Background: Stem cell therapy can facilitate cardiac repair after healed myocardial infarction but the optimal cell type remains uncertain. Aims: To investigate the pathophysiology of heart failure in a canine model of healed myocardial infarction and to compare the efficacy and the safety of autologous bone marrow mononuclear cell (BMNC) transfer and mesenchymal stem cell (MSC) transfer in this model. It was a blind, randomized and placebo control study. Methods: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of BMNC, MSC or Placebo (n = 8 per groups). Echocardiography, conductance method, magnetic resonance imaging, serum neurohormones, holter monitoring, macromorphometry, histology and real time quantitative polymerase chain reaction were used to assess cardiac performance, safety and remodelling in healthy animals, before cell transplantation and up to 16 weeks’ follow-up. Results: The model was characterized by decreased left ventricular end-systolic elastance and ventricular-arterial uncoupling without alteration of compliance. Four months after BMNC transfer, the regional systolic function measured at echocardiographic showed a sustained improvement. This improvement was associated with an improved left ventricular end-systolic elastance and a decreased infarct size. Although the left ventricular ejection fraction stayed unchanged, the serum level of N-terminal B-type natriuretic propeptide level decreased. Mononuclear cell transfer was also associated with increased left ventricular relative wall area, increased vascular density, intramyocardial vascular remodelling and upregulation of angiogenic factors gene expression. Mesenchymal stem cell transfer only improved lately and moderately the regional systolic function, without improvement of cardiac contractility or decreased infarct size. Conclusions: In a canine model of chronic myocardial infarction, BMNC transfer is superior to MSC transfer in improvement of cardiac contractility and regional systolic function, and to reduce the infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favourable angiogenic environment and neovascularization.

INTRODUÇÃO: A doença de Chagas tem patogênese não totalmente conhecida. Ao contrário das funções sistólica e diastólica do ventrículo esquerdo, a função do átrio esquerdo carece de informações. OBJETIVOS: Em portadores de doença de Chagas, com ou sem alterações eletrocardiográficas, com ou sem disfunção sistólica de ventrículo esquerdo, verificar se há diferença nos parâmetros de função atrial esquerda e se há correlação entre dados de função de átrio esquerdo e parâmetros ecodopplercardiográficos de função ventricular sistólica e diastólica de ventrículo esquerdo MÉTODOS: 85 indivíduos: 10 controles (GC), 26 na forma indeterminada (GI), 30 com alterações eletrocardiográficas somente (GII) e 19 com disfunção ventricular (GIII), submetidos a ecocardiograma para avaliação da função atrial e das funções sistólicas e diastólicas ventriculares. Para analise estatística foi utilizado teste de Kruskal-Wallis e o coeficiente de Spearman. RESULTADOS: Função de reservatório (FET: fração de esvaziamento total): Houve diferença entre os grupos (p < 0,0001), média menor no GIII comparado ao GC (p = 0,003), ao GI (p < 0,001) e GII (p < 0,001), sem diferença entre GC, GI e GII. Fluxo de veias pulmonares: na onda S houve diferença entre os grupos (p = 0,003), média menor no GIII comparada ao GC (p = 0,01). Função de conduto (FEP: fração de esvaziamento passivo): houve diferença entre os grupos (p = 0,004), média menor no GIII, sem significância estatística comparando entre os grupos (GIII e GC, p = 0,06, GI e GII, p = 0,06, e GII e GIII, p = 0,07). Função de bomba propulsora (FEA: fração de esvaziamento ativo): houve diferença entre os grupos (p = 0,0001), média menor no GIII comparado ao GC (p = 0,05), ao GI (p < 0,0001) e ao GII (p = 0,002). Correlações: E/e\'média e FET: fraca correlação negativa (r = - 0,263; p = 0,02), moderada correlação negativa no GIII (r = - 0,58; p = 0,02). E/e\'média e FEP: não houve correlação (r = - 0,09; p = 0,44). E/e\'média e FEA: moderada correlação negativa (r = -0,36; p = 0,002) e no GIII (r = - 0,57; p = 0,04). e\'média e FET: moderada correlação positiva (r = 0,53; p < 0,0001). e\'média e FEP: moderada correlação positiva (r = 0,49; p < 0,0001). e\'média e FEA: moderada correlação positiva (r = 0,39; p = 0,001). Fração de ejeção do VE e FET: moderada correlação positiva (r = 0,35; p = 0,003) e no GIII (r = 0,52; p = 0,04). Fração de ejeção do VE e FEP: moderada correlação positiva (r = 0,42; p < 0,0001). Fração de ejeção do VE e FEA: moderada correlação positiva (r = 0,35; p = 0,003). CONCLUSÕES: Em pacientes com miocardiopatia chagásica com disfunção sistólica de ventrículo esquerdo, houve comprometimento das funções de reservatório, de conduto e bomba propulsora do átrio esquerdo e aqueles com função sistólica normal não apresentaram alterações nessas funções / BACKGROUND: Chagas disease (CD) pathogenesis is not fully known. Unlike the systolic and diastolic function of the left ventricle, the left atrial function still lacks information. OBJECTIVES: The aim of this study was to observe differences in patients with CD regarding the parameters of left atrial function and correlate them with Doppler echocardiographic parameters CASUISTIC AND METHODS: 85 subjects: 10 controls (GC), 26 in the indeterminate form (GI), 30 with ECG changes and normal left systolic function (GII) and 19 with left ventricular dysfunction (GIII) underwent echocardiography to assess left atrial and ventricular systolic and diastolic functions RESULTS: Reservoir function (TEF: total emptying fraction): there was a difference between groups (p <0.0001), lower mean in GIII compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001) with no difference between GC, GI and GII. Pulmonary veins flow: the S wave was no difference between groups (p = 0.003), lower mean in GIII compared to the CG (p = 0.01). Conduit function (PEF: passive emptying fraction): there was a difference between groups (p = 0.004), lower mean in GIII, without statistical significance between groups (GIII and GC, p = 0.06, GI and GII, p = 0.06, and GII and GIII, p = 0.07). Pump function (AEF: active emptying fraction): there was a difference between groups (p = 0.0001), lower mean in GIII compared to CG (p = 0.05), GI (p <0.0001) and GII (p = 0.002). Correlations: E/e\'mean and TEF: weak negative correlation (r = - 0.263, p = 0.02), moderate negative correlation in GIII (r = - 0.58, p = 0.02). E/e\'mean and PEF: no correlation (r = - 0.09, p = 0.44). E/e\'mean and AEF: moderate negative correlation (r = -0.36, p = 0.002) and GIII (r = - 0.57, p = 0.04). e\'mean and TEF: moderate positive correlation (r = 0.53, p <0.0001). e\'mean and PEF: moderate positive correlation (r = 0.49, p <0.0001). e\'mean and AEF: moderate positive correlation (r = 0.39, p = 0.001). LV ejection fraction and TEF: moderate positive correlation (r = 0.35, p = 0.003) and GIII (r = 0.52, p = 0.04). LV ejection fraction and PEF: moderate positive correlation (r = 0.42, p <0.0001). LV ejection fraction and AEF: moderate positive correlation (r = 0.35, p = 0.003). CONCLUSIONS: In patients with Chagas\' cardiomyopathy with left ventricular systolic dysfunction, there was impairment of the functions of reservoirs, conduit and pump of the left atrium

