Ventricular Chamber Research Articles

Ехокардіоґрафічна оцінка динаміки правошлуночкової функції у пацієнтів з гіпертонічною хворобою протягом медикаментозного лікування

Aim. Study the functional changes and assess the dynamics of the longitudinal kinetics of the right ventricular myocardium in patients with hypertensive heart disease on the background of treatment. Materials and Methods. It was included 30 patients with hypertensive heart disease second degree and diastolic dysfunction of left ventricle. Individualized treatment was chosen for patients to achieve a normal level of blood pressure during 6 months of study. Echocardiography was performed before the research and after 6 months of antihypertensive treatment. The standard measurements of left heart chambers were performed, left ventricular ejection fraction was measured by method biplane Simpson, left ventricular mass myocardial index was calculated. The sizes of the right ventricular chambers were obtained from apex four-chamber view. From this view index TAPSE was measured and diastolic function of both ventricles was assessed by pulse-wave Doppler imaging. The longitudinal myocardial kinetics of the left and right ventricles was assessed by pulse-wave tissue Doppler imaging, obtaining systolic (peak velocity Sm, contraction time СТm) and diastolic (early velocity Em, atrial velocity Am, ratio Em/Am, deceleration time DTEm and isovolumic relaxation time IVRTm) indexes. Ratio E/Em and tissue myocardial performance index MPIm were calculated. The dynamics of longitudinal right ventricular kinetics was analyzed after 6 months of antihypertensive treatment. Results and Discussion. In study group the mean age of patients was 55,5±5,8 years. Blood pressure before treatment was 161/103±17,9/10,8 mmHg, after 6 months of treatment - 134/83±9,4/7,8 mmHg respectively (p<0,001). The sizes of the left and right atriums, left ventricular myocardial mass index, right ventricular longitudinal size and wall were considerably decreased after treatment by the results of echocardiography. There wasn't significant dynamics of the TAPSE value. By the results of pulse-wave Doppler imaging the first type of diastolic dysfunction was predominated in 83% for the right ventricle. The right ventricular diastolic function improved in parallel with the positive changes in left ventricular diastolic filling after the treatment. Right ventricular early diastolic myocardial velocity Еm (from 0,08±0,013 m/s to 0,11±0,015 m/s, р<0,001) and ratio Em/Am (from 0,70±0,150 to 0,90±0,194, р<0,001) were significantly higher, deceleration time DTEm (from 162±52 ms to 131±37 ms, р <0,001) and isovolumic relaxation time IVRTm (from 26±23 ms to 16±13 ms, р<0,001) were significantly lower by the results of pulse-wave tissue Doppler imaging. Tissue myocardial performance index MPIm was significantly lower (from 0,31±0,117 to 0,25±0,069, р<0,001), that pointed to improvement of global longitudinal right ventricular myocardial kinetics. Reverse right ventricular remodeling under the influence of medicaments that suppress the renin-angiotensin-aldosterone system, helps to improve its diastolic function. Another possible pathogenetic mechanism is the improvement of the endothelial function of the blood vessels of the pulmonary circulation. Conclusions. Longitudinal diastolic function of the right ventricle is improved in patients with hypertensive heart disease after 6 months of antihypertensive treatment. There are the parallel changes of longitudinal right and left ventricular myocardium kinetics, assessed by pulse-wave tissue Doppler imaging, with lowering blood pressure. The indexes of the longitudinal right ventricular myocardium kinetics can be important criteria to assess the development of the early signs of heart failure and the influence of treatment on right ventricular dysfunction.

