Left ventricular pumping performance may be described by intraventricular pressure and volume variables, usually presented as a pressure-volume plot. However, on-line monitoring of left ventricular pressure and volume with high temporal resolution requires the use of an invasive catheter technique such as, for example, the conductance catheter method. On the other hand, the very invasiveness and complexity of this approach makes it less suitable for clinical use. It is then not surprising that there has been long-felt need to make the conductance method less invasive and attempts have been made to adjust the method to clinical demands and routine in order to extract more information from pressure-volume interplay and possibly translate relevant data to their non-invasive estimates. In the present studies, a standard five segmental conductance catheter was used in animal (pig) experiments. Segmental conductances were compared to global conductance. Since the mid-ventricular segment was shown to reflect global volume, which was also shown on theoretical basis, it was concluded that a single segmental catheter most probably could be used to estimate global left ventricular volume. Subsequently, a thin and flexible single segmental conductance catheter was constructed and applied to an animal (pig) experimental model. Results were reproducible and very few arrythmias were detected. At the next stage, left ventricular isovolumic phases were investigated using the standard conductance catheter method, as well as echocardiographically derived tissue velocity doppler. Conductance was shown to decrease during isovolumic contraction, and an adjustment method was proposed in order to account for the subsequent decrease in pressure-volume loop area. In separate experiments, the left ventricular pressure wave form during left ventricular systole was examined, and an algorithm was proposed to discriminate between the changes in afterload, preload and contractility. Results showed clearly discernible patterns of the respective load and contractility alternation. Finally, the left ventricular continuous area was monitored continuously during the entire cardiac cycle as a measure of left ventricular volume dynamics in normal subjects and three patients with left ventricular abnormalities using echocardiographic automatic boundary detection. The left ventricular area thus obtained was plotted against its first derivative, to form a flow-volume estimates loop, in accordance with the flow-volume examinations used in respiratory physiology. Data obtained from the abnormal ventricles were presented as flow-volume estimates loops, exemplifying the possible use of the method. / QC 20100922

The third ventricle region houses several neuroanatomical structures that are primary components of the human memory system, and provides pathways through which these brain regions communicate with critical regions of the frontal and medial temporal lobes. Archival data was obtained for 42 children with cerebellar or third ventricle tumors, and was examined for tumor and treatment related confounds. Children with third ventricle tumors were hypothesized to exhibit; 1) better performance on a measure of auditory attention, 2) greater impairment in learning across trials, 3) greater memory loss over a 20-minute delay, and 4) greater impairment across delayed memory tests than the cerebellar group. Children with third ventricle tumors demonstrated significantly better auditory attention, but greater impairments in verbal learning, and greater verbal memory loss following a 20-minute delay. In contrast, children with third ventricle tumors did not demonstrate significantly greater memory impairments across long delay memory tests.

No description available.

A proteomic procedure for analyzing mouse left ventricular collagen by mass spectrometry has been developed. The procedure involves a purification step that removes non-collagenous cellular components from the collagen extracellular matrix, a step that solubilizes the collagen in aqueous solvents before it is proteolytically digested for analysis with ESI-LCMS/MS. Collagen from healthy and lathrytic mice has been positively identified by applying the SEQUEST database search algorithm to spectra from the collagen prepared using this procedure. Analysis shows that the relative percentage of collagen peptides detected in lathrytic tissue is significantly greater than that of the healthy tissue. These preliminary results suggest that the percentage of cross-linked collagen is lower in the lathrytic tissue as indicated by the greater protein sequence coverage obtained for this tissue. This procedure lays the ground work for future experimentation that has the ability to allow for the identification and quantification of cross-linked peptides.

