Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease. Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II. Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation. Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

Submitted by Juliana Bornhausen Cardoso de Araujo null (jubsaraujo@gmail.com) on 2017-12-11T01:42:29Z No. of bitstreams: 1 defesa cest fini 10.12 c alteracoes v2.pdf: 1290180 bytes, checksum: eaea0777a91ea4b787d719a382f3dade (MD5) / Submitted by Juliana Bornhausen Cardoso de Araujo null (jubsaraujo@gmail.com) on 2017-12-11T18:47:11Z No. of bitstreams: 1 defesa cest fini 10.12 c alteracoes v2.pdf: 1290180 bytes, checksum: eaea0777a91ea4b787d719a382f3dade (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2017-12-12T12:42:54Z (GMT) No. of bitstreams: 1 araujo_jbc_me_bot.pdf: 1238650 bytes, checksum: 89edb88921e475bb18deb582a11ed4dd (MD5) / Made available in DSpace on 2017-12-12T12:42:55Z (GMT). No. of bitstreams: 1 araujo_jbc_me_bot.pdf: 1238650 bytes, checksum: 89edb88921e475bb18deb582a11ed4dd (MD5) Previous issue date: 2017-11-09 / A cinomose é uma relevante doença infectocontagiosa no Brasil e possui um crescente número de mortes em sua decorrência. É comprovado que esta doença causa importantes alterações histopatológicas cardíacas, porém seus efeitos sobre o sistema cardiovascular foram pouco descritos. O presente estudo teve como objetivo avaliar a atividade do vírus no coração por meio da ecocardiografia, da eletrocardiografia e da monitorização eletrocardiográfica ambulatorial, mais conhecida como método Holter. / Distemper is an important infectious disease in Brazil that unfortunately has a crescent death toll. It has been proven that the virus has important histopathologic effects over the cardiovascular system although that has been scarcely researched. The present study has the objective of evaluating the virus’s activity on the heart with the help of echocardiography, electrocardiography and Holter. The ambulatory electrocardiographic monitoring, also known as Holter exam, is an effective way of detecting cardiac arrhythmias and sometimes can help with early detection of cardiac lesions.

Orientador: Aparecido Antonio Camacho / Coorientador: Marlos Gonçalves Sousa / Banca: Wagner Luis Ferreira / Banca: Guilherme de Camargo Ferraz / Resumo: A doença mixomatosa da valva mitral (DMVM) é a enfermidade cardíaca mais frequente em cães. Embora as estratégias de tratamento mudem de acordo com o estágio da doença, programas de exercício não integram a terapia padrão da enfermidade. Em seres humanos já se demonstrou que o treinamento apropriado pode ser, inclusive, benéfico como adjuvante do tratamento de algumas enfermidades cardiovasculares. Nesse sentido, objetivou-se com este estudo avaliar os efeitos promovidos pelo condicionamento sistematizado em esteira em cães portadores de DMVM. Para tanto, 19 cães foram selecionados em quatro grupos conforme a severidade da enfermidade (fundamentada no tamanho da relação átrio esquerdo/aorta - Grupo A: controle; Grupo B: Ae/Ao<1,4; Grupo C: Ae/Ao1,4-1,8; e, Grupo D: Ae/Ao>1,8). O teste de esforço incremental foi realizado para detecção do limiar de lactato. Na sequência, foram realizadas oito semanas consecutivas de condicionamento, com base em 70% da velocidade do limiar de lactato. Os animais foram avaliados quanto à variabilidade da frequência cardíaca, além da dinâmica miocárdica, por meio de ecocardiografia convencional e tecidual. Foi empregado o teste de normalidade dos resíduos e análise de variância, seguida do teste de Tukey para comparação das médias dos diversos parâmetros estudados. As análises estatísticas foram realizadas com nível de significância de 5%. A análise estatística multivariada exploratória foi utilizada para a extração dos fatores, segundo critério de Kaiser. Os resultados de ecocardiografia demostraram aumento do diâmetro interno do ventrículo esquerdo em diástole, oito semanas após o condicionamento na comparação com avaliação inicial no grupo C, assim como, aumento do septo interventricular em sístole quatro semanas e oito semanas em relação ao valor basal no grupo A. Os valores da variabilidade da frequência cardíaca revelaram uma redução do desvio... / Abstract: The myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. Although treatment strategies change according to the stage of the disease, exercise programs are not part of the standard therapy of the disease. In human beings, it has been demonstrated that proper training can be beneficial as adjunctive treatment of certain cardiovascular diseases. This study evaluated the effects of systematic training on a treadmill in dogs with MMVD. Nineteen dogs were selected and divided into four groups according to the severity of illness (based