Нейрорадіологічна діагностика менінгіом серед первинних пухлин бічних шлуночків

Objective – to determine the main of neuroimaging characteristics meningiomas among primary tumors of the lateral ventricles. Materials and methods. The work is based on the analysis of a retrospective and prospective multicentric study. 275 history of disease patients with primary lateral ventricular tumors, among which 52 cases of the lateral ventricles meningiomas (LVM). Patients with LVM since 1990 to 2016 were treated in 6 neurosurgical institutions in Ukraine at SI «Romodanov Neurosurgery Institute NAMS of Ukraine» (n = 25, including 1 patient who was further operated in ^iv Regional Clinical Emergency Hospital), ^iv Regional Clinical Emergency Hospital (n = 13), Clinical Hospital «Feofaniya» (n = 5), Regional Clinical Hospital in Dnipro (n = 6), Uzhgorod (n = 3), Rivne (n = 1). All patients with a tumor of the lateral ventricle underwent magnetic resonance imaging (MRI) and computed tomography (CT) in standard modes, which were performed with a contrast. In the period since 1990 to 2000 CT was intended for all patients as the main method of diagnosis of this pathology, in the period since 1993 to 2016 – MRI. MRI allows to measure the tumor in three projections, identify adjacent structures located in close proximity to the tumor, and also provides images in the axial, coronary and sagittal sections. Results. According to CT and MRI data LVM were predominantly clearly delineated borders. In the anterior horn, meningiomas were localized in 2 (3.85 %) cases (one on the right and one on the left), in the trigone – in 22 (42.31 %o) cases (10 on the right and 12 on the left), in the posterior horn – in 20 (38.46 %) cases (8 on the right and 12 on the left). Less commonly in our study, neoplasms that spread beyond the limits of one ventricular chamber were detected: occupying the trigone within the left lateral ventricle with distribution in the temporal horn – 1 (1.92 %) case, occupying the frontal horn and the body of lateral ventricle – 2 (3.85 %) cases, both on the left. Also in establishing the preoperative diagnosis a cases of multiple meningiomas with great diagnostic value: in the area of the posterior horn on both side – 3 (5.77 %) cases (in one of which meningiomatosis was observed in the structure of the neurofibromatosis II), in the region of the anterior and posterior horns – 1 (1.92 %) case (in this patient individual meningeomas were located in the III and IV ventricles), the tumor occupying all the left ventricle from the frontal to the occipital horn, and another meningiomas occupying the occipital horn contralateral on the right side – 1 (1.92 %) case. Conclusions. Neuroimaging is important for determining the localization, structure, distribution and configuration of lateral ventricular tumors, involvement of adjacent structures. Careful study of CT/MRI images, taking into account age and general condition of patients (presence of concomitant diseases – neurofibromatosis, tuberous sclerosis, oncopathology of internal organs), allows at the preoperative diagnoses Identifying the histological type of tumor within the ventricle. Determination of specific features of the LVM according to neuroimaging allows to choose the optimal surgical access for each case.

Estimating left ventricular volume with ROI-based convolutional neural network

The volume of the human left ventricular (LV) chamber is an important indicator for diagnosing heart disease. Although LV volume can be measured manually with cardiac magnetic resonance imaging (MRI), the process is difficult and time-consuming for experienced cardiologists. This paper presents an end-to-end segmentation-free method that estimates LV volume from MRI images directly. The method initially uses Fourier transform and a regression filter to calculate the region of interest that contains the LV chambers. Then convolutional neural networks are trained to estimate the end-diastolic volume (EDV) and end-systolic volume (ESV). The resulting models accurately estimate the EDV and ESV with a mean absolute error of 15.83 and 9.82 mL, respectively, and an ejection fraction with root mean square error of 5.56%. The comparison results show that the direct estimation methods possess attractive advantages over the previous segmentation-based estimation methods.

Study of the Right Heart of High-Level African Adult Athletes: Electrocardiographic and Echocardiographic Aspects

Despite the growing interest in athlete’s right ventricle and various work carried out, many uncertainties are remaining. The interest of this work resides in the determination of the particularity in right heart of the black athlete subject. We conducted a prospective study from August to October 2016 in the cardiology department of Aristide Le Dantec University Hospital in Dakar. The included patients were divided according to the sporting practice as enduring, resistant and non-athletes. The parameters studied were electrocardiographic (atrial or ventricular hypertrophies), echocardiographic: dimensions of the right cavities, systolic and diastolic functions of the right ventricle. We included 58 subjects: 38 athletes including 28 endurance and 10 resistance and 20 non-athletes. The average age of the endurance athletes was 21.9 ± 3, 75 years, 26.30 ± 4.64 in resistance ones and 24.10 ± 1.89 in the non-athletic group. Two cases of first-degree atrioventricular block were recorded in athletes. On the echocardiographic point, the atrium surfaces, as well as the transverse diameter, were greater in athletes, especially in the endurance group. The mean diameters of the admission chamber and those of the right ventricular flush chamber were larger in the group of endurance athletes. It was the same for the annular and sagittal basal mean diameters of the RV as well as the RV/LV ratio. The anterior wall of the right ventricle was larger in athletes compared to non-athletes. The vena cava was greater in athletes, the pulmonary arterial pressure higher in resistance ones.

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs.

Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid1 also plays a major role in preventing DCM; however, the role of Tid1 in isoproterenol (ISO)-induced cardiac apoptosis and hypertrophy remains unclear. H9c2 cells were pretreated Tid1 before ISO-induced hypertrophy and apoptosis and then evaluated by IHC, TUNEL assay, IFC, Co-IP, and Western blot. From the IHC experiment, we found that Tid1 proteins were increased in tissues from different stages of human myocardial infarction. Using H9c2 cardiomyoblast cells we found that Tid1 was decreased by ISO treatment. However, over-expression of Tid1S suppressed NFATc3, BNP and calcineurin protein expression and inhibited NFATc3 nuclear translocation in ISO induced cardiomyoblast cells. On the other hand, Tid1S over-expression activated survival proteins p-AKTser473 and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid1 enhanced CHIP expression, and induced CHIP to ubiquitinate Gαs, resulting in increased Gαs degradation. Our study showed that Gαs is a novel substrate of CHIP, and we also found that the Tid1-CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.

A patient with Fontan physiology for laparoscopic cholecystectomy: A challenge for an anesthesiologist

Patients with a congenital single ventricular chamber, survives only because the systemic and pulmonary venous blood mixes. However such an arrangement has two major disadvantages of arterial desaturation and chronic volume overload to the single ventricle. In 1971, Francis Fontan from France, reported a new approach to the operative treatment of these malformations, separating the systemic and pulmonary circulations. The advancement of surgical techniques and medical management have resulted in greater than 90% survival rate of about 10 years after Fontan palliation. As a result, patients with Fontan physiology are increasingly presenting in the adult perioperative setting for various noncardiac surgeries. Understanding the Fontan physiology is essential for the successful anaesthetic management of these patients. We report a case of 22 year female with fontan physiology posted for elective laparoscopic cholecystectomy.

From 4D Medical Images (CT, MRI, and Ultrasound) to 4D Structured Mesh Models of the Left Ventricular Endocardium for Patient-Specific Simulations.

With cardiovascular disease (CVD) remaining the primary cause of death worldwide, early detection of CVDs becomes essential. The intracardiac flow is an important component of ventricular function, motion kinetics, wash-out of ventricular chambers, and ventricular energetics. Coupling between Computational Fluid Dynamics (CFD) simulations and medical images can play a fundamental role in terms of patient-specific diagnostic tools. From a technical perspective, CFD simulations with moving boundaries could easily lead to negative volumes errors and the sudden failure of the simulation. The generation of high-quality 4D meshes (3D in space + time) with 1-to-1 vertex becomes essential to perform a CFD simulation with moving boundaries. In this context, we developed a semiautomatic morphing tool able to create 4D high-quality structured meshes starting from a segmented 4D dataset. To prove the versatility and efficiency, the method was tested on three different 4D datasets (Ultrasound, MRI, and CT) by evaluating the quality and accuracy of the resulting 4D meshes. Furthermore, an estimation of some physiological quantities is accomplished for the 4D CT reconstruction. Future research will aim at extending the region of interest, further automation of the meshing algorithm, and generating structured hexahedral mesh models both for the blood and myocardial volume.