This study examined right-ventricular-pulmonary arterial (RV-PA) coupling and pulmonary vascular mechanics during acute exercise in 12 middle-aged men with a long-standing history of endurance training. Subjects underwent simultaneous right-heart catheterization and echocardiography, with measures obtained at steady state heart rates of 100, 130 and 150 beats/min. Subjects were highly trained and displayed RV remodeling of endurance-trained athletes. During exercise at 100 beats/min, systolic, diastolic, and mean pulmonary artery pressure increased significantly from rest, as did pulmonary capillary wedge pressure. The slope of pooled mean pulmonary pressure indexed to cardiac output was 1.436 mmHg⋅min-1⋅L-1 with a distensibility index of 0.112 ± 0.048 mmHg-1. The pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees) decreased from rest to exercise at 130 beats/min (P < 0.01). These results suggest that Ea:Ees becomes favourable for RV function during exercise, indicative of a pulmonary vasculature that is highly distensible and well matched to RV output.

This study examined right-ventricular-pulmonary arterial (RV-PA) coupling and pulmonary vascular mechanics during acute exercise in 12 middle-aged men with a long-standing history of endurance training. Subjects underwent simultaneous right-heart catheterization and echocardiography, with measures obtained at steady state heart rates of 100, 130 and 150 beats/min. Subjects were highly trained and displayed RV remodeling of endurance-trained athletes. During exercise at 100 beats/min, systolic, diastolic, and mean pulmonary artery pressure increased significantly from rest, as did pulmonary capillary wedge pressure. The slope of pooled mean pulmonary pressure indexed to cardiac output was 1.436 mmHg⋅min-1⋅L-1 with a distensibility index of 0.112 ± 0.048 mmHg-1. The pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees) decreased from rest to exercise at 130 beats/min (P < 0.01). These results suggest that Ea:Ees becomes favourable for RV function during exercise, indicative of a pulmonary vasculature that is highly distensible and well matched to RV output.

Determining how coordinated gene expression changes direct embryonic heart development is paramount to understanding the genetic causes and developmental origins of congenital cardiomyopathies. Towards this goal, I present an optimized protocol for mouse thiouracil tagging (TU-tagging), a novel transcriptomics methodology for defining dynamic and cell specific gene expression programs, and validate TU-tagging for cardiovascular research. I then apply related and additional high-resolution approaches to characterize how vascular endothelial growth factor (VEGF) signaling coordinates cell and gene expression dynamics underlying heart ventricle development. TU-tagging is a powerful approach to study dynamic gene expression programs of defined cell types while they are natively embedded within a complex organ. TU-tagging integrates genetic and chemical approaches to provide temporally controlled in vivo covalent labeling of cell type–specific RNA. Here, I describe two significant optimizations of the TU-tagging molecular biology and bioinformatics workflows that improve the method’s ability to identify differentially expressed genes and expand the technology’s utility. Next, using chemical inhibition of VEGF signaling in combination with high-resolution imaging and transcriptomic methods, I show that VEGF signaling directly promotes formation of the trabeculae that uniquely develop in the heart ventricle. By RNA-Seq, I identify VEGF-dependent target genes, including Gpr126 and Bmp10, which encode additional signaling proteins. I further show that myocardial Bmp10 expression and resulting endocardial Bmp10-driven pSMAD1/5/8 signaling is under sustained control by endocardial VEGF signaling. This continuous VEGF-BMP signaling interplay between endocardial and myocardial cells led me to examine the dynamic tissue arrangements between the two cell types during early stages of trabeculation. By extensive staining and high resolution imaging, I show that endocardial cells can be subdivided into three classes; 1) quiescent cavity cells that are well-separated from the myocardium, 2) proliferative and signal responsive transition zone/stalk cells that directly interact with myocardium to coordinate both cell types’ activities, and 3) CD34-expressing migratory tip-like cells uniquely found at the base of forming trabeculae. VEGF promotes trabeculation by 1) driving proliferation of endocardial transition zone/stalk cells and, secondarily, neighboring myocardium, and 2) directing the outward migration of endocardial tip cells that causes myocardial tissue to accumulate within individual and extensive ridge-like trabeculae. Defining these multiple roles of VEGF signaling during ventricle development reveals a novel conceptual framework for understanding trabeculation mechanisms and therefore processes likely to be disrupted in common congenital cardiomyopathies. This dissertation includes previously published and unpublished co-authored material. / 10000-01-01

