Heart failure is a devastating disease which despite significant advances in therapy over the past two decades still results in a poor prognosis. Metabolic dysregulation is associated with heart failure; however, it remains unclear whether isoproterenol exerts deleterious effects through altered metabolic regulation. Whether metformin, a metabolic modulator, prevents isoproterenol-induced heart failure is unknown. The aim of this study was to determine whether metformin prevents functional and metabolic changes seen in the isoproterenol model of heart failure. Male Sprague-Dawley rats were administered isoproterenol and metformin for seven months. Thereafter, cardiac dimensions, metabolic gene expression and myocardial structural changes were assessed. Chronic administration of isoproterenol induced left ventricular dilatation and pump dysfunction and mitochondrial structural derangement. No changes were seen in metabolic gene expression. However, co-administration of metformin prevented isoproterenol-induced heart failure and retained mitochondrial structural arrangement. Therefore, cardiac dilatation and pump dysfunction induced by chronic administration of isoproterenol can be prevented by co-administering metformin.

Echocardiography has an prominent role in the era of CRT by virtue of its non-invasive nature with high feasibility and reproducibility. The clinical applications include not only quantification of the change in systolic function, hemodynamics, LV volume, or mitral regurgitation, but also assessment of systolic dyssynchrony. A number of new echocardiographic techniques were employed in this study, such as tissue Doppler imaging (TDI) and its post-processing modalities including strain, strain rate and displacement mappings, tissue synchronization imaging (TSI), as well as three-dimentional (3D) echocardiography. / For heart failure patients with wide QRS complexes who received CRT, LV volumes, cardiac function and synchronicity were shown to change acutely between CRT-on and CRT-off modes by both 2D and 3D echocardiography methods. Furthermore, the usefulness of 3D echocardiography and its accuracy in assessing volumetric changes / Systolic dyssynchrony, which illustrates discoordinated contraction of the heart, is relatively common in heart failure patients, in particular those with prolonged QRS complexes. It is caused by electromechanical delay in some regions of the failing heart and will result in further reduction of cardiac function. Cardiac resynchronization therapy (CRT) is a rapidly evolving pacing modality for advanced heart failure, characterized by implantation of the left ventricular (LV) lead through coronary sinus to the free wall region. It is recommended to patients who have refractory heart failure despite optimal medical treatment, LV dilatation with ejection fraction lower than 35%, and prolonged QRS duration on surface ECG. / The main findings were as followed: The Ts-SD was 17.0+/-7.8ms in normal control, 33.8+/-16.9ms in narrow QRS group and 42.0+/-16.5ms in wide QRS group, respectively. The prevalence of systolic dyssynchrony in heart failure population was 43% in the narrow QRS group, and 64% in the wide QRS group, when a Ts-SD of > 32.6 ms (+2 SD of normal controls) was used to define significant dyssynchrony. QRS duration does not have a linear relationship with systolic dyssynchrony. / TSI was useful to predict a reverse remodeling and gain in ejection fraction after CRT. Qualitative identification of the latest peak systolic contraction at the lateral wall was a quick and specific guide to predict a favorable reverse remodeling response while quantitative computation of "Asynchrony Index" from 12 LV segments in ejection phase was beneficial in the absence of lateral wall delay. In conclusion, the improvement of cardiac function and LV reverse remodeling after CRT is more obvious in heart failure patients with wide QRS complex and echocardiographic evidence of significant systolic dyssynchrony. Reverse remodeling is not only an objective measure of favorable responses, but also a prognosticator of disease outcomes. "Asynchrony Index" is a strong predictor of LV reverse remodeling response after CRT. Assessment of systolic dyssynchrony by various echocardiographic tools is promising, however, further studies are needed to compare the predictive values of different parameters objectively and prospectively. / We performed echocardiography with TDI in 200 subjects, including 67 patients with heart failure and narrow QRS complexes (≤ 120ms), 45 patients with heart failure and wide QRS complexes (>120ms), and 88 normal controls, which served as a polit study. Severity and prevalence of systolic dyssynchrony were assessed by the maximal difference in time to peak myocardial systolic velocity (Ts-dif-12) and the standard deviation (Ts-SD) of the 12 LV segments. / We recruited a group of seventy patients with chronic heart failure who fulfilled the established criteria and received CRT. Serial echocardiographic assessment with clinical evaluation was performed at baseline, predischarge, 1-month, 3-month, 6-month and long-term follow up. The objective was to demonstrate the improvement of cardiac function and dyssynchrony after CRT by echocardiographic parameters, in particular the reduction of LV end-systolic volume (LVESV) which is also known as reverse remodeling, and its relationship with the improvement in clinical status and prognosis. We also attempted to identify dyssynchrony parameters which are useful in predicting LV reverse remodeling after CRT. / Zhang Qing. / "October 2006." / Adviser: Yu Cheuk-Man. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5852. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Han, Jinghao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 182-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

INTRODUÇÃO: O benefício de um programa de treinamento físico em pacientes com insuficiência cardíaca tem sido bastante documentado. Contudo, pouco se conhece a respeito dos benefícios de um programa de treinamento fisco nãosupervisionado na qualidade de vida, capacidade física e no controle neurovascular, após uma fase inicial de treinamento físico supervisionado. Foi ainda objetivo deste estudo, analisar a efetividade de um programa de atividade física na redução dos níveis de catecolaminas plasmáticas, NT-ProBNP e Interleucina 6 em pacientes com disfunção ventricular na vigência de betabloqueadores. MÉTODOS: Trinta pacientes (idade 54±1,7 anos) com disfunção ventricular esquerda acentuada foram inicialmente selecionados para o estudo. Os pacientes foram divididos em 2 grupos: o grupo controle (n=12); e o grupo treinamento físico (n=18). No início do estudo todos tiveram a qualidade de vida avaliada pelo questionário de Minnesota, e foram dosados os níveis de Interleucina 6, NT-ProBNP, e catecolamina plasmática. A atividade nervosa simpática muscular foi registrada diretamente no nervo fibular através da técnica da microneurografia. O fluxo sangüíneo muscular em antebraço foi avaliado pela técnica da pletismografia de oclusão venosa. Ambos os procedimentos foram registrados em repouso e durante o exercício isométrico a 30% da contração voluntária máxima. A capacidade física foi avaliada por meio da ergoespirometria. O grupo treinamento foi submetido inicialmente a quatro meses de treinamento físico supervisionado composto por 3 sessões de 60 minutos por semana, mantendo uma freqüência cardíaca correspondente a 10% abaixo do ponto de descompensação respiratória determinado pela ergoespirometria. Após a fase de treinamento físico supervisionado, os pacientes foram orientados a realizar quatro meses adicionais de treinamento físico de forma não-supervisionada, na mesma freqüência e intensidade determinadas durante a fase de treinamento supervisionado. A medida da qualidade de vida, atividade nervosa simpática muscular, fluxo sangüíneo muscular e análise laboratorial foram repetidas em 4 meses em ambos os grupos e no oitavo mês apenas no grupo submetido ao treinamento físico. RESULTADOS: Após os quatro primeiros meses, o grupo treinado apresentou melhora na qualidade de vida comparado ao grupo controle (39±6 vs 42±5 pontos; p=0,014). A atividade nervosa simpática muscular em repouso e durante o exercício isométrico a 30% da contração voluntária máxima também apresentaram melhora (47±5 vs 73±6 impulsos/ 100 bat; p=0,0052) e (61±5 vs 77±6 impulsos/ 100 bat; p=0,034), respectivamente. O fluxo sangüíneo muscular em antebraço em repouso aumentou no grupo treinado (1,96±0,11 vs 1,51±0,12 ml/min/100 ml tecido; p=0,015). Quatro meses de treinamento físico não-supervisionado foram efetivos na manutenção dos benefícios na qualidade de vida (52±6 vs 36±6 vs 33±5 pontos; p=0,0001), no fluxo sangüíneo muscular em antebraço, tanto em repouso (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tecido; p=0,03) como durante o exercício isométrico (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tecido; p=0,0016) e na capacidade física (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). Não houve diferença nas medidas seriadas de NTProBNP, Interleucina 6 e de catecolaminas plasmáticas. CONCLUSÕES: O treinamento físico não-supervisionado por quatro meses, após uma fase de treinamento físico supervisionado, foi efetivo na manutenção dos benefícios na qualidade de vida, capacidade física e no fluxo sangüíneo muscular em antebraço. Não houve diferença nas medidas laboratoriais dos pacientes com disfunção ventricular esquerda treinados por oito meses / INTRODUCTION: The benefits of a physical training program in patients with heart dysfunction have been well described. However little is know about the response of a home-based exercise training in quality of life, physical capacity and neurovascular control in patients with heart failure, after a initial four months