The transcription factor MEF2A fine-tunes gene expression in the atrial and ventricular chambers of the adult heart

The distinct morphological and functional properties of the cardiac chambers arise from an elaborate developmental program involving cell lineage determination, morphogenesis, and dynamic spatiotemporal gene expression patterns. Although a number of transcription factors have been identified for proper gene regulation in the chambers, the complete transcriptional network that controls these patterns remains poorly defined. Previous studies have implicated the MEF2C transcription factor in the regulation of chamber-restricted enhancers. To better understand the mechanisms of MEF2-mediated regional gene regulation in the heart, we took advantage of MEF2A knock-out (KO) mice, a model that displays a predominantly ventricular chamber phenotype. Transcriptomic analysis of atrial and ventricular tissue from adult MEF2A KO hearts revealed a striking difference in chamber gene expression, with a larger proportion of dysregulated genes in the atrial chambers. Canonical pathway analysis of genes preferentially dysregulated in the atria and ventricles revealed distinct MEF2A-dependent cellular processes in each cardiac chamber. In the atria, MEF2A regulated genes involved in fibrosis and adhesion, whereas in the ventricles, it controlled inflammation and endocytosis. Finally, analysis of transcription factor-binding site motifs of differentially dysregulated genes uncovered distinct MEF2A co-regulators for the atrial and ventricular gene sets, and a subset of these was found to cooperate with MEF2A. In conclusion, our results suggest a mechanism in which MEF2 transcriptional activity is differentially recruited to fine-tune gene expression levels in each cardiac chamber. This regulatory mechanism ensures optimal output of these gene products for proper physiological function of the atrial and ventricular chambers.

Maternal Obesity and Cardiac Development in the Offspring: Study in Human Neonates and Minipigs

ObjectivesThe aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term). BackgroundThe epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality. MethodsEchocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood. ResultsIn neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p = 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p = 0.001), cardiomyocyte nuclei (+28%; p = 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes. ConclusionsNeonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function.

FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice

Protein quality control in cardiomyocytes is crucial to maintain cellular homeostasis. The accumulation of damaged organelles, such as mitochondria and misfolded proteins in the heart is associated with heart failure. During the process to identify novel mitochondria-specific autophagy (mitophagy) receptors, we found FK506-binding protein 8 (FKBP8), also known as FKBP38, shares similar structural characteristics with a yeast mitophagy receptor, autophagy-related 32 protein. However, knockdown of FKBP8 had no effect on mitophagy in HEK293 cells or H9c2 myocytes. Since the role of FKBP8 in the heart has not been fully elucidated, the aim of this study is to determine the functional role of FKBP8 in the heart. Cardiac-specific FKBP8-deficient (Fkbp8−/−) mice were generated. Fkbp8−/− mice showed no cardiac phenotypes under baseline conditions. The Fkbp8−/− and control wild type littermates (Fkbp8+/+) mice were subjected to pressure overload by means of transverse aortic constriction (TAC). Fkbp8−/− mice showed left ventricular dysfunction and chamber dilatation with lung congestion 1week after TAC. The number of apoptotic cardiomyocytes was dramatically elevated in TAC-operated Fkbp8−/− hearts, accompanied with an increase in protein levels of cleaved caspase-12 and endoplasmic reticulum (ER) stress markers. Caspase-12 inhibition resulted in the attenuation of hydrogen peroxide-induced apoptotic cell death in FKBP8 knockdown H9c2 myocytes. Immunocytological and immunoprecipitation analyses indicate that FKBP8 is localized to the ER and mitochondria in the isolated cardiomyocytes, interacting with heat shock protein 90. Furthermore, there was accumulation of misfolded protein aggregates in FKBP8 knockdown H9c2 myocytes and electron dense deposits in perinuclear region in TAC-operated Fkbp8−/− hearts. The data suggest that FKBP8 plays a protective role against hemodynamic stress in the heart mediated via inhibition of the accumulation of misfolded proteins and ER-associated apoptosis.

