Sildenafil for pulmonary hypertension treatment after cardiac surgery

Objective: To report on the use of sildenafil for pulmonary hypertension treatment of a newborn patient after cardiac surgery. Description: A female, full term newborn infant with diagnosis of double outlet right ventricle, pulmonary hypoplasia and subaortic ventricular septal defect, was submitted to Blalock surgery in the first week of life. In postoperative the newborn had pulmonary hypertension and persistent hypoxia, without response to nitric oxide, but with improved oxygenation after continuous intravenous infusion of prostaglandin E1. After several failed attempts to discontinue prostaglandin E1, oral sildenafil was used. There was a decrease in pulmonary vascular resistance with consequent oxygenation improvement and 48 hours later it was possible to discontinue prostaglandin E1 infusion. Comments: Sildenafil can be an alternative therapy for pulmonary hypertension, especially when there is no response to conventional therapy. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Essential role of GATA5 in the mammalian heart

réalisé en cotutelle avec le Dr. Marie Kmita et Dr. Marco Horb

Double-chambered right ventricle in an adult patient diagnosed by transthoracic echocardiography

Abstract Background Double-chambered right ventricle is a rare congenital disease frequently misdiagnosed in the adult patient. An anomalous muscle band divides the right ventricle in two cavities causing variable degree of obstruction. Although echocardiography is considered a useful method for the diagnosis of this pathology in children, it has been recognized the transthoracic scanning limitation in adults. Case presentation A 29 year-old patient with double-chambered right ventricle presenting mild exercise intolerance referred for follow up of a known ventricular septal defect in whom a complete diagnosis was obtained based only on transthoracic two dimensional echocardiography without the needing of cardiac catheterization. Conclusion Based on non invasive echocardiographic diagnosis, patient was referred to surgical correction, which was completely successful.

Distinctive Profile of IsomiR Expression and Novel MicroRNAs in Rat Heart Left Ventricle

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that negatively regulate target gene expression through mRNA cleavage or translational repression. There is mounting evidence that they play critical roles in heart disease. The expression of known miRNAs in the heart has been studied at length by microarray and quantitative PCR but it is becoming evident that microRNA isoforms (isomiRs) are potentially physiologically important. It is well known that left ventricular (patho)physiology is influenced by transmural heterogeneity of cardiomyocyte phenotype, and this likely reflects underlying heterogeneity of gene expression. Given the significant role of miRNAs in regulating gene expression, knowledge of how the miRNA profile varies across the ventricular wall will be crucial to better understand the mechanisms governing transmural physiological heterogeneity. To determinine miRNA/isomiR expression profiles in the rat heart we investigated tissue from different locations across the left ventricular wall using deep sequencing. We detected significant quantities of 145 known rat miRNAs and 68 potential novel orthologs of known miRNAs, in mature, mature* and isomiR formation. Many isomiRs were detected at a higher frequency than their canonical sequence in miRBase and have different predicted targets. The most common miR-133a isomiR was more effective at targeting a construct containing a sequence from the gelsolin gene than was canonical miR-133a, as determined by dual-fluorescence assay. We identified a novel rat miR-1 homolog from a second miR-1 gene; and a novel rat miRNA similar to miR-676. We also cloned and sequenced the rat miR-486 gene which is not in miRBase (v18). Signalling pathways predicted to be targeted by the most highly detected miRNAs include Ubiquitin-mediated Proteolysis, Mitogen-Activated Protein Kinase, Regulation of Actin Cytoskeleton, Wnt signalling, Calcium Signalling, Gap junctions and Arrhythmogenic Right Ventricular Cardiomyopathy. Most miRNAs are not expressed in a gradient across the ventricular wall, with exceptions including miR-10b, miR-21, miR-99b and miR-486.

ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models

The right ventricle has become an increasing focus in cardiovascular research. In this position paper, we give a brief overview of the specific pathophysiological features of the right ventricle, with particular emphasis on functional and molecular modifications as well as therapeutic strategies in chronic overload, highlighting the differences from the left ventricle. Importantly, we put together recommendations on promising topics of research in the field, experimental study design, and functional evaluation of the right ventricle in experimental models, from non-invasive methodologies to haemodynamic evaluation and ex vivo set-ups.