supervised training. The second objective of this study was to analyze the effectiveness of a exercise program on catecholamine, NT-ProBNP and Interleukin 6 in patients with heart dysfunction receiving beta-blockers. METHODS: Thirty patients (age 54±1,7 years) with severe heart dysfunction were initially enrolled in the protocol. They were divided in two groups; a control group (n=12) and a exercise group (n=18). Initially, both group had the measuring of quality of life by Minnesota questionnaire, Interleukin 6, NT-ProBNP and catecholamine. Muscle sympathetic nerve activity was recorded directly from fibular nerve using the technique of microneurography. Forearm blood flow was measured by venous plethysmography. Both procedures were recorded at rest and during 30% of maximal isometric contraction. The exercise group was submitted initially to fourmonths supervised exercise training program consisted of three 60 min exercise XXIX sessions per week, at heart rate levels that corresponded up to 10% below the respiratory compensation point. After the supervised period, the exercise group was instructed to perform an additional four-months home-based exercise training in the same frequency and intensity they had usually done. The quality of life, muscle sympathetic nerve activity, forearm blood flow and laboratory analysis were repeated at four months in both groups and only in the exercise group at eight months. RESULTS: After the initial 4 months the exercise group improved the quality of life compared to the control group (39±6 vs 42±5 units; p=0,014). The muscle sympathetic nerve activity at rest and during 30% of the maximum isometric contraction was also improved (47±5 vs 73±6 bursts/100 heart beat; p=0,0052) and (61±5 vs 77±6 bursts/100 heart beat; p=0,0276), respectively. The forearm blood flow at rest reduced in the exercise group (1,96±0,11 vs 1,51±0,11ml/min/100 ml tissue; p=0,015). An additional 4 month home-based exercise training was effective on the maintenance of the benefits on quality of life ( 52±6 vs 36±6 vs 33±5 points; p=0,0001), forearm blood flow at rest (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tissue; p=0,03), and during 30% of the maximum isometric contraction (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tissue; p=0,0016) and on physical capacity (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). There was no difference on the measurements of NT-ProBNP, Interleukin 6 and catecholamine. CONCLUSIONS: A home-based exercise training for four months, after a supervised phase, was effective on the maintenance of the benefits of quality of life, physical capacity and forearm blood flow. There was no difference on the laboratorial measurements after an eight months physical training on patients with heart dysfunction

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2018-01-11T13:15:59Z No. of bitstreams: 1 RANIERI CARVALHO CAMUZI.pdf: 15172783 bytes, checksum: 659642cc2290ea484c112a926143aed9 (MD5) / Made available in DSpace on 2018-01-11T13:15:59Z (GMT). No. of bitstreams: 1 RANIERI CARVALHO CAMUZI.pdf: 15172783 bytes, checksum: 659642cc2290ea484c112a926143aed9 (MD5) / Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro / A insuficiência cardíaca (IC) é uma síndrome prevalente que, apesar dos avanços no tratamento, acarreta significativa morbidade e mortalidade. Estudos demonstram que a não adesão ao tratamento é uma importante causa de resultados insatisfatórios na terapia, descompensação no quadro clínico, internação e óbito. Acreditando-se que a efetiva inserção do farmacêutico na assistência, mesmo na dispensação convencional, seria capaz de promover maior adesão, tevese por objetivo avaliar como dois modelos de atuação farmacêutica impactam sobre a adesão à farmacoterapia em pacientes com IC com fração de ejeção reduzida assistidos em dois centros clínicos especializados da rede pública de saúde. O trabalho foi organizado em duas partes. A primeira parte foi um estudo prospectivo com análise transversal de dados de pacientes com ICFER acompanhadas por uma equipe multidisciplinar, no momento da inserção do profissional farmacêutico nessa equipe e após 4 meses, com orientação farmacêutica por demanda do paciente. A segunda parte é a análise transversal de um estudo prospectivo que realizou acompanhamento farmacoterapêutico com pacientes de outro centro clínico especializado, por 4 meses. Foram incluídos respectivamente 38 e 31 pacientes. Nos dois grupos, observou-se maioria de homens, com predomínio de IC leve a moderada, polimedicados e tratando duas ou mais comorbidades, utilizando combinação de betabloqueador, inibidores da enzima conversora da angiotensina e/ou antagonistas dos receptores da angiotensina, antagonista da aldosterona e diurético. Na primeira parte do estudo, observou-se associação de maior número de comorbidades, maior gravidade e polifarmácia com boa adesão. Na segunda parte, verificou-se associação