A seminal study by Morganroth et al (1975) demonstrated a differential pattern of cardiac adaptation with prolonged exercise training; of eccentric pattern of left ventricular hypertrophy (LVH) in endurance trained athletes (ET) and concentric LVH in resistance trained athletes (RT). Specific inconsistencies related to the nature of any adaptation to RT; the value of new imaging technologies; the relative importance of scaling of cardiac data for differences in body size; the impact of training on the right ventricle (RV) and the fit of differential pattern of adaptation in athletes with Black ethnicity have driven the rationale for the studies included in this thesis. Study one employed meta-analysis techniques to critically evaluate the evidence base supporting or refuting that MH exists in elite male Caucasian ET & RT. Modern echocardiographic techniques were used to test whether a dichotomous LV and RV structural as well as global and regional functional adaptation was apparent in elite Caucasian ET & RT in studies 2 & 3. The final study (exploratory) was to characterize the athletic heart phenotype in a homogenous population of elite RT of West African origin (WRT) to provide new insight in relation to cardiac adaptation and ECG characteristics in non-Caucasian athlete groups. Allometric scaling approach was deployed to index LV and RV data for individual body variance in body size. The novel findings of this thesis; larger LV data in ET (LVMg: ET 232 (200 to 260), RT 220 (205 to 234), CT 166 (145 to 186)) but no concentric hypertrophy in RT within the meta-analysis, predominance of normal geometry in male athletes (65% of ET and 95% of RT) and the lack of concentric pattern of hypertrophy in RT in a cross-sectional study; no RV adaptation in RT athletes (RVD1mm: ET 45 ± 5 (39 to 57), RT 40 ± 5 (32 to 51) CT 39 ± 4 (31 to 45)); no LV or RV adaptation in WRT athletes; the importance of appropriate scaling of cardiac parameters; provide a useful re-evaluation of concepts and models in the athletic heart literature. The findings have important implications for cardiovascular screening of athletes.

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Agradecemos a compreensão. on 2018-05-22T11:07:47Z (GMT) / Submitted by Michelli Fenerich (michellifenerich@hotmail.com) on 2018-05-23T00:06:49Z No. of bitstreams: 1 Dissertação Michelli Fenerich.pdf: 839583 bytes, checksum: 4eb04bc52d571c22b951ce3b11e0a705 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-05-23T16:47:59Z (GMT) No. of bitstreams: 1 fenerich_m_me_jabo.pdf: 839583 bytes, checksum: 4eb04bc52d571c22b951ce3b11e0a705 (MD5) / Made available in DSpace on 2018-05-23T16:47:59Z (GMT). No. of bitstreams: 1 fenerich_m_me_jabo.pdf: 839583 bytes, checksum: 4eb04bc52d571c22b951ce3b11e0a705 (MD5) Previous issue date: 2018-04-12 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma doença de origem genética, muito prevalente em cães da raça Boxer. Histologicamente ocorre atrofia dos cardiomiócitos do ventrículo direito (VD) e consequente infiltração fibroadiposa, levando ao aparecimento de arritmias ventriculares. Mesmo sendo as alterações miocárdicas microscópicas em sua maioria, estudos recentes têm identificado disfunção contrátil do ventrículo direito, mesmo em estágios iniciais da doença em humanos, tanto por técnicas convencionais de ecocardiografia quanto por técnicas mais avançadas, como no caso do speckle tracking. Por isso, o objetivo deste estudo foi avaliar se há disfunção miocárdica de VD detectável pela ecocardiografia convencional e pela técnica de speckle tracking bidimensional em cães da raça Boxer portadores da CAVD. Para tanto, utilizou-se cães da raça Boxer com idade superior a quatro anos, distribuídos em dois grupos de acordo com o resultado da avaliação Holter (GC: < 50 EVs/24h, n=11 e GD: > 100 EVs/24h, n=11). Os animais foram submetidos a ecocardiografia e avaliou-se diâmetro e comprimento interno do VD em sístole e diástole, encurtamento fracional da área do VD (FAC), excursão sistólica do plano anular da tricúspide (TAPSE), velocidade miocárdica sistólica do ânulo lateral da tricúspide derivada do Doppler tecidual (S’) e deformação (strain) e taxa de deformação (strain rate) longitudinal global da parede livre do VD, derivados da análise por speckle tracking. As variáveis foram comparadas entre os grupos pelo teste t de Student e de Mann-Whitney e a correlação entre variáveis ecocardiográficas convencionais e de speckle tracking e o número e severidade das arritmias pelo teste de correlação de Pearson, com nível de significância de 5%. Os grupos não foram estatisticamente diferentes e não houve correlação entre os dados. Os resultados da pesquisa demonstraram que a ecocardiografia, tanto na avaliação do VD por índices sistólicos convencionais quanto por aqueles derivados da técnica de speckle tracking não foram capazes de detectar disfunção miocárdica do VD em Boxers portadores de CAVD. / Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease with a high prevalence in Boxer dogs. Histologically, right ventricle (RV) cardiomyocytes’ atrophy occurs, and thus fibrofatty infiltration, triggering ventricular arrhythmias. Although the myocardial changes are mostly microscopic, recent studies in human beings have identified right ventricular systolic dysfunction even in the early stages of ARVC, both by conventional echocardiographic techniques and advanced methods, such as speckle tracking. Therefore, the aim of this study was to investigate if RV myocardial dysfunction is present in Boxers affected by ARVC, evaluated by conventional echocardiography and bidimensional speckle tracking technique. For this purpose, Boxers older than four years were recruited, and based on 24-hour Holter recording were divided in groups: GC:< 50 VPC/24h (n=11), or GD: > 100 VPC/24h (n=11). The following echocardiographic parameters were analyzed: RV internal dimension during systole and diastole; RV fractional area change (FAC); tricuspid annular plane systolic excursion (TAPSE); myocardial systolic velocity of lateral tricuspid annulus (S’), and global longitudinal strain and strain rate. Groups were compared by Student’ t-test or Mann-Whitney test according distribution, and correlation between conventional and speckle tracking echocardiographic variables, as well as number and severity of the ventricular arrhythmias were accomplished by the Pearson test, assuming a level of significance at 5%. Groups were considered similar, and there was no correlation among the evaluated parameters. Our findings suggesting that the echocardiographic evaluation of RV, either by conventional and speckle tracking techniques, were not able to detect systolic myocardial dysfunction in Boxers affected by ARVC. / FAPESP: 16/14800-7