Predictors of Right Ventricle Dysfunction After Anterior Myocardial Infarction

Background: Regardless significant therapeutic advances, mortality and morbidity after myocardial infarction (MI) are still high. For a long time, the importance of right ventricle (RV) function has been neglected. Recently, RV dysfunction has also been associated with poor outcomes in the setting of heart failure. The shape, location, and contraction conditions make the RV chamber assessment technically challenging.Methods: Our study identified clinical characteristics and left ventricle (LV) echocardiographic data performed 3-5 days after MI that could be associated with RV dysfunction (RV fractional area change [FAC] < 35%) 6 months after MI.Results: The RV dysfunction group consisted of 11 patients (RV FAC 29.4% +/- 5.2) and the no RV dysfunction group of 71 patients (RV FAC 43.7% +/- 5.1); (P < 0.001). Both groups presented the same baseline clinical characteristics. Left atrium (LA), interventricular septum (IVS), and left ventricular posterior wall (LVPW) were larger in RV dysfunction than in no RV dysfunction. Conversely, E wave deceleration time (EDT) was lower in RV dysfunction when compared with no RV dysfunction. Left atrium(adj) (adjusted by gender, age, infarct size, and body mass index) (odds ratio [OR], 1.22; confidence interval [CI], 1.016-1.47; P = 0.032), interventricular septum(adj) (OR, 1.49; CI, 1.01-2.23; P = 0.044), and E wave deceleration time(adj) (OR, 0.98; CI, 0.97-0.98; P = 0.029) assessed soon after MI predicted RV failure after 6-months.Conclusions: LV diastolic dysfunction, resulting from anterior MI and assessed 3-5 days after the event, may play an important role in predicting RV dysfunction 6 months later.

Cardiac Magnetic Resonance Imaging: What Can It Add to Our Knowledge of the Right Ventricle in Pulmonary Arterial Hypertension?

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular remodeling leading to a progressive increase in pulmonary vascular resistance (PVR). It is becoming increasingly recognized that it is the response of the right ventricle (RV) to the increased afterload resulting from this increase in PVR that is the most important determinant of patient outcome. A range of hemodynamic, structural, and functional measures associated with the RV have been found to have prognostic importance in PAH and, therefore, have potential value as parameters for the evaluation and follow-up of patients. If such measures are to be used clinically, there is a need for simple, reproducible, accurate, easy-to-use, and noninvasive methods to assess them. Cardiac magnetic resonance imaging (CMRI) is regarded as the "gold standard" method for assessment of the RV, the complex structure of which makes accurate assessment by 2-dimensional methods, such as echocardiography, challenging. However, the majority of data concerning the use of CMRI in PAH have come from studies evaluating a variety of different measures and using different techniques and protocols, and there is a clear need for the development of standardized methodology if CMRI is to be established in the routine assessment of patients with PAH. Should such standards be developed, it seems likely that CMRI will become an important method for the noninvasive assessment and monitoring of patients with PAH. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110[suppl]:25S-31S)

Echocardiogram versus cardiac magnetic resonance imaging for assessing systolic function of subaortic right ventricle in adults with complete transposition of great arteries and previous atrial switch operation