de idade maior, viver sem cônjuge e com menor número de pessoas no mesmo lar, razão de posse de medicamentos e razão para não tomar o medicamento com a adesão. Os resultados sobre adesão melhoraram nos dois grupos, ao final do estudo, embora sem significância estatística. Na segunda parte observou-se melhora estatisticamente significante no nível de conhecimento da prescrição, na razão de posse de medicamentos e na autoavaliação de saúde. Não foi possível observar melhora significativa na adesão, porém verificaram-se melhorias significativas em fatores associados à boa adesão. O limitado número amostral exigirá cautela na extrapolação dos resultados / Heart failure (HF) is a prevalent syndrome that, despite advances in treatment, causes significant morbidity and mortality. Studies show that nonadherence to treatment is an important cause of unsatisfactory results in therapy, decompensation in the clinical condition, hospitalization and death. Believing that the effective insertion of the pharmacist into the patient care would be able to promote greater adherence, even in the conventional dispensation, the objective of this study was to evaluate how two models of pharmaceutical services impact on adherence to pharmacotherapy in patients with HF with reduced ejection fraction, assisted in two specialized clinical centers of the public health network. The study was organized in two parts. The first was a prospective study with cross-sectional of data from patients assisted by a multidisciplinary team, at the time of insertion of the pharmacist in this team and after 4 months, with pharmaceutical orientation by patient demand. The second part is a cross-sectional analysis of a prospective study that carried out pharmacotherapeutic follow-up with patients from another specialized clinical center for 4 months. Thirty-eight and 31 patients were included respectively. In the two groups, was observed majority of men, with a predominance of mild to moderate HF, polymedicated and treating two or more comorbidities, using a combination of beta-blocker, angiotensin converting enzyme inhibitor and/or angiotensin receptor antagonist, aldosterone antagonist and diuretic. In the first part of the study, we observed an association of higher number of comorbidities, greater severity and polypharmacy with good adherence. In the second part, there was an association of older age, living with no spouse and with fewer people in the same household, reason for possession of medications and reason for not taking the drug with high adherence. The adherence level was improved in both groups at the end of the study, although without statistical significance. In the second part, there was a statistically significant improvement in the level of prescription knowledge, in the drug possession ratio and in the health self-assessment. It was not possible to observe a significant improvement in adherence, but there were significant improvements in factors associated with good adhesion. The limited sample size will require caution in extrapolating the results

INTRODUÇÃO: O benefício de um programa de treinamento físico em pacientes com insuficiência cardíaca tem sido bastante documentado. Contudo, pouco se conhece a respeito dos benefícios de um programa de treinamento fisco nãosupervisionado na qualidade de vida, capacidade física e no controle neurovascular, após uma fase inicial de treinamento físico supervisionado. Foi ainda objetivo deste estudo, analisar a efetividade de um programa de atividade física na redução dos níveis de catecolaminas plasmáticas, NT-ProBNP e Interleucina 6 em pacientes com disfunção ventricular na vigência de betabloqueadores. MÉTODOS: Trinta pacientes (idade 54±1,7 anos) com disfunção ventricular esquerda acentuada foram inicialmente selecionados para o estudo. Os pacientes foram divididos em 2 grupos: o grupo controle (n=12); e o grupo treinamento físico (n=18). No início do estudo todos tiveram a qualidade de vida avaliada pelo questionário de Minnesota, e foram dosados os níveis de Interleucina 6, NT-ProBNP, e catecolamina plasmática. A atividade nervosa simpática muscular foi registrada diretamente no nervo fibular através da técnica da microneurografia. O fluxo sangüíneo muscular em antebraço foi avaliado pela técnica da pletismografia de oclusão venosa. Ambos os procedimentos foram registrados em repouso e durante o exercício isométrico a 30% da contração voluntária máxima. A capacidade física foi avaliada por meio da ergoespirometria. O grupo treinamento foi submetido inicialmente a quatro meses de treinamento físico supervisionado composto por 3 sessões de 60 minutos por semana, mantendo uma freqüência cardíaca correspondente a 10% abaixo do ponto de descompensação respiratória determinado pela ergoespirometria. Após a fase de treinamento físico supervisionado, os pacientes foram orientados a realizar quatro meses adicionais de treinamento físico de forma