Evaluation of the right and left ventricles: An integrated approach measuring the area, length, and width of the chambers in normal fetuses

The purpose of this study was to simultaneously measure with speckle tracking software the end-diastolic ventricular area (A), basal transverse width (BW), mid-chamber transverse width (MW), and basal-apical length (BAL) in normal fetuses and those with pathology. The 4-chamber view of the fetal heart was obtained in 200 control fetuses between 20 and 40weeks of gestation and in 9 third-trimester fetuses with heart malformations. The mean and standard deviation for the A, BW, MW, and BAL were computed from the control fetuses and Z scores computed from the 9 fetuses with cardiac malformations. The A, BAL, BW, and MW were correlated with 7 somatic and age-independent variables (R2 =.63-.85). The highest R2 values occurred for the head circumference, estimated fetal weight, and ultrasound mean gestational age (.82-.85). Z-score values and centiles from the 9 fetuses with cardiac malformations suggested that the A, BW, MW, and BAL were below or above the 5th and 95th centiles as expected for the corresponding ventricular pathology. This study reports an integrated approach to evaluate the end-diastolic size of the right and left ventricular chambers and demonstrated clinical utility in fetuses with cardiac malformations.

Novel echocardiographic method to assess left ventricular chamber stiffness and elevated end-diastolic pressure based on time-velocity integral measurements of pulmonary venous and transmitral flows.

The detection of increased left ventricular (LV) chamber stiffness may play an important role in assessing cardiac patients with potential but not overt heart failure. A non-invasive method to estimate it is not established. We investigated whether the echocardiographic backward/forward flow volume ratio from the left atrium (LA) during atrial contraction reflects the LV chamber stiffness. We studied 62 patients who underwent cardiac catheterization and measured their left ventricular end-diastolic pressure (LVEDP) and pressure increase during atrial contraction (ΔPa) from the LV pressure waveform. Using the echocardiographic biplane method of disks, we measured the LV volume change during atrial contraction indexed to the body surface area (ΔVa), and ΔPa/ΔVa was calculated as a standard for the LV operating chamber stiffness. Using pulsed Doppler echocardiography, we measured the time-velocity integral (TVI) of the backward pulmonary venous (PV) flow during atrial contraction (IPVA) and the ratio of IPVA to the PV flow TVI throughout a cardiac cycle (FPVA). We also measured the TVI of the atrial systolic forward transmitral flow (IA) and the ratio of the IA to the transmitral TVI during a cardiac cycle (FA) and calculated IPVA/IA and FPVA/FA. IPVA/IA and FPVA/FA were well correlated with ΔPa/ΔVa (r = 0.79 and r = 0.81) and LVEDP (r = 0.73 and r = 0.77). The areas under the ROC curve to discriminate LVEDP >18 mmHg were 0.90 for IPVA/IA and 0.93 for FPVA/FA. The FPVA/FA, the backward/forward flow volume ratio from the LA during atrial contraction, is useful for non-invasive assessments of LV chamber stiffness and elevated LVEDP.

Production of aldosterone in cardiac tissues of healthy dogs and with dilated myocardiopathy.