In adults with congenital heart disease and a systemic right ventricle, subaortic ventricular systolic dysfunction is common. Echocardiographic assessment of systolic right ventricular (RV) function in these patients is important but challenging. The aim of the present study was to assess the reliability of conventional echocardiographic RV functional parameters to quantify the systolic performance of a subaortic right ventricle. We compared 56 contemporary echocardiograms and cardiac magnetic resonance studies in 37 adults, aged 26.9 ± 7.4 years, with complete transposition and a subaortic right ventricle. The fractional area change (FAC), lateral tricuspid annular plane systolic excursion, lateral RV systolic motion velocities by tissue Doppler, RV myocardial performance index, and the rate of systolic RV pressure increase (dp/dt) measured across the tricuspid regurgitant jet were assessed by echocardiography and correlated with the cardiac magnetic resonance-derived RV ejection fraction (EF). The mean RVEF was 48.0 ± 7.8%. FAC (r(2) = 0.206, p = 0.001) and dp/dt (r(2) = 0.173, p = 0.009) significantly correlated with RVEF, and the other nongeometric echocardiographic parameters failed to show a significant correlation with RVEF by linear regression analysis. FAC <33% and dp/dt <1,000 mm Hg/s identified a RVEF of <50% with a sensitivity of 77% and 69% and a specificity of 58% and 87%, respectively. In conclusion, in patients with a systemic right ventricle, routine nongeometric echocardiographic parameters of RV function correlated weakly with cardiac magnetic resonance-derived EF. RV FAC and the measurement of the rate of systolic RV pressure increase (dp/dt) should be preferentially used to assess systemic systolic function in adult patients with a subaortic right ventricle.

Metabolic Disturbances in Male Broilers of Different Strains. 1. Performance, Mortality, and Right Ventricular Hypertrophy

Two trials were carried out to test the susceptibility for metabolic disturbances of different strains of male broilers. In Trial 1, 1,890 male chickens were allotted in a randomized block design with seven treatments (Arbor Acres, Avian Farms, Cobb-500, Hubbard-Peterson, ISA, Naked Neck, and Ross) and six blocks of 45 chickens. Trial 2 involved 2,184 male chickens of six strains (Arbor Acres, Avian Farms, Cobb 500, Hubbard-Peterson, ISA Naked Neck, and Ross) allotted in seven complete blocks of 52 birds. The same management system was adopted for all birds, reared up to 42 d in an open house during late winter (Trial 1) or late autumn (Trial 2). The most marked differences observed among the strains tested was the lower BW and higher feed conversion of Naked Neck broilers. Total percentage mortalities were high among the most productive broilers, being more than 50% due to sudden death (SDS) and ascites syndrome (AS). No Naked Neck birds died as a consequence of these disturbances and the total mortalities were significantly lower (P ≤ 0.05) than the other strains. The ratio of right ventricle weight to total ventricle weight of the dead birds was over 0.25, except for Naked Neck birds, which presented a nonhypertrophic ratio. The two trials confirmed the relationship between high productivity and high incidence of SDS and AS and indicated that Naked Neck male broilers are resistant to these metabolic disturbances.

Treatment of pulmonary thromboembolism in patients with systemic blood pressure stability and right ventricular dysfunction

Pulmonary thromboembolism (PTE) ranges from incidental, clinically unimportant thromboembolism to massive embolism with sudden death. Its treatment is well established in two groups of patients: heparin for those with normal systemic blood pressure without right ventricular dysfunction (RVD) and thrombolysis for those with RVD and circulatory shock. In an intermediate group of patients with systemic blood pressure stability combined with RVD, which is usually associated with worse outcome, the treatment is controversial. There are authors who strongly suggest thrombolysis while others contraindicate this procedure and recommend anticoagulation with heparin. This is a narrative review that includes clinical trials comparing thrombolysis and heparin for the treatment of PTE patients with systemic blood pressure stability and RVD published since 1973. The results show that there are only four trials on this subject with less than 500 patients. Many PTE patients with systemic blood pressure stability and RVD might benefit from thrombolysis but, on the other hand, the risk for hemorrhagic events may be increased. Large randomized clinical trials are required to clarify this. © 2008 Bentham Science Publishers Ltd.

Heart failure-induced skeletal myopathy in spontaneously hypertensive rats

Background: Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure. Methods: After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting. Statistical analysis: Student's t test and Pearson correlation. Results: All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615±412; SHR 2035±224 μm2; P < 0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform. Conclusion: Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure. © 2012 Elsevier B.V.