on the size of the left atrium-to-aorta ratio - Group A: control; Group B: LA/Ao<1.4; Group C: LA/Ao 1.4 to 1.8, and Group D: LA/Ao>1.8). The incremental exercise test was performed to detect the lactate threshold. Eight consecutive weeks of training were performed based on 70% of the lactate threshold velocity. The animals were evaluated for the heart rate variability, as well as myocardial dynamics, by standard and tissue Doppler echocardiography. Test for residual normality, analysis of variance, and Tukey's test were all used to compare the means of several parameters. Statistical analyses were performed at a level of significance of 5%. Exploratory multivariate statistical analysis was used for the extraction of factors, according to the Kaiser criteria. The echocardiography results showed increased left ventricular internal diameter in diastole eight weeks after training as compared to the baseline value in group C, as well as an increased interventricular septum in systole at four weeks and eight weeks as compared to the baseline value in group A. Heart rate variability data revealed a reduction in standard deviation of all RR intervals (SDNN) in C and D groups in comparison with group A at baseline. Also, after two and four weeks of training significant differences were found to exist between all groups compared to group A. From standard deviations of the mean values of ... / Mestre

As dilatações vasculares intrapulmonares (DVIP) constituem a anormalidade vascular pulmonar mais freqüente e a principal causa de hipoxemia grave em hepatopatas. A associação de doença hepática, aumento do gradiente alvéoloarterial de oxigênio e DVIP é chamada de "síndrome hepatopulmonar". O objetivo principal deste estudo foi verificar se os níveis de DVIP aferidos por ecocardiografia com contraste estão relacionados à intensidade de shunt intrapulmonar, medida por dois diferentes métodos: cintilografia com 99mTc-MAA e gasometria com O2 a 100%. Foram estudados 28 candidatos a transplante hepático portadores com DVIP identificadas e graduadas por ecocardiografia conforme escala semi-quantitativa (graus I a IV). A idade média foi de 47,5 anos, e a doença hepática foi classificada como Child-Pugh B na maioria dos casos (60,7%). A intensidade das DVIP foi classificada como I, II, III e IV em 13 (46,4%), 9 (32,1%), 2 (7,1%) e 4 (14,3%) casos, respectivamente. Dos 28 pacientes, 21 (75%) tiveram quantificação de shunt pelo método cintigráfico e gasométrico, 6 (21,4%) apenas pelo método cintigráfico e 1 caso (3,6%) pelo método gasométrico apenas. A PaO2 média entre os pacientes com DVIP graus I e II por ecocardiografia foi 89,1 ± 11,0mmHg, enquanto naqueles com DVIP classificadas como graus III e IV foi 74,7 ± 13,2mmHg (p = 0,01). A média dos valores de shunt por cintilografia nos 27 pacientes submetidos ao exame foi 14,9 ± 9,0% do débito cardíaco (mínimo 6,9% e máximo 39%), sendo 11,7 ± 3,8% nos pacientes com DVIP graus I e II, e 26,3 ± 9,7% nos pacientes com DVIP graus III e IV (p = 0,01). A média dos valores de shunt pelo teste com O2a 100% foi 9,8 ± 3,9%, sendo 8,3 ± 2,3% nos pacientes com DVIP graus I e II, e 16,3 ± 2,6% nos pacientes com DVIP graus III e IV (p < 0,001). Observou-se uma relação estatisticamente significativa entre a graduação de DVIP por ecocardiografia e o valor de shunt aferido por gasometria com O2 a 100% (rs = 0,609, p < 0,01) e por cintilografia (rs = 0,567, p < 0,001). Observou-se relação estatisticamente significativa entre os valores de shunt medidos por cintilografia e aqueles medidos por gasometria com O2 a 100% nos 21 pacientes que se submeteram à quantificação de shunt pelos 2 métodos (rs = 0,666, p < 0,001). A avaliação semi-quantitativa do grau de DVIP por ecocardiografia apresentou correlação moderada a boa com os valores de shunt aferidos pelos dois outros métodos estudados, sendo que a melhor correlação foi observada com o teste com O2 a 100%. / Intrapulmonary vascular dilatations (IPVD) are the most common pulmonary vascular abnormality and the main cause of acute hypoxemia in patients with severe liver disease. The association of liver disease, increased alveolar-arterial oxygen gradient and IPVD is known as "hepatopulmonary syndrome". The chief aim of this study was to determine whether IPVD levels, as determined by contrast echocardiography, are related to intrapulmonary shunt intensity, as measured by Tc- 99m MAA scintigraphy and by 100% oxygen gasometry. Twenty-eight IPVD patients, all candidates for liver transplant, were studied. IPVD were identified using echocardiography and graded on the semiquantitative scale (levels I to IV). The mean age was 47.5 years. Liver disease was classified as Child-Pugh B in 60.7% of cases. IPVD intensity was classified as level I, II, III and IV in 13 (46.4%), 9 (32.1%), 2 (7.1%) and 4 (14.3%) cases, respectively. Of the 28 patients, shunt intensity was determined using both scintigraphy and gasometry in 21 patients (75%), by scintigraphy only in 6 (21.4%) and by gasometry only in 1 (21.4%). Mean PaO2 was 89.1 ± 11.0mmHg among level I and II patients and 74.7 ± 13.2mmHg among level III and IV patients (p = 0.01). The mean shunt by scintigraphy was 14.9 ± 9.0% of cardiac output (minimum 6.9% and maximum 39%), being 11.7 ± 3.8% among level I and II patients and 26.3 ± 9.7% among level III and IV patients (p = 0.01). The mean shunt by gasometry was 9.8 ± 3.9%, being 8.3 ± 2.3% among level I and II patients and 16.3 ± 2.6% among level III and IV patients (p < 0.001). There was a significative correlation between IPVD level and shunt intensity: rs = 0.609; p < 0.01 by gasometry and rs = 0.567; p < 0.001 by scintigraphy. In those patients undergoing both tests, a significant relation was found between shunt intensity as measured by scintigraphy and by gasometry: rs = 0.666; p < 0.001. Hypoxemic individuals had significantly higher levels of intrapulmonary vascular dilatation than did nonhypoxemic individuals. Semiquantitative evaluation of IPVD level showed moderate to good correlation with shunt intensity under each of the two methods used, with the better correlation being found under 100% oxygen gasometry.

Sub-endocardial fibres line the inner surface of both ventricles and are responsible for longitudinal oscillations of the mitral annulus, such oscillations may be measured using tissue Doppler echocardiography (IDE). During systole the annulus descends and during early diastole (ETDE) and atrial systole (ATDE) itascends. This thesis examined whether changes in the velocity of the annulus ineach of these phases of oscillation, measured using tissue Dopplerechocardiography (TDE), could determine the nature of increases in left ventricular size (pathological or physiological). Study one examined differences at rest in longitudinal velocities between individuals with hypertrophic cardiomyopathy (HCM), hypertension (HT), weightlifters, runners and controls, (n = 15 all groups) and all groups were aged between 20 - 36 years. The results demonstrated that both pathological groups had systolic and ETDE velocities significantly lower than groups with physiological hypertrophy (weightlifters or runners) or controls p < 0.05. AIDE however was not significantly different between groups. Additionally runners also demonstrated a significantly higher ETDE than either weightlifters or controls (p < 0.05). Binomial logistic regression identified longitudinal systolic velocity < 9 cm s" 1 and ETDE velocity < 11 cm s" 1 as the best combination of variables to predict pathological increases in heart size. Study two examined older subjects in order to determine whether the criteria set out in study one were applicable to senior athletes. The subject groups were the same as in study one however all subjects were aged between 36-55. In this case systolic annular velocity was significantly lower in groups with pathological LVH but ETDE < 9 cm s" 1 was a better differentiator. Binomial logistic regression identified ETDE < 9 cm s" 1 and a mitral E / A ratio < 1 as the best combination of variables to predict pathological LVH. Study three examined the age related changes in long axis function using the pooled data from studies one and two. This demonstrated that in the pathological LVH groups only ETDE / ATDE ratio was significantly correlated with age (r = - 0.5 p < 0.05) suggesting that there appears to be no summation of the effects of pathology and age on mitral annular velocities. The control groups demonstrated a significant age related reduction in all long axis variables (systolic velocity r = - 0.7 p < 0.05; ETDE r = - 0.6 p < 0.01; ATDE r = 0.5 p < 0.05; ETD E / ATDE r = - 0.5 p< 0.01). Weightlifters however did not demonstrate an age related decline in either systolic or diastolic annular velocities. Runners had no age related decline in systolic annular velocities, and whilst they had an age dependent fall in ETDE ( r = - 0.62 p < 0.05) the older runners ETDE were still significantly faster (p < 0.05) than that seen in control subjects. Study four investigated relationship between mitral annular velocity and VOiruK in runners, weightlifters and controls. These results demonstrated peak exercise E TDE strongly correlated to VO^PEAK (r = 0.8 p < 0.01). ConclusionsTaken together these data suggest that longitudinal velocities of the mitral annulus may be useful in determining the nature of increases in heart size, in addition the increased performance of endurance - trained athletes is due in part to functional changes of the long axis.

O objetivo desse estudo foi determinar se os índices de função, volume (VAE) e área (AAE) do átrio esquerdo (AE) podem ser utilizados para avaliar a gravidade da degeneração valvar crônica de mitral (DVCM) em cães, bem como diagnosticar a insuficiência cardíaca congestiva (ICC) nestes pacientes. A hipótese é que o aumento dos volumes e decréscimo da função atrial esquerda possa estar associado com a gravidade da DVCM e também com a ICC. Oitenta cães foram incluídos em um estudo clínico transversal observacional e prospectivo, sendo agrupados de acordo com a gravidade DVCM. Os cães foram igualmente distribuídos nos grupos A, B1, B2 e C + D, de acordo com o estadiamento para DVCM proposto pelo American College of Veterinary Internal Medicine. A mudança fracional da área (FAC) e a fração de ejeção atrial esquerda (FEAE) foram calculados com as seguintes equações: FAC total = 100 x (AAEmáxima AAEmínima) / AAEmáxima, FAC passiva = 100 x (AAEmáxima AAEpa) / AAEmáxima e FAC ativa = 100 x (AAEpa AAEminima) / AAEpa, cujas as mensurações foram realizadas no corte apical quatro câmaras; e FEAE Total = 100 x (VAEmáxima VAEmínima) / VAEmáxima, FEAE passiva = 100 x (VAEmáxima VAEpa) / VAEmáxima e FEAE ativa = 100 x (VAEpa VAEminima) / VAEpa, calculadas por meio do método biplanar área-comprimento, no corte apical quatro e duas câmaras. A FAC total, FAC ativa, FEAE total e FEAE ativa foram significativamente menores nos pacientes do grupo C+D do que as observadas nos demais grupos. Também foi observado que com o agravamento da DVCM ocorreu o aumento do VAEmáximo/kg, VAEpa/kg, VAEmínimo/kg, AAEmáximo/m2, AAEpa/m2, AAEmínimo/m2. Os volumes do AE, bem como suas áreas, apresentaram grande acurácia e aumentaram a capacidade para diagnosticar a ICC nos cães do DVCM. Conclui-se que a função atrial esquerda total e ativa é reduzida nos cães com ICC secundária a DVCM quando comparados aos cães saudáveis e naqueles com DVCM sem ICC. Além disso, os volumes e as áreas atriais podem ser utilizados para diagnosticar a ICC nesses pacientes / This study aimed to determine whether left atrial (LA) function indices, volume (LAV) and area (LAA) can be used to assess severity of mitral valve chronic degeneration (MVCD) in dogs, as well as to diagnose congestive heart failure (CHF) in these patients. The hypothesis stated that the increase in left atrial volumes and decrease in function are associated with the severity of MVCD and also with CHF. Eigthy dogs were included in a cross sectional prospective observational clinical study, grouped according to the severity of MVCD based on clinical signs and echocardiographic evaluation. Dogs were equitatively distribuited among groups A, B1, B2 and C + D, according to MVCD staging proposed by the American College of Veterinary Internal Medicine. The fractional area change (FAC) and left atrial ejection fraction (LAEF) were calculated based on the following equations: total FAC = 100 x (LAAmaximum LAAminimum) / LAAmaximum, passive FAC = 100 x (LAAmaximum LAApa) / LAAmaximum and active FAC ativa = 100 x (LAApa LAAminimum) / LAApa, which measurements were performed in four chamber apical view; and total LAEF = 100 x (LAVmaximum LAVminimum) / LAVmaximum, passive LAEF = 100 x (LAVmaximum LAVpa) / LAVmáximum and active LAEF = 100 x (LAVpa LAVminimum) / VLAVpa , calculated by biplanar arealength method in four and two-chambers apical view. The total and active FAC, total LAEF and active LAEF were significantly smaller in pacients from group C+D than the observed in the other groups. With increasing severity of MVCD there was increase in LAVmaximum/kg, LAVpa/kg, LAVminimum/kg, LAAmaximum/m2, LAApa/m2, LAAminimum/m2. LA volumes, as well as LA areas had a good performance as diagnostic methods, with high accuracy and increased capacity for heart failure detection in dogs with MVCD. In conclusion, left atrial total and active function are reduced in dogs with HF secondary to MVCD when compared with healthy dogs and dogs with MVCD without HF. Moreover, atrial volumes and areas can be used to diagnose HF in these patients