Background and Aim:Aldosterone is a hormone, belonging to the group of mineralocorticoids, mainly synthesized in the adrenal cortex, basically its function is to regulate blood pressure and sodium-potassium levels in the body; high levels of this hormone have harmful effects in the organism and mainly in the heart in chronic form. Dilated cardiomyopathy is a progressive disease of heart muscle that is characterized by ventricular chamber enlargement and contractile dysfunction, is one of the most common cardiac conditions in dogs of medium and large breeds. The aim of the study was to determine and quantify if a dog’s cardiac cells possess the capacity to synthesize aldosterone, as well as, the differences that appear between a healthy heart and with dilated myocardiopathy (DMC).Materials and Methods:Cardiac tissues were used from six healthy dogs and six with DMC. Enzyme-linked immunosorbent assay was performed to determine if the dog’s heart cells synthesized this mineralocorticoid in a similar way to rat, rabbit, and human tissues, as well as quantitative differences between the healthy heart and DMC.Results:In healthy dog hearts, aldosterone values were 62.5 pG for both the atria and right ventricle and 125 pG for the left ventricle. As for dog hearts’ with DMC, results were 125 pG in all four cavities.Conclusion:Both the healthy and DMC dog hearts produce aldosterone in all four cavities, observing that production increases in the atria and right ventricle of those hearts with DMC, as an intrinsic mechanism of cardiac remodeling.

Twenty-four Segment Transverse Ventricular Fractional Shortening: A New Technique to Evaluate Fetal Cardiac Function.

Because of various fetal and maternal disease states, this study was conducted to evaluate the fractional shortening of 24 transverse segments distributed from the base to the apex of the ventricular chambers. Two hundred control fetuses were examined between 20 and 40 weeks' gestation. The transverse displacement of the ventricular endocardium during the cardiac cycle was computed by using offline software. From the output of the analysis, 24 end-diastolic and end-systolic segments were measured from the base (segment 1) to the apex (segment 24) of the right and left ventricles, and the fractional shortening was computed: [(end-diastolic length - end-systolic length)/end-diastolic length] × 100. Examples of fetal cardiovascular abnormalities were selected to demonstrate the utility of this technique. The fractional shortening for each segment was independent of gestational age and fetal biometric measurements. There was no significant difference in fractional shortening for segments 1 to 5 between the right and left ventricles. However, the fractional shortening of the left ventricle was significantly greater (P < .0001) than that of the right ventricle for segments 6 to 24, suggesting that the mid and apical segments of the left ventricle have increased displacement toward the center of the chamber compared to the right ventricle. Fetuses with various cardiac structural abnormalities had abnormal fractional shortening values. The fractional shortening of 24 segments of the right and left ventricles provides a comprehensive method to examine the contractility of the ventricular chambers.

The protective effect of activating Nrf2 / HO-1 signaling pathway on cardiomyocyte apoptosis after coronary microembolization in rats

BackgroundMyocardial apoptosis is closely related to myocardial injury caused by coronary microembolization (CME).Nuclear factor erythroid 2-like (Nrf2) has been taken into account as an inhibitor of apoptosis in various tissues. Thus, this research aims to investigate which part Nrf2/HO-1 signaling pathway plays in myocardial apoptosis process following the effect of CME on rats.MethodsSeparate 40 rats then form them into a group of shame, a group of CME, a group of CME plus AAV-Nrf2(AAV-Nrf2 (CME) group) and a group of CME plus AAV-control (AAV-control (CME) group) stochastically and averagely. Rat CME was established by injecting into the left ventricular chamber, with or without pretreatment of adeno-associated virus Nrf2 (AAV-Nrf2). Echocardiological measurements, using Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) to stain, conducting Quantitative PCR in real time (RT-PCR) as well as Western blotting to evaluate the impacts of them functionally, morphologically and molecularly in CME.ResultsNrf2 decreased in cardiomyocytes after CME. Upregulation of Nrf2 inside an organism through AAV connect to improving the function of heart as well as attenuating myocardial apoptosis, following the restrain of proapoptotic mRNAs and proteins like caspase-3, caspase-9 and bax expressing as well as the increase of antiapoptotic mRNA and proteins like HO-1 and bcl-2 expressing.ConclusionActivation of Nrf2/HO-1 pathway can improve CME-induced cardiac dysfunction effectively and also reduce the myocardial apoptosis.

