Littérature scientifique sur le sujet « Ventricular chambers expansion »

A new experimental method for the evaluation of myocardial constitutive models combines magnetic resonance (MR) radiofrequency (RF) tissue-tagging techniques with iterative two-dimensional (2-D) nonlinear finite element (FE) analysis. For demonstration, a nonlinear isotropic constitutive model for passive diastolic expansion in the in vivo canine heart is evaluated. A 2-D early diastolic FE mesh was constructed with loading parameters for the ventricular chambers taken from mean early diastolic-to-late diastolic pressure changes measured during MR imaging. FE solution was performed for regional, intramyocardial ventricular wall strains using small-strain, small-displacement theory. Corresponding regional ventricular wall strains were computed independently using MR images that incorporated RF tissue tagging. Two unknown parameters were determined for an exponential strain energy function that maximized agreement between observed (from MR) and predicted (from FE analysis) regional wall strains. Extension of this methodology will provide a framework in which to evaluate the quality of myocardial constitutive models of arbitrary complexity on a regional basis.

✓ Six patients with severe intraventricular hemorrhage were treated with direct intraventricular infusion of urokinase. In each case, hemorrhage extended into all ventricular chambers, and a cast formation and expansion of the third and fourth ventricles were found. Immediately after the therapy was started (within 7 days from onset of symptoms), reduction of intraventricular hematoma volume was observed on computerized tomography. On average, both the third and fourth ventricles became clear on the third day after hemorrhage; there was one exception, a case of ruptured aneurysm. Five of the six patients showed excellent or good outcome, although two developed delayed hydrocephalus. No infection or rebleeding was observed. The outcome in a retrospectively studied group of five patients not treated with urokinase is also reported. The authors conclude that this relatively easy method of treatment will greatly improve the prognosis of severe intraventricular hemorrhage.

Coarctation of the aorta is a congenital malformation characterized by the presence of narrowing of the aorta, which can be localized in any part of it. In this publication, we present a clinical case of coarctation of the aorta before and after surgical correction in a newborn. The child was admitted to the cardiosurgical hospital at the age of 6 days. Congenital heart disease of a low category of complexity was diagnosed prenatally. After birth, the condition is satisfactory. After 3 hours, the negative dynamics due to the clinic of respiratory failure. According to echocardiography – hypoplasia of the aortic arch, coarctation of the aorta? Open ductus arteriosus, ventricular septal defect. On the 3rd day of life, a diagnosis of congenital pneumonia was made and the child was transferred to a cardiosurgical hospital. Upon admission to the FCSSH in Astrakhan, the condition was regarded as severe, due to heart and respiratory failure. The child is examined. On echocardiography – Pronounced preductal form of coarctation of the aorta. Hypoplasia of the proximal arch and isthmus. Open ductus arteriosus. Ventricular septal defect. biventricular hypertrophy. Severe dilatation of the right chambers of the heart. Relative hypoplasia of the left ventricle. Tricuspid regurgitation. On the 7th day of life, surgical correction of the defect was performed plasty of the arch and isthmus of the aorta, plasty of the VSD. The early postoperative period proceeded with a clinic of moderate respiratory and heart failure. Against the background of the expansion of the volume of feeding, chylothorax was detected, drainage of the right pleural cavity was prescribed. Enteral feeding has been replaced by parenteral nutrition. The child was extubated on the 4th postoperative day. However, oxygen dependence was noted. The pleural drainage was removed on the 11th day after the operation. On the 12th day, the newborn was transferred from the intensive care unit. Discharged from the hospital on the 20th day after surgical treatment. After 4 months the child was examined in the hospital. The general condition was regarded as satisfactory. This clinical example shows the complexity of prenatal diagnosis of obstructive pathology of the aortic arch and the rapid manifestation of clinical manifestations after birth against the background of an unfavorable combination with a large septal defect.

Platelet-activating factor (PAF) is a phospholipid mediator that induces cardiovascular collapse and release of the secondary mediator thromboxane A2 (TxA2). To clarify mechanisms involved in this collapse and, specifically, the relative contribution of left ventricular and right ventricular dysfunction, we studied 12 open-chest pigs. PAF infusion (0.04–0.28 nmol.kg-1.min-1) induced a 5- to 120-fold increase in pulmonary vascular resistance, a 75–98% fall in cardiac output, and systemic arterial hypotension. Right ventricular failure was indicated by chamber enlargement, decreased shortening, and increased right atrial pressures. In contrast, left ventricular dysfunction was accompanied by decreases in chamber dimensions and filling pressures that were unresponsive to volume expansion. U 46619 (a stable TxA2 analogue) and mechanical pulmonary artery constriction induced changes similar to PAF. In 11 additional closed-chest pigs, TxA2 blockade with indomethacin attenuated the PAF-induced rise in pulmonary vascular resistance, right ventricular dysfunction, and systemic hypotension. A specific TxA2 synthase inhibitor, OKY-046, also diminished hemodynamic effects of PAF in six other pigs. Tachyphylaxis was not observed in five pigs repeatedly given PAF. We conclude that acute right ventricular failure as the result of severe increase in pulmonary vascular resistance is the primary mechanism early in the course of PAF-induced shock in the pig. PAF-induced release of TxA2 may contribute significantly to these events.

Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure.

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

To establish whether coronary artery narrowing (CAN) in mice was accompanied by depressed ventricular function, tissue injury, and modifications in cardiac anatomy, the left coronary artery was constricted in FVB/N mice and the animals were killed 7 days later. CAN consisted of a 53% reduction in luminal diameter, which resulted in a twofold increase in left ventricular end-diastolic pressure. Left ventricular systolic pressure and left ventricular + and −dP/d t decreased 15, 21, and 11%, respectively. Left ventricular weight-to-body weight ratio increased 33%. This hypertrophic adaptation was characterized by a 9 and 20% increase in the longitudinal and transverse cavitary diameters, which provoked a 1.5-fold expansion in chamber volume. In contrast, wall thickness decreased 15%. These anatomic and functional changes induced a threefold elevation in diastolic stress. Foci of reparative fibrosis were found in the endomyocardium and epimyocardium, involving 2–3% of the tissue. Finally, myocyte loss in the ventricle was 15%, and myocyte hypertrophy was 38%. Impaired ventricular function, diastolic Laplace overloading, myocyte loss, and decompensated eccentric hypertrophy in mice after CAN mimic the ischemic cardiomyopathic heart in humans.

Obesity is a risk factor for heart failure and cardiovascular disease. Of particular note, over 80% of patients with heart failure with a preserved ejection fraction (HFpEF) are overweight or obese. In this study, we aimed to review the association between obesity and HFpEF. Obese patients with HFpEF exhibit a distinct phenotype. In addition to impaired left ventricular (LV) diastolic function and high filling pressures, obese patients with HFpEF possess other factors that cause elevated LV filling pressure, such as a greater dependence on plasma volume expansion, aggravated pericardial restraint, and increased ventricular interaction. Obesity can contribute to HFpEF through hemodynamic, neurohormonal, inflammatory, and mechanical mechanisms. An increased amount of body fat can induce plasma volume expansion, resulting in chamber remodeling, pericardial restraint, and ultimately elevations in LV filling pressure. Obesity can mediate the activation of sympathetic nervous system signaling and the renin-angiotensin-aldosterone system. These unique pathophysiological characteristics of individuals with both obesity and HFpEF suggest that obesity with HFpEF can be considered a specific phenotype. Future research is expected to clarify effective treatment modalities for obesity-related HFpEF.

Organ patterning during embryonic development requires precise temporal and spatial regulation of protein activity. microRNAs (miRNAs), small noncoding RNAs that typically inhibit protein expression, are broadly important for proper development, but their individual functions during organogenesis are largely unknown. We report that miR-138 is expressed in specific domains in the zebrafish heart and is required to establish appropriate chamber-specific gene expression patterns. Disruption of miR-138 function led to ventricular expansion of gene expression normally restricted to the atrio-ventricular valve region and, ultimately, to disrupted ventricular cardiomyocyte morphology and cardiac function. Temporal-specific knockdown of miR-138 by antagomiRs showed miR-138 function was required during a discrete developmental window, 24–34 h post-fertilization (hpf). miR-138 functioned partially by repressing the retinoic acid synthesis enzyme, aldehyde dehydrogenase-1a2, in the ventricle. This activity was complemented by miR-138-mediated ventricular repression of the gene encoding versican (cspg2), which was positively regulated by retinoic-acid signaling. Our findings demonstrate that miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway, and also establish the use of antagomiRs in fish for temporal knockdown of miRNA function.