A insuficiência cardíaca é a doença crônica com maior impacto na sobrevida e qualidade de vida dos pacientes. Apesar do constante desenvolvimento de novas estratégias de tratamento, esta doença continua atingindo altos índices de mortalidade. O coração adulto tem capacidade de regeneração limitada e há grande evidência experimental de que os transplantes de células-tronco poderiam ser uma abordagem eficiente na recuperação do miocárdio lesado. Contudo, a maioria dos estudos são realizados em cardiomiopatias isquêmicas, existindo poucos estudos na cardiomiopatia dilatada (CMD). Em função disto, este trabalho foi realizado com o objetivo de avaliar a regeneração do miocárdio em coelhos com CMD induzida pela doxorrubicina, por meio do uso de células-tronco mesenquimais (MSC) obtidas de tecido adiposo, associadas ou não com plasma rico em plaquetas (PRP). Foram utilizadas 40 coelhas, Nova Zelândia, e um coelho macho doador das MSCs derivadas do tecido adiposo. As coelhas foram divididas em dois grupos: CMD induzida pela doxorrubicina e o grupo saudável. Cada grupo foi subdividido conforme o tratamento recebido: solução fisiológica, MCSs, PRP e MSCs associadas ao PRP. Os subgrupos receberam o tratamento por injeção diretamente no miocárdio no ventrículo esquerdo mediante toracoscopia vídeo assistida. Os coelhos foram avaliados por exames de ecocardiograma, eletrocardiograma, troponina I, no dia da chegada, após a indução da CMD e 15 dias após o recebimento das terapias. Nesta última avaliação, foi realizada a eutanásia e coletado o coração para análise histológica. Foi observado que após a indução, a troponina I se elevou, o segmento QRS visto no eletrocardiograma, aumentou e, no ecocardiograma, as frações de ejeção (FE) e encurtamento (FS) diminuíram e o diâmetro sistólico do ventrículo esquerdo (VEs) aumentou, em todos os animais avaliados. Após os tratamentos, o subgrupo MSCs obtiveram os melhores resultados em todas as análises citadas. Houve menor elevação da troponina I, o segmento QRS diminuiu, as FS e FE aumentaram e o VEs diminuiu. No exame histopatógico, analisado pela coloração de hematoxicilina-eosina, constatou-se que o subgrupo MSCs apresentou menos lesões, e nos subgrupos MSCs associadas com PRP, solução fisiológica e PRP as lesões aumentaram gradualmente, respectivamente. Os resultados sugerem que o uso das MSCs melhoraram a função cardíaca em coelhos com cardiomiopatia dilatada e que há necessidade de mais estudos no uso de PRP no miocárdio. / Heart failure is a chronic disease with major impact on survival and quality of patient’s life. Despite the constant development of new treatment strategies, this disease still affects high mortality rates. The adult heart has limited ability to regenerate and there is experimental evidence that large transplants of stem cells could be an effective approach in the recovery of injured myocardium. However, most studies are performed in ischemic cardiomyopathy, there are few studies in dilated cardiomyopathy. Because of this, this study aimed at evaluating the regeneration of the myocardium in rabbits with dilated cardiomyopathy induced by doxorubicin through the use of mesenchymal stem cell (MSC) derived from adipose tissue, associated or not with platelet-rich plasma (PRP). 40 New Zealand rabbits were utilized and a male rabbit donor MSCs derived from adipose tissue. The rabbits were divided into two groups: dilated cardiomyopathy doxorubicin-induced and the healthy group. Each group was divided according to treatment received: saline, MSCs, PRP and MSCs associated with PRP. The subgroups receiving treatment through an injection directly into the myocardium of the left ventricle through video-assisted thoracoscopy. The rabbits were evaluated by echocardiogram, electrocardiogram, troponin I, on the day of arrival, after induction of dilated cardiomyopathy and 15 days after receipt of therapies. This last evaluation, euthanasia was performed and the hearts collected for histological analysis. It was observed that after induction the troponin I increased, the QRS segment, seen on the electrocardiogram, increased, and, in echocardiography, the ejection and shortening fractions decreased, and left ventricular systolic diameter increased in all animals evaluated. After treatments, the subgroup MSCs have the best results in all tests cited. There was a lower elevation of troponin I, decreased QRS segment, the ejection and shortening fractions increased and left ventricular systolic diameter decreased. On examination histologic, analyzed by hematoxylin-eosin staining, the subgroup found that MSCs had fewer injuries, and in the subgroups MSCs associated with PRP, PRP and saline lesions gradually increased, respectively. The results suggest that the use of MSCs improved cardiac function in rabbits with dilated cardiomyopathy and that there is need for more studies on the use of PRP in the myocardium.