A Novel Histone Deacetylase (HDAC) Inhibitor Attenuates Cardiac Dysfunction in the Setting of Pressure Overload Heart Failure

Background: Histone deacetylases (HDACs) are a family of epigenetic regulator enzymes responsible for chromatin conformation and reversible protein acetylation. HDAC inhibitors have previously been shown to be cardioprotective in acute myocardial infarction and heart failure. HDAC inhibition is thought to attenuate cardiac remodeling and improve cardiac function by enhancing acetylation of sarcomeric proteins, suppressing autophagy and apoptosis, bolstering protective genes and inhibiting pro-inflammatory genes. Objective: We investigated the efficacy of a novel, orally active HDAC class I inhibitor, MRL-003, in a murine model of pressure overload induced heart failure. Methods and Results: All studies were performed in a fully blinded manner, data analysis was performed off site by independent statisticians, and data was only unblinded following completion of statistical analysis of all parameters. Mice (C57 BL6J) at age 8-10 weeks were subjected to transverse aortic constriction (TAC) to induce pressure overload heart failure. Cardiac function was monitored sequentially using echocardiography and terminal hemodynamic measurements were taken. At 3 weeks post-TAC 3 doses (10, 30, and 100 mg/kg/day) of MRL-003 were provided to the mice in a blinded manner in chow ad libitum for 13 weeks. MRL-003 (100 mg/kg/d) significantly improved left ventricular (LV) ejection fraction and LV chamber dimensions compared to TAC-vehicle. LV end-diastolic pressure (LVEDP) was significantly increased in the vehicle treated group compared to sham and there was no significant difference in LVEDP in mice treated with MRL-003 (100 mg/kg/d) compared to sham. Conclusion: HDAC inhibition with MRL-003 significantly improves cardiac function and remodeling in the setting of pressure overload heart failure. Further studies are warranted to assess the molecular changes associated with these functional improvements.

Development and maturation of the fibrous components of the arterial roots in the mouse heart.

The arterial roots are important transitional regions of the heart, connecting the intrapericardial components of the aortic and pulmonary trunks with their ventricular outlets. They house the arterial (semilunar) valves and, in the case of the aorta, are the points of coronary arterial attachment. Moreover, because of the semilunar attachments of the valve leaflets, the arterial roots span the anatomic ventriculo‐arterial junction. By virtue of this arrangement, the interleaflet triangles, despite being fibrous, are found on the ventricular aspect of the root and located within the left ventricular cavity. Malformations and diseases of the aortic root are common and serious. Despite the mouse being the animal model of choice for studying cardiac development, few studies have examined the structure of their arterial roots. As a consequence, our understanding of their formation and maturation is incomplete. We set out to clarify the anatomical and histological features of the mouse arterial roots, particularly focusing on their walls and the points of attachment of the valve leaflets. We then sought to determine the embryonic lineage relationships between these tissues, as a forerunner to understanding how they form and mature over time. Using histological stains and immunohistochemistry, we show that the walls of the mouse arterial roots show a gradual transition, with smooth muscle cells (SMC) forming the bulk of wall at the most distal points of attachments of the valve leaflets, while being entirely fibrous at their base. Although the interleaflet triangles lie within the ventricular chambers, we show that they are histologically indistinguishable from the arterial sinus walls until the end of gestation. Differences become apparent after birth, and are only completed by postnatal day 21. Using Cre‐lox‐based lineage tracing technology to label progenitor populations, we show that the SMC and fibrous tissue within the walls of the mature arterial roots share a common origin from the second heart field (SHF) and exclude trans‐differentiation of myocardium as a source for the interleaflet triangle fibrous tissues. Moreover, we show that the attachment points of the leaflets to the walls, like the leaflets themselves, are derived from the outflow cushions, having contributions from both SHF‐derived endothelial cells and neural crest cells. Our data thus show that the arterial roots in the mouse heart are similar to the features described in the human heart. They provide a framework for understanding complex lesions and diseases affecting the aortic root.

