Left ventricular (LV) volume analysis in small animals has proven difficult because of the small size of the hearts and the rapid heart rate. Furthermore, there is a substantial contribution to the signal from both the blood as well as the muscle. Admittance - based measurement techniques has been proven effective in eliminating the muscular component and estimating the blood component accurately. The key factor that makes this measurement effective is the fact that the measurement is made in the complex plane, which measures both the magnitude as well as the phase of the complex phasor. This dissertation presents the design of a wireless telemetric device that measures impedance magnitude and phase measurements along with pressure from conscious, ambulatory rats. Using this impedance data along with other calibration data such as blood resistivity, stroke volume etc., volume is determined. / text

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Chronic lung diseases are often complicated with pulmonary hypertension (PH). This can lead to disability and poor prognosis. Oxidative stress has been implicated in the development of PH and right ventricular hypertrophy (RVH).A possible new way to treat lung disease related pulmonary hypertension is allopurinol (a xanthine oxidase inhibitor) which decreases both uric acid and oxidative stress. We hypothesised that allopurinol could regress RVH in patients with pulmonary hypertension associated with chronic lung disease (PH-CLD).In a double-blind, randomised controlled clinical trial, 72 patients with PH-CLD (93% diagnosed with chronic obstructive pulmonary disease and 17% with interstitial lung disease) were randomised to receive either allopurinol 300 mg twice daily or placebo for twelve months. The primary outcome was the mean change in right ventricular mass (RVM) as assessed by cardiac magnetic resonance imaging (CMRI) at twelve months. The secondary outcomes were the change in other cardiac parameters measured by CMRI, St George's Respiratory Questionnaire, Short Form 36, spirometry and six-minute walk test (6MWT).The mean age was 71 years, the mean FEV1 was 60% with mean resting SaO2 of 96%. After 12 months, there was no significant change in RVM. There were also no significant changes in other cardiac parameters measured on CMRI, quality of life questionnaires, spirometry and 6MWT. Post-hoc subgroup analysis showed that allopurinol reduced RVM (allopurinol -6.16 g vs placebo 0.75 g, p = 0.02) in COPD patients with more severe airflow limitation. Patients with higher NT-proBNP (> 489 pg/ml) had a greater improvement in left ventricular ejection fraction with allopurinol 5.12 vs placebo -1.62, p = 0.02.In summary, allopurinol had no overall impact but reduced RV mass in COPD patients with more severe airflow limitation. Further studies are warranted to assess the longer term impact of allopurinol in more severe COPD.

published_or_final_version / Community Medicine / Master / Master of Philosophy

No description available.

Left ventricular flows in the human heart are very complex and in the presence of a diseased condition, such as unhealthy or prosthetic heart valves, the complexity of the flow is further increased. The intricacy of the heart geometry combined with the pulsatile character of the flow, the interaction of high-speed jets with the flexible walls, and the unsteady motion of the heart valve leaflets generate inherently complicated flow fields. It is therefore essential that we study and understand the complex cardiac energetics and physics of blood flow in both healthy and diseased hearts. Although artificial heart valves, mechanical and biological, have evolved to a level of universal acceptance, they have never reached a level of performance comparable to that of the natural valves of the heart. Many of the problems are directly related to the fluid mechanics. Considering that mechanical heart valves (MHV) are more commonly implanted because of their durability, it is imperative to better understand their hemodynamic behavior. Yet to date, no study has documented in depth the complex hemodynamic characteristics of left ventricular flows and assessed the intricate structures that are generated in the left ventricle (LV) due to vortex formation (roll-up of shear layers shed past the valve leaflets), turbulence characteristics, and energetics. The flow through pivoted leaflets of MHVs induces a combination of flow characteristics that are dependent on the specific valve design and orientation. The aim of the present study is to provide new insight into the spatio-temporal dynamics of the flow distal to a mitral MHV by employing a state-of-the-art, high resolution, flow diagnostic method, Time Resolved Digital Particle Image Velocimetry (TRDPIV) in a flexible, transparent LV documenting the evolution of eddies and turbulence during a complete period of the heart cycle. The broad impact of the proposed research extends beyond the hemodynamics of heart valve prosthesis. The research herein will enable the development of a tool for application in all cardiac energetic studies (unhealthy valves, tissue engineered valves, cardiac remodeling stages, and even congestive heart failure) and aid in better diagnosis of the efficiency and performance of the heart. The last component of the dissertation involved the translation of my dissertation research into an engineering educational tool for undergraduate engineering students. / Ph. D.

Advances in the imaging techniques of the heart have fueled the interest in understanding of right heart pathology. Recently, speckle tracking echocardiography has shown to aid in understanding various right heart diseases and better management. Its role is well established in diagnosing right heart failure, pulmonary artery hypertension, arrhythmogenic right ventricular dysplasia and congenital heart disease. We review the basic mechanics of speckle tracking and analyze its role in various right heart conditions.

Few therapeutic alternatives exist for patients with a failing single ventricle physiology. To address this need, this thesis project investigated two new therapeutic alternatives, which sought to positively augment the Fontan hemodynamics. The first modality introduced a non-invasive method of external pressure application to the lower extremities. A clinical study (n=2) was conducted, and results indicated an increase in flow as a consequence to an increase in transmural pressure in the lower extremities. The second modality investigated a minimally invasive blood pump. Numerical analyses of the pump were performed to examine hydraulic performance under physiologic conditions. The pump produced pressure rises of 1 to 25 mmHg over flows of 1 to 4 LPM, has a blood damage index less than 1% and was also found to successfully augment the hydraulic energy of the Fontan physiology. This work resulted in substantial progress to develop both modalities and address a significant human health problem.

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.

Orientador: Aparecido Antonio Camacho / Resumo: 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... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: 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, assumin... (Complete abstract click electronic access below) / Mestre