Made available in DSpace on 2015-07-22T20:50:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-30. Added 1 bitstream(s) on 2015-08-11T03:25:31Z : No. of bitstreams: 1 Publico-00388.pdf: 783398 bytes, checksum: 5ad5aa9fa9c1b1087f37cc5d3c15b281 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução e objetivos: as disfunções sistólica e diastólica do ventrículo direito, secundárias às lesões residuais após a correção cirúrgica da tetralogia de Fallot, contribuem para a morbidade e mortalidade no pós-operatório tardio. Embora estas lesões residuais possam ser avaliadas pela ecocardiografia Doppler, a relação entre os parâmetros ecocardiográficos e os níveis de proBNP (fragmento N-terminal do pró- BNP), um potencial biomarcador de sobrecarga ventricular direita, ainda não está bem estabelecida. Os objetivos do estudo foram analisar, em pacientes no pós-operatório de tetralogia de Fallot, a relação dos níveis plasmáticos de proBNP com parâmetros ecocardiográficos das dimensões das cavidades cardíacas direitas e da gravidade das lesões residuais, e os possíveis marcadores ecocardiográficos de níveis elevados de proBNP. Métodos: os níveis séricos de proBNP e os parâmetros ecocardiográficos foram obtidos no mesmo dia em 49 pacientes no pós-operatório tardio de tetralogia de Fallot (idade média de 14,7 anos, 51% do sexo feminino, com tempo médio de pós-operatório de 9,5 anos). Os parâmetros Doppler ecocardiográficos analisados foram: dimensões do átrio e ventrículo direitos, funções sistólica e diastólica ventricular direita e lesões pulmonares residuais. A relação entre estas variáveis e os níveis de proBNP foi analisada com testes de correlação de Pearson e análises uni e multivariada. Os valores de corte dos parâmetros ecocardiográficos preditores de níveis elevados de proBNP foram analisados pela curva ROC. Resultados: os níveis de proBNP estavam elevados em 53% dos pacientes e correlacionaram-se com o diâmetro diastólico do ventrículo direito (r= 0,41; p=0,003), com diâmetros longitudinal (r= 0,52; p=0,0001) e transversal (r= 0,47; p=0,001) do átrio direito, com o tempo de me0,41; p=0,005) e com o índice do refluxo pulmonar (r= -0,60; p<0,001). Pela análise multivariada o índice do refluxo pulmonar (R= -597; p=0,001; IC: -913,2 a -280,8) e o diâmetro longitudinal do átrio direito (R= 7,74, p<0,001; IC: 4,18 a 11,31) foram preditores independentes de proBNP elevado. Tempo de meia-pressão menor que 64 ms e índice do refluxo pulmonar menor que 0,65 apresentaram a melhor acurácia para indicar proBNP elevado. Conclusões: os níveis de proBNP podem estar elevados no pós-operatório tardio de tetralogia de Fallot e correlacionaram-se com as dimensões das câmaras direitas e com a gravidade do refluxo pulmonar. Valores de corte das dimensões das câmaras direitas e dos índices de gravidade do refluxo pulmonar podem se constituir em parâmetros úteis no seguimento dos pacientes no pós-operatório tardio de tetralogia de Fallot com lesão residual.ia-pressão da curva de velocidade do refluxo pulmonar (r= - / Background: Although the residual lesions after surgical correction of tetralogy of Fallot (TOF) can be evaluated by Doppler echocardiography (DE), the relation of DE parameters with the proBNP