Desenvolvimento do omaso de bovinos da raça Nelore (Bos taurus indicus) durante o período pré-natal

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A naturally shaped silicone ventricle evaluated in a mock circulation loop : a preliminary study

Mock circulation loops are used to evaluate the performance of cardiac assist devices prior to animal and clinical testing. A compressible, translucent silicone ventricle chamber that mimics the exact size, shape and motion of a failing heart is desired to assist in flow visualization studies around inflow cannulae during VAD support. The aim of this study was therefore to design and construct a naturally shaped flexible left ventricle and evaluate its performance in a mock circulation loop. The ventricle shape was constructed by the use of CT images taken from a patient experiencing cardiomyopathic heart failure and used to create a 3D image and subsequent mould to produce a silicone ventricle. Different cardiac conditions were successfully simulated to validate the ventricle performance, including rest, left heart failure and VAD support.

Phosphodiesterase PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

Background and purpose Phosphodiesterases PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3-1μM) or PDE4 inhibitor rolipram (1-10μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1Hz. The effects of (-)-noradrenaline, mediated through β1-adrenoceptors (β2-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2-adrenoceptors (β1-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P=0.037) of the positive inotropic effects of (-)-adrenaline (0.78±0.12 log units) than (-)-noradrenaline (0.47±0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1- and β2-adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2-adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle.

MRI-based strain and strain rate analysis of left ventricle: A modified hierarchical transformation model

Background Different from other indicators of cardiac function, such as ejection fraction and transmitral early diastolic velocity, myocardial strain is promising to capture subtle alterations that result from early diseases of the myocardium. In order to extract the left ventricle (LV) myocardial strain and strain rate from cardiac cine-MRI, a modified hierarchical transformation model was proposed. Methods A hierarchical transformation model including the global and local LV deformations was employed to analyze the strain and strain rate of the left ventricle by cine-MRI image registration. The endocardial and epicardial contour information was introduced to enhance the registration accuracy by combining the original hierarchical algorithm with an Iterative Closest Points using Invariant Features algorithm. The hierarchical model was validated by a normal volunteer first and then applied to two clinical cases (i.e., the normal volunteer and a diabetic patient) to evaluate their respective function. Results Based on the two clinical cases, by comparing the displacement fields of two selected landmarks in the normal volunteer, the proposed method showed a better performance than the original or unmodified model. Meanwhile, the comparison of the radial strain between the volunteer and patient demonstrated their apparent functional difference. Conclusions The present method could be used to estimate the LV myocardial strain and strain rate during a cardiac cycle and thus to quantify the analysis of the LV motion function.

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.

Left ventricle functional analysis from coronary CT angiography

Coronary CT angiography is widely used in clinical practice for the assessment of coronary artery disease. Several studies have shown that the same exam can also be used to assess left ventricle (LV) function. LV function is usually evaluated using just the data from end-systolic and end-diastolic phases even though coronary CT angiography (CTA) provides data concerning multiple cardiac phases, along the cardiac cycle. This unused wealth of data, mostly due to its complexity and the lack of proper tools, has still to be explored in order to assess if further insight is possible regarding regional LV functional analysis. Furthermore, different parameters can be computed to characterize LV function and while some are well known by clinicians others still need to be evaluated concerning their value in clinical scenarios. The work presented in this thesis covers two steps towards extended use of CTA data: LV segmentation and functional analysis. A new semi-automatic segmentation method is presented to obtain LV data for all cardiac phases available in a CTA exam and a 3D editing tool was designed to allow users to fine tune the segmentations. Regarding segmentation evaluation, a methodology is proposed in order to help choose the similarity metrics to be used to compare segmentations. This methodology allows the detection of redundant measures that can be discarded. The evaluation was performed with the help of three experienced radiographers yielding low intraand inter-observer variability. In order to allow exploring the segmented data, several parameters characterizing global and regional LV function are computed for the available cardiac phases. The data thus obtained is shown using a set of visualizations allowing synchronized visual exploration. The main purpose is to provide means for clinicians to explore the data and gather insight over their meaning, as well as their correlation with each other and with diagnosis outcomes. Finally, an interactive method is proposed to help clinicians assess myocardial perfusion by providing automatic assignment of lesions, detected by clinicians, to a myocardial segment. This new approach has obtained positive feedback from clinicians and is not only an improvement over their current assessment method but also an important first step towards systematic validation of automatic myocardial perfusion assessment measures.

Doppler vortography : detection and quantification of the vortices in the left ventricle

Nous proposons une nouvelle méthode pour quantifier la vorticité intracardiaque (vortographie Doppler), basée sur l’imagerie Doppler conventionnelle. Afin de caractériser les vortex, nous utilisons un indice dénommé « Blood Vortex Signature (BVS) » (Signature Tourbillonnaire Sanguine) obtenu par l’application d’un filtre par noyau basé sur la covariance. La validation de l’indice BVS mesuré par vortographie Doppler a été réalisée à partir de champs Doppler issus de simulations et d’expériences in vitro. Des résultats préliminaires obtenus chez des sujets sains et des patients atteints de complications cardiaques sont également présentés dans ce mémoire. Des corrélations significatives ont été observées entre la vorticité estimée par vortographie Doppler et la méthode de référence (in silico: r2 = 0.98, in vitro: r2 = 0.86). Nos résultats suggèrent que la vortographie Doppler est une technique d’échographie cardiaque prometteuse pour quantifier les vortex intracardiaques. Cet outil d’évaluation pourrait être aisément appliqué en routine clinique pour détecter la présence d’une insuffisance ventriculaire et évaluer la fonction diastolique par échocardiographie Doppler.

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.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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.

Fourth ventricle computed tomography indexes: standardisation and characteristics in neurocysticercosis

OBJETIVOS: propor padrão de normalidade das dimensões do IVventrículo e estudar suas características em neurocisticercose. MÉTODO: em um grupo controle (GC) constituído de 114 indivíduos com tomografias normais e em outro grupo composto de 80 doentes com neurocisticercose (GN), mediram-se a distância fronto-polar de ventrículos laterais (FP) e os diâmetros craniano interno (Cr), ântero-posterior (AP) e látero-lateral (LL) do IVº ventrículo para a padronização de seis índices. RESULTADOS: AP/Cr, AP/LL e AP/FP foram os índices mais discriminatórios e apresentaram, em GC, valores médios de 0,063, 0,267 e 0,582, respectivamente. em GN os valores foram estatisticamente superiores a GC. Selecionaram-se 51 doentes do GN com índice> ou =2 desvios-padrão da média em GC. Neles, AP/Ll foi> ou =1 em 95% doentes com derivação liquórica e em 88% com depressão, ocorrendo em 73% com evolução satisfatória e todos que faleceram. CONCLUSÃO: AP/Cr, AP/LL e, principalmente, AP/FP são representativos das dimensões do IVventrículo.

Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle

Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzmann rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 mug/mul) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 mug/mul) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 mug/mul) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/mul) injected into LV increased into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 mug/mul, isoproterenol produced and additive effect on pilocarpine-induced salivary secretion. The 40-nmol/mul dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/mul), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced and increase in salivary secretion. The 40-nmol/mul dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated. (C) 2002 Elsevier B.V. All rights reserved.