Non invasive assessment of right ventricle in patients with operated tetralogy of Fallot

The objective of this study was to evaluate right ventricular function in patients with right ventricular volume overload in patients with (tetralogy of Fallot, and pulmonary atresia + VSD ) underwent corrective surgery; with echocardiography measure that can be easily applied; and to study the relationship between ProBNP and the contractile function of the right ventricle, dilated right atrium, and the consequences of pulmonary insufficiency . Methods: The study included 50 patients (50% males, mean age 30.64 ± 13.30 years) with prior cardiac surgical intervention of TDF (90%) or pulmonary atresia + VSD (10%). (49 pz) have performed a cardiac MRI and clinical evaluation, (47 pz) echocardiogram, (48 pz) ECG, (34 pz) a cardiopulmonary exercise testing, (29 pz) a dosage of ProBNP. Results: The S-wave velocity (p <0.0001), the TAPSE (p <0.0001) correlated significantly with RVEF estimated by cardiac MRI. The VO2 max was 27.93 ± 12.91 ml / kg / min, 15% of patients had VE/VCO2 The peak> 35. ProBNP correlated positively and significantly with the area of the right atrium (p = 0.0001), and negative and significant with VO2 max (p = 0.04). Those who have increased pulmonary insufficiency (PVR fraction> 30%) have a significantly increased RVED volume (p = 0.01), reduced VO2 max (p = 0.04), and lower ejection fraction of LV (p = 0.02) than the group of patients with PVR ≤ 30. Conclusion: The TAPSE and S-wave velocity are fundamental and may become the technique of choice for routine assessment of RV systolic function in adult patients with TOF. The monitoring of the Pro BNP is probably a choice, given the simplicity and their information that correlate with the test cardiopulmonary. In view of the ventricular-ventricular interaction, so measures to maintain or restore the functioning of the pulmonary valve could preserve biventricular function.

Right ventricle best predicts the race performance in amateur ironman athletes

PURPOSE The ironman (IM) triathlon is a popular ultraendurance competition, consisting of 3.8 km of swimming, 180.2 km of cycling, and 42.2 km of running. The aim of this study was to investigate the predictors of IM race time, comparing echocardiographic findings, anthropometric measures, and training characteristics. METHODS Amateur IM athletes (ATHL) participating in the Zurich IM race in 2010 were included. Participants were examined the day before the race by a comprehensive echocardiographic examination. Moreover, anthropometric measurements were obtained the same day. During the 3 months before the race, each IM-ATHL maintained a detailed training diary. Recorded data were related to total IM race time. RESULTS Thirty-eight IM finishers (mean ± SD age = 38 ± 9 yr, 32 men [84%]) were evaluated. Total race time was 684 ± 89 min (mean ± SD). For right ventricular fractional area change (45% ± 7%, Spearman ρ = -0.33, P = 0.05), a weak correlation with race time was observed. Race performance exhibited stronger associations with percent body fat (15.2 ± 5.6%, ρ = 0.56, P = 0.001), speed in running training (11.7 ± 1.2 km · h(-1), ρ = -0.52, P = 0.002), and left ventricular myocardial mass index (98 ± 24 g · m(-2), ρ = -0.42, P = 0.009). The strongest association was found between race time and right ventricular end-diastolic area (22 ± 4 cm2, ρ = -0.64, P < 0.0001). In multivariate analysis, right ventricular end-diastolic area (β = -16.7, 95% confidence interval = -27.3 to -6.1, P = 0.003) and percent body fat (β = 6.8, 95% confidence interval = 1.1-12.6, P = 0.02) were independently predictive of IM race time. CONCLUSIONS In amateur IM-ATHL, RV end-diastolic area and percent body fat were independently related to race performance. RV end-diastolic area was the strongest predictor of race time. The role of the RV in endurance exercise may thus be more important than previously thought and needs to be further studied.

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequences

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequences

The conducting form of gramicidin A is a right-handed double-stranded double helix

The linear pentadecapeptide antibiotic, gramicidin D, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The x-ray crystal structures of the right-handed double-stranded double-helical dimers (DSDHℛ) reported here agree with 15N-NMR and CD data on the functional gramicidin D channel in lipid bilayers. These structures demonstrate single-file ion transfer through the channels. The results also indicate that previous crystal structure reports of a left-handed double-stranded double-helical dimer in complex with Cs+ and K+ salts may be in error and that our evidence points to the DSDHℛ as the major conformer responsible for ion transport in membranes.