level, a potential biomarker of right ventricle overload, is not well known. The objective this study was to evaluate the DE parameters and their relation to proBNP levels. Methods: proBNP plasma level and Doppler echocardiography parameters were obtained in the same day in 49 patients later after repair of TOF (mean age of 14.7 years, 51% female, mean PO time of 9.5 years). The DE parameters studied were the dimensions of the right atrium (RA) and ventricle (RV), RV diastolic and systolic function and residual pulmonary lesions. The relation between them and proBNP levels were analyzed and the cutoff values of DE parameters for elevated proBNP determined. Results: proBNP was elevated in 53% and correlated with RV diastolic diameter (r=0.41; p=0.003), RA longitudinal (r=0.52; p=0.0001) and transversal (r=0.47; p=0.001) diameters, pressure half time of pulmonary regurgitation (PR) velocity (PHT) (r= -0.42; p=0.005) and the PR index (r=-0.60; p<0.001). By multivariate analysis the PR index (r=-597; p=0,001; CI: -913.2 to –280.8) and RA longitudinal (r=7.74; p<0,001; CI 4.18 to 11.31) were independent predictors of elevated proBNP. PHT lower than 64 ms (0.76) and PRi lower than 0.65 (0.81) had the best accuracy for elevated proBNP. Conclusion: proBNP may be increased in patients after surgical repair of TOF, correlated with the size of right cardiac chambers and the severity of PR. / TEDE / BV UNIFESP: Teses e dissertações

Master of Science / Department of Kinesiology / Carl Ade / Background: Androgen Deprivation Therapy (ADT) is a commonly used treatment for prostate cancer with controversy currently surrounding its association with long-term cardiovascular disease risk. Therefore, the aim of the current investigation was to non-invasively measure left ventricular mechanics at rest and during submaximal exercise in human prostate cancer survivors with and without a history of ADT. Methods: Eighteen prostate cancer survivors, 9 with a history of ADT and 9 matched (1:1) non-ADT controls, completed the protocol. Standard and tissue Doppler echocardiography were used to evaluate left ventricular systolic and diastolic function at rest and during submaximal cycling exercise. Results: At rest, there were no differences between groups. Ejection fraction was not different between groups at rest or during exercise (rest p=0.7; exercise p=0.8). During exercise, systolic left ventricular longitudinal strain and strain rate failed to increase in the ADT group (p=0.4; p=0.07), but significantly increased in the non-ADT group (p=0.03; p=0.02). During exercise, systolic strain was significantly different between groups (p=0.02). Diastolic longitudinal strain increased with exercise in both groups (p=0.003; p=0.003). In the ADT group during exercise, mitral valve deceleration time was not significantly different from rest (p=0.8) and was slower compared to non-ADT (p=0.03). Conclusion: In prostate cancer survivors with a history of ADT, there are significant abnormalities of left ventricular systolic function that become apparent with exercise. These findings may hold significant value beyond the standard resting characterization of ventricular function, in particular as part of a risk-stratification strategy.