não-supervisionada, na mesma freqüência e intensidade determinadas durante a fase de treinamento supervisionado. A medida da qualidade de vida, atividade nervosa simpática muscular, fluxo sangüíneo muscular e análise laboratorial foram repetidas em 4 meses em ambos os grupos e no oitavo mês apenas no grupo submetido ao treinamento físico. RESULTADOS: Após os quatro primeiros meses, o grupo treinado apresentou melhora na qualidade de vida comparado ao grupo controle (39±6 vs 42±5 pontos; p=0,014). A atividade nervosa simpática muscular em repouso e durante o exercício isométrico a 30% da contração voluntária máxima também apresentaram melhora (47±5 vs 73±6 impulsos/ 100 bat; p=0,0052) e (61±5 vs 77±6 impulsos/ 100 bat; p=0,034), respectivamente. O fluxo sangüíneo muscular em antebraço em repouso aumentou no grupo treinado (1,96±0,11 vs 1,51±0,12 ml/min/100 ml tecido; p=0,015). Quatro meses de treinamento físico não-supervisionado foram efetivos na manutenção dos benefícios na qualidade de vida (52±6 vs 36±6 vs 33±5 pontos; p=0,0001), no fluxo sangüíneo muscular em antebraço, tanto em repouso (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tecido; p=0,03) como durante o exercício isométrico (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tecido; p=0,0016) e na capacidade física (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). Não houve diferença nas medidas seriadas de NTProBNP, Interleucina 6 e de catecolaminas plasmáticas. CONCLUSÕES: O treinamento físico não-supervisionado por quatro meses, após uma fase de treinamento físico supervisionado, foi efetivo na manutenção dos benefícios na qualidade de vida, capacidade física e no fluxo sangüíneo muscular em antebraço. Não houve diferença nas medidas laboratoriais dos pacientes com disfunção ventricular esquerda treinados por oito meses / INTRODUCTION: The benefits of a physical training program in patients with heart dysfunction have been well described. However little is know about the response of a home-based exercise training in quality of life, physical capacity and neurovascular control in patients with heart failure, after a initial four months supervised training. The second objective of this study was to analyze the effectiveness of a exercise program on catecholamine, NT-ProBNP and Interleukin 6 in patients with heart dysfunction receiving beta-blockers. METHODS: Thirty patients (age 54±1,7 years) with severe heart dysfunction were initially enrolled in the protocol. They were divided in two groups; a control group (n=12) and a exercise group (n=18). Initially, both group had the measuring of quality of life by Minnesota questionnaire, Interleukin 6, NT-ProBNP and catecholamine. Muscle sympathetic nerve activity was recorded directly from fibular nerve using the technique of microneurography. Forearm blood flow was measured by venous plethysmography. Both procedures were recorded at rest and during 30% of maximal isometric contraction. The exercise group was submitted initially to fourmonths supervised exercise training program consisted of three 60 min exercise XXIX sessions per week, at heart rate levels that corresponded up to 10% below the respiratory compensation point. After the supervised period, the exercise group was instructed to perform an additional four-months home-based exercise training in the same frequency and intensity they had usually done. The quality of life, muscle sympathetic nerve activity, forearm blood flow and laboratory analysis were repeated at four months in both groups and only in the exercise group at eight months. RESULTS: After the initial 4 months the exercise group improved the quality of life compared to the control group (39±6 vs 42±5 units; p=0,014). The muscle sympathetic nerve activity at rest and during 30% of the maximum isometric contraction was also improved (47±5 vs 73±6 bursts/100 heart beat; p=0,0052) and (61±5 vs 77±6 bursts/100 heart beat; p=0,0276), respectively. The forearm blood flow at rest reduced in the exercise group (1,96±0,11 vs 1,51±0,11ml/min/100 ml tissue; p=0,015). An additional 4 month home-based exercise training was effective on the maintenance of the benefits on quality of life ( 52±6 vs 36±6 vs 33±5 points; p=0,0001), forearm blood flow at rest (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tissue; p=0,03), and during 30% of the maximum isometric contraction (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tissue; p=0,0016) and on physical capacity (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). There was no difference on the measurements of NT-ProBNP, Interleukin 6 and catecholamine. CONCLUSIONS: A home-based exercise training for four months, after a supervised phase, was effective on the maintenance of the benefits of quality of life, physical capacity and forearm blood flow. There was no difference on the laboratorial measurements after an eight months physical training on patients with heart dysfunction