscle cells, and fibroblasts. In the present study, we tested the hypothesis that chronic treatment with atRA may blunt the process of myocardial remodeling in spontaneously hypertensive rats (SHR). Four-week-old male SHR were treated with atRA (5 or 10 mg.kg-1.day-1) given daily for 3 mo by gavage; age- and sex-matched Wistar-Kyoto rats (WKY) and placebo-treated SHR served as controls. At the end of the treatment period, cardiac geometry and function were assessed by Doppler echocardiography. Histological examination and RIA were performed to evaluate medial thickening of intramyocardial and renal arteries, perivascular and interstitial collagen content, and atrial natriuretic peptide (ANP) and IGF-I in the heart, respectively. The novel finding of the present study is that atRA prevented hypertrophy of intramyocardial and intrarenal arteries and ventricular fibrosis. However, atRA treatment did not lower blood pressure or left ventricular weight and left ventricular weight-to-body weight ratio in SHR. atRA did not change cardiac geometry and function as assessed by Doppler echocardiography. atRA showed no influence on either ANP or IGF-I levels. In conclusion, the present study suggests that chronic atRA treatment prevents medial thickening of intramyocardial and intrarenal arteries and ventricular fibrosis during the development of hypertension. Left ventricular hypertrophy and cardiac geometry and function are not changed by atRA treatment.     

Heart failure: mechanisms of cardiac and vascular dysfunction and the rationale for pharmacologic intervention

Congestive heart failure is a complex clinical syndrome that has its basis in an abnormality of myocardial cell function resulting in impaired ventricular performance, exercise intolerance, and ventricular arrhythmias. The functional defect in myocardial performance may be related to alterations in receptor function, in regulatory proteins, or in biochemical mechanisms. Remodeling of the left ventricle has been observed to play an important role in the natural course of heart failure. The complex interplay between cellular elongation, reactive hypertrophy, and the influence of the change from ellipsoid to spheroidal shape of the left ventricle after acute myocardial infarction are just beginning to be understood. Prevention of this remodeling effect by pharmacologic intervention is being widely explored, although the mechanisms are poorly defined. Impedance to left ventricular ejection is also an important determinant of cardiac performance in heart failure. Constriction of arteriolar resistance vessels and reduction in compliance of arterial conductance vessels is a common manifestation of heart failure and may be under the influence of neural, hormonal, endothelial, and local regulatory factors. Increased tone of venous capacitance vessels contributes to a shift of blood centrally and to an increase in ventricular preload. Vasodilator drugs by relaxing the arterial, arteriolar, and venous vasculature result in a reduction in impedance and left ventricular afterload and a decrease in cardiac filling pressure and preload. Structural changes of hypertrophy and remodeling apparently contribute to the changes in resistance, compliance, and capacitance in the vasculature. Treatment of heart failure is aimed at relieving symptoms and prolonging life. Interventions to improve left ventricular function are critical to symptom relief. Vasodilators have been most effective for this purpose, and new positive inotropic drugs are being tested for efficacy. Long-term benefit may require interference with the myocardial and peripheral vascular remodeling processes that lead to progressive depression of ventricular performance. New insights into the cellular and subcellular mechanisms of this progression are critical to the development of innovative therapeutic strategies.     

Applications and limitations of end-systolic measures of ventricular performance

The usefulness of end-systolic measures of left ventricular performance as a load-independent method of assessing of ventricular contractility has been studied in intact, conscious dogs. The end-systolic pressure-chamber diameter (P-D) relation was shown to be linear, unaltered by preload changes, and shifted in a parallel fashion by inotropic stimulation, whereas the end-systolic pressure-volume relation appeared to increase in slope with increased contractility. A simplified measure of end-systolic relations that does not require measurement of chamber volume or diameter, the end-systolic pressure-wall thickness ( WTh ) relation, was also linear and shifted with acute changes in inotropic state. During regional ischemia, the regional end-systolic WTh relation also may provide a relatively load-independent means of detecting regional depression of myocardial contractility. With chronic pressure overload hypertrophy in dogs, the end-systolic P-D relation was markedly shifted upward and to the left, which indicates hyperfunction of the left ventricle; however, end-systolic wall stress-diameter relations were identical before and after the development of hypertrophy, which suggests that myocardial contractility was unaltered. These findings and clinical studies of mitral regurgitation imply that for assessing resting left ventricular contractility in certain chronic conditions, the use of wall stress rather than pressure may be appropriate in the end-systolic framework. Further experimental studies are needed in the intact circulation to better characterize end-systolic relations before their full potential in the clinical setting can be realized.     

Regression of cardiac hypertrophy with drug treatment in spontaneously hypertensive rats

Left ventricular hypertrophy is an important complication of essential hypertension. Some antihypertensive drugs have been shown to allow regression of cardiac hypertrophy, both in spontaneously hypertensive rats and in hypertensive patients. Recent results show that the agents which interfere with the functions of the sympathetic nervous system, converting enzyme inhibitors and calcium antagonists are effective in reducing arterial blood pressure and regression of left ventricular hypertrophy. The use of vasodilators and diuretics may under certain circumstances, however, even exacerbate cardiac hypertrophy. Regression of left ventricular hypertrophy in hypertension does not appear to depend solely on reduction of arterial blood pressure. Other factors seem to modulate the myocardial response to antihypertensive treatment. Included among these mechanisms are neural, humoral, haemodynamic and biochemical factors. The available experimental data further suggest that some functional derangements and biochemical changes associated with hypertrophy may be reversed by antihypertensive treatment. There is, however, insufficient experience with human subjects to determine whether a reduction in left ventricular mass is associated with lower incidences of heart failure or mortality than may be achieved by adequate blood pressure control alone.     

