Physiological cardiac hypertrophy: critical role of AKT in the prevention of NHE-1 hyperactivity.

Background: The involvement of NHE-1 hyperactivity, critical for pathological cardiac hypertrophy (CH), in physiological CH has not been elucidated yet. Stimulation of NHE-1 increases intracellular Na(+) and Ca(2+) favouring calcineurin activation. Since myocardial stretch, an activator of NHE-1, is common to both types of CH, we speculate that NHE-1 hyperactivity may also happen in physiological CH.

Gender differences in cardiac left ventricular mass and function: Clinical and experimental observations.

Background: The aim of this study was to evaluate gender-associated impact on left ventricular mass (LVM) and on left ventricular function (LVF) in humans and rats with aging.

Methods: Myocyte area and collagen volume fraction (CVF) were studied in rats. LVM and LVF were evaluated in animals and humans by echocardiography and LVM index (LVMI) was obtained.

Sex-related difference in left ventricular mass in nonhypertensive young adults: role of arterial pressure.

Background: Blood pressure (BP) is higher in men than in women at similar ages through adult life. Interestingly, a similar pattern is detected in left ventricular mass (LVM), classically attributed to differences in body size. However, the existing difference in BP between sexes might be relevant in determining LVM and it has been not fully investigated.

In vivo key role of reactive oxygen species and NHE-1 activation in determining excessive cardiac hypertrophy.

Growing in vitro evidence suggests NHE-1, a known target for reactive oxygen species (ROS), as a key mediator in cardiac hypertrophy (CH). Moreover, NHE-1 inhibition was shown effective in preventing CH and failure; so has been the case for AT1 receptor (AT1R) blockers. Previous experiments indicate that myocardial stretch promotes angiotensin II release and post-translational NHE-1 activation; however, in vivo data supporting this mechanism and its long-term consequences are scanty.

[Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters.

Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively).

[Paradigms and paradoxes of left ventricular hypertrophy: from the research laboratory to the clinical consultation].

Cardiac hypertrophy can occur as an adaptative response to increased cardiac workload. Different types of cardiac hypertrophy arise from a combination of genetic, physiologic, and environmental factors. When hypertophic growth of the heart leads to left ventricular dysfunction and heart failure, the response is considered as maladaptive or pathological hypertrophy.

Normalization of the calcineurin pathway underlies the regression of hypertensive hypertrophy induced by Na+/H+ exchanger-1 (NHE-1) inhibition.

Na+/H+ exchanger-1 (NHE-1) inhibition induces cardiac hypertrophy regression and (or) prevention in several experimental models, although the intracellular events involved remain unclarified. We aimed to determine whether the calcineurin/NFAT pathway mediates this effect of NHE-1 inhibitors. Spontaneously hypertensive rats (SHR) with cardiac hypertrophy were treated with the NHE-1 inhibitors cariporide and BIIB723 for 30 days.

[Embolism predictors of infective endocarditis].

The embolic event (EE) increases the morbidity and mortality of infective endocarditis (IE). Prevalence of EE ranges between 22% and 50%, death rates being up to 25% of patients. EE may occur prior to diagnosis, during treatment or afterwards.

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction.

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition.

[Echocardiographic analysis of the effect of different Na+/H+ exchanger inhibitors on left ventricular structure and function in spontaneously hypertensive rats].

The aim of this study was to analyze by echocardiogram, the action of two Na+/H+ exchange, inhibitors, HOE 642 (HOE) and BIIB 723 (BIIB) on left ventricular (LV) mass and LV systolic function. We studied 16 spontaneously hypertensive rats (SHR), 8 treated with HOE 30 mg/kg/day, 8 with 30 mg/kg/day of BIIB during 30 days and 4 SHR as controls during those 30 days. Results are expressed as mean values +/- SEM.

The effect of xanthine oxidase inhibition upon ejection fraction in heart failure patients: La Plata Study.

Background: Reactive oxygen species (ROS) have been linked to hypertrophy, remodeling and abnormal excitation-contraction coupling. Previous data demonstrated that an increase in oxidative stress is associated to the pathogenesis of congestive heart failure (CHF). We examined whether inhibition of the superoxide anion (*O2(-))-generating enzyme xanthine oxidase (XO) with oxypurinol may improve cardiac function in patients with CHF.

Diagnostic role of new Doppler index in assessment of renal artery stenosis.

Background: Renal artery stenosis (RAS) is one of the main causes of secondary systemic arterial hypertension. Several non-invasive diagnostic methods for RAS have been used in hypertensive patients, such as color Doppler ultrasound (US). The aim of this study was to assess the sensitivity and specificity of a new renal Doppler US direct-method parameter: the renal-renal ratio (RRR), and compare with the sensitivity and specificity of direct-method conventional parameters: renal peak systolic velocity (RPSV) and renal aortic ratio (RAR), for the diagnosis of severe RAS.

Serum carboxyl-terminal propeptide of procollagen type I in exercise-induced left ventricular hypertrophy.

Background: Left ventricular hypertrophy (LVH) induced by exercise is considered to be a physiologic adaptive mechanism without fibrogenic hyperactivity, as occurs in pathologic hypertrophy.

Hypothesis: This study investigated serum markers of collagen synthesis and echo parameters of left ventricular diastolic function (LVdf) in 22 male athletes.

Methods: Twenty-two highly competitive male athletes (10 cyclists, 12 soccer players) were studied with full history, clinical examination, Doppler echocardiogram, and serum concentration of the carboxyl-terminal propeptide of collagen type I (PIP).

Echocardiographic assessment of left ventricular midwall mechanics in spontaneously hypertensive rats.

Aims: The present study was attempted to determine whether LV midwall mechanics yielded different conclusions about LV systolic function than the assessment of endocardial LV mechanics by echocardiography in spontaneously hypertensive rats (SHR).

Methods And Results: Thirty-six (18 Wistar normotensive (W), 18 [SHR]) anesthetized rats were studied with two-dimensional directed M-mode echocardiogram to analyze LV structure (LV diameter, left ventricular wall thickness and LV mass [LVM]) and LV function (endocardial shortening [ES] and midwall shortening [MS]). Measurements were made from three consecutive cardiac cycles on the M-mode tracings.

Myocardial hypertrophy of normotensive Wistar-Kyoto rats.

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.

Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition.

Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either alpha- or beta-adrenergic stimulation. Because an association between the Na+/H+ exchanger and cellular growth has been proposed, this study aimed to analyze the possible role of the antiporter in isoproterenol-induced cardiac hypertrophy. Isoproterenol alone (5 mg/kg IP once daily) or combined with a selective inhibitor of the Na+/H+ exchanger activity (3 mg x kg(-1) x d(-1) BIIB723) was given to male Wistar rats for 30 days.

Correlation between myocardial perfusion abnormalities detected with intermittent imaging using intravenous perfluorocarbon microbubbles and radioisotope imaging during high-dose dipyridamole stress echo.

Background: The clinical accuracy of myocardial contrast echocardiography (MCE) using intermittent harmonic imaging and intravenous perfluorocarbon containing microbubbles during dipyridamole stress has not been evaluated in a multicenter setting.

Hypothesis: The accuracy of dipyridamole stress contrast echo in the detection of coronary artery disease (CAD) using myocardial perfusion images is high in comparison with technetium-99 (99Tc) sestamibi single-photon emission computed tomography (MIBI SPECT) and increases the accuracy of wall motion data.

Methods: In 68 consecutive nonselected patients (46 men; mean age 66 years) from three different institutions in two countries.