Multiple Roles of Pitx2 in Cardiac Development and Disease.

Cardiac development is a complex morphogenetic process initiated as bilateral cardiogenic mesoderm is specified at both sides of the gastrulating embryo. Soon thereafter, these cardiogenic cells fuse at the embryonic midline configuring a symmetrical linear cardiac tube. Left/right bilateral asymmetry is first detected in the forming heart as the cardiac tube bends to the right, and subsequently, atrial and ventricular chambers develop. Molecular signals emanating from the node confer distinct left/right signalling pathways that ultimately lead to activation of the homeobox transcription factor Pitx2 in the left side of distinct embryonic organ anlagen, including the developing heart. Asymmetric expression of Pitx2 has therefore been reported during different cardiac developmental stages, and genetic deletion of Pitx2 provided evidence of key regulatory roles of this transcription factor during cardiogenesis and thus congenital heart diseases. More recently, impaired Pitx2 function has also been linked to arrhythmogenic processes, providing novel roles in the adult heart. In this manuscript, we provide a state-of-the-art review of the fundamental roles of Pitx2 during cardiogenesis, arrhythmogenesis and its contribution to congenital heart diseases.

GW28-e0050 Assessment 2D and 3D global longitudinal Strain of abnormal LV myocardial deformation properties Using 3D Speckle-Tracking Echocardiography in young HCM

Hypertrophic cardiomyopathy (HCM) is a disease predisposes to unexplained left ventricular (LV) hypertrophy and dysfunction and non-dilated ventricular chambers associated unusual myocardial mechanics. The most serious complications of HCM is sudden death for young subclinical patients, thus,

Intracardiac light catheter for rapid scanning transmural absorbance spectroscopy of perfused myocardium: measurement of myoglobin oxygenation and mitochondria redox state.

Absorbance spectroscopy of intrinsic cardiac chromophores provides nondestructive assessment of cytosolic oxygenation and mitochondria redox state. Isolated perfused heart spectroscopy is usually conducted by collecting reflected light from the heart surface, which represents a combination of surface scattering events and light that traversed portions of the myocardium. Reflectance spectroscopy with complex surface scattering effects in the beating heart leads to difficulty in quantitating chromophore absorbance. In this study, surface scattering was minimized and transmural path length optimized by placing a light source within the left ventricular chamber while monitoring transmurally transmitted light at the epicardial surface. The custom-designed intrachamber light catheter was a flexible coaxial cable (2.42-Fr) terminated with an encapsulated side-firing LED of 1.8 × 0.8 mm, altogether similar in size to a Millar pressure catheter. The LED catheter had minimal impact on aortic flow and heart rate in Langendorff perfusion and did not impact stability of the left ventricule of the working heart. Changes in transmural absorbance spectra were deconvoluted using a library of chromophore reference spectra to quantify the relative contribution of specific chromophores to the changes in measured absorbance. This broad-band spectral deconvolution approach eliminated errors that may result from simple dual-wavelength absorbance intensity. The myoglobin oxygenation level was only 82.2 ± 3.0%, whereas cytochrome c and cytochrome a + a3 were 13.3 ± 1.4% and 12.6 ± 2.2% reduced, respectively, in the Langendorff-perfused heart. The intracardiac illumination strategy permits transmural optical absorbance spectroscopy in perfused hearts, which provides a noninvasive real-time monitor of cytosolic oxygenation and mitochondria redox state.NEW & NOTEWORTHY Here, a novel nondestructive real-time approach for monitoring intrinsic indicators of cardiac metabolism and oxygenation is described using a catheter-based transillumination of the left ventricular free wall together with complete spectral analysis of transmitted light. This approach is a significant improvement in the quality of cardiac optical absorbance spectroscopic metabolic analyses.