缬沙坦联合氨氯地平治疗高血压伴左心肥厚的疗效及对心功能的影响

目的:通过探讨缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者的疗效及对心功能的影响,为临床治疗提供依据。方法:选择2010年1月~2014年12月我院收治的高血压伴左心室肥厚患者共120例,按照随机数字表法随机分为观察组和对照组。对照组患者给予氨氯地平,观察组患者缬沙坦联合氨氯地平治疗,治疗6个月后,观察两组患者舒张压(DBP)、收缩压(SBP)、心率(HR)、室间隔厚度(IVST),左室后壁厚度(LVPWT)、左室舒张末期内径(LVDd)和左室重量指数(LVMI)。结果:治疗后,两组患者SBP、DBP和HR均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者SBP、DBP和HR均低于对照组,差异有统计学意义(P0.05)。治疗后,两组患者IVST、IVPWT、LVDd和LVMI均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者IVST、IVPWT、LVDd和LVMI均低于对照组,差异有统计学意义(P0.05)。结论:缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者,能够降低患者血压、逆转左心室肥厚,改善患者心功能,疗效优于氨氯地平单独治疗,值得临床推广应用。     

A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart

The 16 kDa adipokine leptin has been shown to exert direct hypertrophic effects on cultured cardiomyocytes although its role as an endogenous contributor to postinfarction remodeling and heart failure has not been determined. We therefore investigated the effect of leptin receptor blockade in vivo on hemodynamic function and cardiac hypertrophy following coronary artery ligation (CAL). Cardiac function and biochemical parameters were measured in rats subjected to 7 or 28 days of left main CAL in the presence and absence of a leptin receptor antibody. Animals subjected to an identical treatment in which the artery was not tied served as sham-operated controls. CAL produced myocardial hypertrophy, which was most pronounced 28 days postinfarction as demonstrated by increases in both left ventricular weight-to-body weight ratio and atrial natriuretic peptide gene expression, both of which were abrogated by leptin receptor antagonism. Leptin receptor blockade also significantly improved left ventricular systolic function, attenuated the increased left ventricular end-diastolic pressure, and reduced the expression of genes associated with extracellular matrix remodeling 28 days following CAL. In conclusion, the ability of a leptin receptor-neutralizing antibody to improve cardiac function offers evidence that endogenous leptin contributes to cardiac hypertrophy following CAL. The possibility exists that targeting the myocardial leptin receptor represents a viable and novel approach toward attenuating postinfarction remodeling.     

Echocardiographic features of pigs with spontaneous hypertrophic cardiomyopathy

Ultrasonography is one of the most common, noninvasive techniques used for cardiovascular diagnosis because it provides reliable information and enhances patient safety. Two-dimensional (2-D) and M-mode echocardiography is conducted to assess the severity and distribution of myocardial hypertrophy. Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease that has variable manifestations because interactions between the many facets of systolic and diastolic dysfunction of the heart are complex. The objective of the study reported here was to characterized clinical HCM in pigs. A commercial Vingmed (CFM-800) 3.25 MHz transducer was used to perform 2-D and M-mode echocardiography. Experimental pigs (about 100 kg in body weight) were anesthetized and positioned in left lateral recumbency. Echocardiographic images (2-D) were acquired in parasternal short-axis and long-axis views. The 2-D images provided M-mode under direct anatomic visualization. The pigs were sacrificed for pathologic study after echocardiographic examination. In typical HCM cases (n = 8), the interventricular septum thickness increased, the left ventricular (LV) end-systolic and end-diastolic dimensions decreased, and the left atrial dimensions and the indexes of systolic function, such as ejection fraction and velocity of fiber shortening, increased. The LV outflow tract narrowed, particularly when gross upper septal hypertrophy was evident. Moreover, systolic cranial motion (SCM) of the septal leaflet of the mitral valve was observed. Doppler evidence of mitral regurgitation often was associated with SCM. The echocardiographic findings from pigs with HCM resembled those from humans. Thus, porcine HCM may serve as a spontaneous animal model for the study of HCM in humans.     

Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats

We examined whether adrenomedullin, a vasoactive peptide expressed in the heart, modulates the increase in blood pressure, changes in systolic and diastolic function, and left ventricular hypertrophy produced by long-term administration of ANG II or norepinephrine in rats. Subcutaneous administration of adrenomedullin (1.5 microg.kg(-1).h(-1)) for 1 wk inhibited the ANG II-induced (33.3 microg.kg(-1).h(-1) sc) increase in mean arterial pressure by 67% (P < 0.001) but had no effect of norepinephrine-induced (300 microg.kg(-1).h(-1) sc) hypertension. Adrenomedullin enhanced the ANG II-induced improvement in systolic function, resulting in a further 9% increase (P < 0.01) in the left ventricular ejection fraction and 19% increase (P < 0.05) in the left ventricular fractional shortening measured by echocardiography, meanwhile norepinephrine-induced changes in systolic function were remained unaffected. Adrenomedullin had no effect on ANG II- or norepinephrine-induced left ventricular hypertrophy or expression of hypertrophy-associated genes, including contractile protein and natriuretic peptide genes. The present study shows that adrenomedullin selectively suppressed the increase in blood pressure and augmented the improvement of systolic function induced by ANG II. Because adrenomedullin had no effects on ANG II- and norepinephrine-induced left ventricular hypertrophy, circulating adrenomedullin appears to act mainly as a regulator of vascular tone and cardiac function.