Os polifenois são normalmente considerados compostos que apresentam atividades biológicas promissoras, em especial pelos seus efeitos antioxidantes e anti-inflamatórios. No entanto, estudos recentes têm demonstrado que o consumo materno de alimentos ricos em polifenois (ARP) durante a gestação interfere na dinâmica de fluxo do ductus arteriosus (DA) no coração fetal de humanos, provavelmente pelo efeito anti-inflamatório dos polifenois, e também tem sido demonstrado que a restrição da ingestão de ARP é capaz de reverter a constrição ductal. Neste trabalho, um estudo experimental foi desenvolvido com ovelhas prenhas, no qual os animais receberam suplementação oral de polifenois durante 14 dias. Realizou-se ecocardiografia fetal e a análise de amostras de sangue e urina para investigar biomarcadores de estresse oxidativo e inflamação além da excreção de polifenois totais na urina. Houve aumento nas velocidades sistólicas (VS) e diastólicas (VD) e uma diminuição no índice de pulsatilidade (IP), o que indica uma constrição prematura do DA após o consumo de polifenois. Houve diminuição da peroxidação lipídica, determinada pelos níveis de TBARS, e nos níveis de tióis reduzidos não proteicos após o tratamento. Houve um aumento das atividades das enzimas catalase (CAT) e glutationa peroxidase (GPx) após o tratamento. Apesar do não envolvimento de dano lipídico na constrição ductal, observou-se um aumento no dano proteico através da dosagem de proteínas carboniladas (PCO). O efeito vasoconstritor e anti-inflamatório foi verificado pela diminuição nos níveis de nitritos/nitratos (NOx) após o consumo de polifenois. O estresse oxidativo estava associado com parâmetros de constrição ductal, através das correlações de dano protéico (PCO) com VS (r=0,629, p=0,028), VD (r=0,905, p=0,0001) e IP (r=-0,772, p= 0,003). Ainda, VS foi correlacionada com catalase (r=0,672, p=0,033) assim como IP com GPx (r=-0,629, p= 0,05). A constrição ductal estava ainda associada com o parâmetro inflamatório, sendo VS e VD correlacionadas com NOx (r=-0,853, p=0,0004 e r=-0,705, p=0,010, respectivamente) além da correlação entre IP e NOx (r=0,599, p=0,039). Além disso, ambos os mecanismos anti-inflamatórios e antioxidantes estavam correlacionados: NOx e GPx (r=-0,755, p=0,004) e entre NOx e catalase (r=-0,812, p=0,001), confirmando a ocorrência de ambos efeitos atribuíveis aos 10 polifenois. Neste estudo, foi possível perceber que um elevado consumo de polifenois induziu constrição ductal em ovelhas prenhas com uma excreção urinária aumentada de polifenois totais e alterações em biomarcadores de estresse oxidativo e inflamação. Estes resultados ressaltam a necessidade de uma orientação dietética ao final da gestação com relação ao consumo de alimentos ricos em polifenois devido à possibilidade de indução de constrição ductal através da ação anti-inflamatória em fetos expostos. / Polyphenols are often referred to as compounds with promising biological activities, especially antioxidant and anti-inflammatory effects. However, it has been recently reported that maternal consumption of polyphenol-rich foods (PRF) interferes with ductus arteriosus (DA) flow in human fetuses’ hearts, probably by an anti-inflammatory effect and it has also been shown that restriction of PRF ingestion reverses ductal constriction. In this work, an experimental study was carried out with pregnant sheep, in which the animals received oral polyphenol supplementation for 14 days. Fetal echocardiography was performed along with blood and urine analysis to investigate antioxidant and anti-inflammatory biomarkers and total polyphenol (TP) urinary excretion. We found a decrease in lipid peroxidation by TBARS levels and a decrease in non-protein reduced thiols after treatment. In addition, an increase in enzymatic activities of catalase (CAT) and glutathione peroxidase (GPx) was observed. Despite that lipid peroxidation was not involved in ductal constriction, protein damage by enhanced protein carbonyls (PCO) were found. Anti-inflammatory and vasoconstrictive effects were observed by a decrease in nitrites/nitrates (NOx) in pregnant sheep after polyphenol consumption. Oxidative stress was associated to ductal constriction parameters, according to the correlations.of protein damage marker PCO to SV (r=0.629, p=0.028), VD (r=0.905, p=0.0001) and IP (r=-0.772, p=0.003). Also, SV was positively correlated to CAT (r=0.672, p=0.033) and IP negatively correlated to GPx (r=-0.629, p=0.05). Ductal constriction was also associated to the inflammatory parameter, due to the correlations of SV and DV to NOx (r=-0.853, p=0.0004 and r=-0.705, p=0.010, respectively) as well as the correlation between IP and NOx (r=0.599, p=0.039). Besides, association of both inflammatory and antioxidant mechanisms were found: NOx vs. GPx (r=-0.755, p=0.004) and NOx vs. CAT (r=-0.812, p=0.001), confirming the presence of both effects attributed to polyphenols. We report that high polyphenol intake induced fetal DA constriction in pregnant sheep followed by an increased TP excretion and alterations in inflammatory and oxidative biomarkers. These results highlight the need for a dietary orientation in late-pregnancy regarding maternal intake of foods with high polyphenol contents in light of the possible induction of ductal constriction through an anti-inflammatory action of polyphenols in exposed fetuses.