La morphogenèse est un processus qui nécessite une régulation à plusieurs niveaux à la fois physique et génétique. Les perturbations de ce programme dans le contexte du cœur ont souvent des conséquences importantes sur l'organe, comme le prouve l’incidence de 1% des cardiopathies congénitales à la naissance. Les cardiopathies congénitales telles que les cardiomyopathies, affectent l’architecture du muscle cardiaque essentielle à sa fonction contractile. Les parois ventriculaires sont particulièrement importantes, à la fois pour définir la taille des lumières ventriculaires et pour établir une architecture de myofibre orientée, renforçant l’efficacité de la contraction. Des travaux antérieurs dans le laboratoire ont permis de mettre en évidence l’émergence de l’orientation du myocarde. L'analyse clonale a révélé que la croissance tissulaire orientée corrélait avec l'expansion des ventricules (Sigolène M. Meilhac et al., 2004) et préfigurait l’architecture des myofibres du cœur nouveau-né (Meilhac et al., 2003). L'analyse de l’architecture cellulaire a révélé une coordination locale des divisions cellulaires indiquant une orientation des divisions cellulaires (Le Garrec et al., 2013). Ces études suggèrent que la division cellulaire orientée joue un rôle important dans la formation du cœur. Cependant, les mécanismes par lesquels cela est régulé doivent encore être identifiés dans les ventricules embryonnaires. Dans ce projet, nous utilisons une combinaison d'approches transcriptomique, segmentation cellulaire 3D, traitements chimiques en culture d'embryons et interférence moléculaire pour, étudier un mécanisme de division cellulaire orientée. Par séquençage ARN des ventricules, nous avons identifié l’expression de composants de l’appareil NuMA: GPSM, de la voie de la polarité cellulaire planaire et de la voie de mécano-détection des intégrines, qui sont des voies candidates pour réguler l’orientation de la division cellulaire. En parallèle, nous avons voulu déterminer si les cellules des ventricules en expansion se comportaient conformément à la règle de Hertwig. Pour ce faire, nous avons mis en place une méthode d’imagerie de l’architecture cellulaire dans le cœur entier par transparisation CUBIC et microscopie tridimensionnelle à feuille de lumière. Nous avons également amorcé le développement d’une méthode automatique de segmentation pour quantifier les axes de division cellulaire dans les ventricules. En comparant l’axe d'élongation des cellules aux axes de division les outils et les approches décrite ci-dessus permettront de conclure s'il existe une coordination entre les deux. Pour analyser l'importance des contractions cardiaques sur la croissance orientée des ventricules, nous avons établi des conditions de culture d'embryons traités avec des perturbateurs pharmaceutiques de la contraction cardiaque. Les résultats préliminaires indiquent qu'une augmentation et une diminution du taux de contraction affectent la forme du cœur. Enfin, nous avons conçu des vecteurs pour cibler les trois voies mentionnées ci-dessus avec des protéines dominant négatives. Les résultats de cette recherche pourraient avoir des applications en ingénierie tissulaire pour la réparation du cœur
The development of the heart is an intricate process both physically and genetically which requires regulation on many levels. Perturbations of this cardiogenic programme often has potent consequence on the organ and this is evident from the 1% incidence in births which are affected by a congenital heart disease (CHD). CHDs, such as cardiomyopathies, affect the architecture of the cardiac muscle, which is vital to the heartsfunction. The shape of the ventricular walls is particularly important to their function in terms of both defining the shape of the ventricular chambers and in establishing an appropriate myofiber architecture for efficient contractions (Meilhac et al., 2003). Previous work in the lab has provided insight into how this is achieved in the ventricles. It was found, through clonal analysis, that oriented tissue growth underlies cardiac chamber expansion (Meilhac et al., 2004). Analysis of earlier stages of the embryonic heart found regional coordination of cell divisions which preconfigured the myofiber architecture of the adult heart (Le Garrec et al., 2013). These studies suggest that oriented cell division plays an important role in sculpting the heart. However a mechanism by which this is regulated has yet to be established in the expanding ventricular chambers. In this project we use a combination of transcriptomic analysis, 3D cell segmentation, embryo culture experiments and molecular interference to investigate a mechanism for oriented cell division. Using bulk RNAseq we identified the NuMA:GPSM apparatus, the Planar Cell Polarity pathway and the integrin mechano-sensing pathway as candidates for further analysis. In combination with the transcriptomic analysis we wanted to identify if cells in the expanding ventricles were behaving according to Hertwig’s rule. To do this we have established CUBIC clearing and three dimensional lightsheet microscopy along with an automatic cell segmentation method to quantify cell elongations in the cardiac chambers. By comparing the elongation ratio of the cell to the detected axes of division the tools and approaches described above will enable us to identify if coordination existed between the two and if this was regionally specific. To analyse the impact of cardiac contractions on oriented cell division we established embryo culture experiment conditions paired with pharmaceutical interference of contractions. Preliminary results indicate that both an increase and decrease of contraction rate affects the shape of the heart. Finally, we will target the three pathways mentioned above with dominant negative proteins in chimeric hearts to dissect the molecular pathways. The outcome of this research will have potential applications in tissue engineering therapies targeting the heart