O maior nicho neurogênico no encéfalo adulto está ao redor dos ventrículos laterais, mas a identificação das células que iniciam tal formação é controversa. Há uma inervação do peptídeo CART que pode abrir perspectivas para o entendimento de seu papel na modulação da neurogênese. Propormos estudar a citoarquitetura ultra-estrutural das células proliferativas na região periventricular e descrever a organização dessa região e sua inervação por axonios imunorreativos ao CART. Utilizamos ratos e camundongos adultos, preparados para análise ultraestrutural e neuroquímica em microscópios eletrônicos de transmissão e varredura de alta-resolução, de luz e laser confocal. O estudo da proliferação e inervação ocorreu com a administração do marcador de fase S BrdU e anticorpos anti-BrdU, anti-CART, anti-DCX, anti-GFAP e anti-GFP. Cada tipo celular do nicho neurogênico apresentou uma densidade própria de ir-BrdU. Identificamos células de revestimento ventricular inervadas por axônios. A maior densidade de inervação ir-CART ocorre ao longo do trajeto dos neurônios em formação. / The major neurogenic niche in adult brains surrounds the lateral ventricles, but the identity of the cell that initiates this process in controversial. There is an innervation made by the CART peptide that may lead to perspectives for understanding its role in modulation of neurogenesis. We propose to study the ultrastructural cytoarchitecture of proliferative cells in this region and its innervation by CART immunoreactive axons. We used adult rats and mice, prepared for ultrastructural and neurochemical analysis by transmission and high-resolution scanning electron, light and laser confocal microscopes. The proliferation and innervation studies occured with the S-phase marker BrdU and anti-Brdu, anti-CART, anti-DCX, anti-GFAP, anti-GFP antibodies. Each sort of cells in neurogenic niche presented a proper density of BrdU staining. We identified the cells lining the ventricle being innervated by axons. The major density of CART innervation occurs along the pathway of neurons in maturation process.