- 4 - Abstract Adaptation to hypoxia or exercise training has cardioprotective effects against acute ischemic injury, but can potentially negatively influence heart function. Possible negative changes depend on the degree of hypoxia and exercise training intensity. It is therefore necessary to evaluate the effects of the specific adaptation protocols used. The ideal technique is echocardiography, which enables non-invasive, repeated and long-term measurements of the same individual allowing to study the development of changes in the course of adaptation. The aim of this study was to determine the effects of selected protocols of adaptation to intermittent hypobaric hypoxia (corresponding to the altitude of 4,000 to 8,000 meters above sea level, for 15 weeks in total) and exercise training (running speed 30 m.min-1 for 60 min a day, 4 weeks in total) on the left ventricle geometry and systolic function in rats. We assessed basic echocardiographic parameters of the ventricle geometry and function such as fractional shortening, ejection fraction, stroke volume, cardiac output etc. The adaptation of rats to intermittent hypobaric hypoxia lead neither to the impairment of systolic function nor to the development of left ventricle hypertrophy compared to controls; signs of moderate hypertrophy were observed only...

<p>Background: Stem cell therapy can facilitate cardiac repair after healed myocardial infarction but the optimal cell type remains uncertain. <p>Aims: To investigate the pathophysiology of heart failure in a canine model of healed myocardial infarction and to compare the efficacy and the safety of autologous bone marrow mononuclear cell (BMNC) transfer and mesenchymal stem cell (MSC) transfer in this model. It was a blind, randomized and placebo control study.<p>Methods: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of BMNC, MSC or Placebo (n = 8 per groups). Echocardiography, conductance method, magnetic resonance imaging, serum neurohormones, holter monitoring, macromorphometry, histology and real time quantitative polymerase chain reaction were used to assess cardiac performance, safety and remodelling in healthy animals, before cell transplantation and up to 16 weeks’ follow-up. <p>Results: The model was characterized by decreased left ventricular end-systolic elastance and ventricular-arterial uncoupling without alteration of compliance. <p>Four months after BMNC transfer, the regional systolic function measured at echocardiographic showed a sustained improvement. This improvement was associated with an improved left ventricular end-systolic elastance and a decreased infarct size. Although the left ventricular ejection fraction stayed unchanged, the serum level of N-terminal B-type natriuretic propeptide level decreased. Mononuclear cell transfer was also associated with increased left ventricular relative wall area, increased vascular density, intramyocardial vascular remodelling and upregulation of angiogenic factors gene expression. Mesenchymal stem cell transfer only improved lately and moderately the regional systolic function, without improvement of cardiac contractility or decreased infarct size. <p>Conclusions: In a canine model of chronic myocardial infarction, BMNC transfer is superior to MSC transfer in improvement of cardiac contractility and regional systolic function, and to reduce the infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favourable angiogenic environment and neovascularization. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished