L’inflammation: Une réponse adaptative du système immunitaire face à une insulte est aujourd’hui reconnue comme une composante essentielle à presque toutes les maladies infectieuses ou autres stimuli néfastes, tels les dommages tissulaires incluant l’infarctus du myocarde et l’insuffisance cardiaque. Dans le contexte des maladies cardiovasculaires, l’inflammation se caractérise principalement par une activation à long terme du système immunitaire, menant à une faible, mais chronique sécrétion de peptides modulateurs, appelés cytokines pro-inflammatoires. En effet, la littérature a montré à plusieurs reprises que les patients souffrant d’arythmies et de défaillance cardiaque présentent des taux élevés de cytokines pro-inflammatoires tels le facteur de nécrose tissulaire alpha (TNFα), l’interleukine 1β (IL-1β) et l’interleukine 6. De plus, ces patients souffrent souvent d’une baisse de la capacité contractile du myocarde. Le but de notre étude était donc de déterminer si un lien de cause à effet existe entre ces phénomènes et plus spécifiquement si le TNFα, l’IL-1β et l’IL-6 peuvent affecter les propriétés électriques et contractiles du cœur en modulant le courant Ca2+ de type L (ICaL) un courant ionique qui joue un rôle primordial au niveau de la phase plateau du potentiel d’action ainsi qu’au niveau du couplage excitation-contraction. Les possibles méchansimes par lesquels ces cytokines exercent leurs effets seront aussi explorés. Pour ce faire, des cardiomyocytes ventriculaires de souris nouveau-nées ont été mis en culture et traités 24 heures avec des concentrations pathophysiologiques (30 pg/mL) de TNFα, IL-1β ou IL-6. Des enregistrements de ICaL réalisés par la technique du patch-clamp en configuration cellule entière ont été obtenus par la suite et les résultats montrent que le TNFα n’affecte pas ICaL, même à des concentrations plus élevées (1 ng/mL). En revanche, l’IL-1β réduisait de près de 40% la densité d’ICaL. Afin d’examiner si le TNFα et l’IL-1β pouvaient avoir un effet synergique, les cardiomyocytes ont été traité avec un combinaison des deux cytokines. Toutefois aucun effet synergique sur ICaL n’a été constaté. En outre, l’IL-6 réduisait ICaL significativement, cependant la réduction de 20% était moindre que celle induite par IL-1β. Afin d’élucider les mécanismes sous-jacents à la réduction de ICaL après un traitement avec IL-1β, l’expression d’ARNm de CaV1.2, sous-unité α codante pour ICaL, a été mesurée par qPCR et les résultats obtenus montrent aucun changement du niveau d’expression. Plusieurs études ont montré que l’inflammation et le stress oxydatif vont de pair. En effet, l’imagerie confocale nous a permis de constater une augmentation accrue du stress oxydatif induit par IL-1β et malgré un traitement aux antioxydants, la diminution de ICaL n’a pas été prévenue. Cette étude montre qu’IL-1β et IL-6 réduisent ICaL de façon importante et ce indépendamment d’une régulation transcriptionelle ou du stress oxydatif. De nouvelles données préliminaires suggèrent que ICaL serait réduit suite à l’activation des protéines kinase C mais des études additionelles seront nécessaires afin d’étudier cette avenue. Nos résultats pourraient contribuer à expliquer les troubles du rythme et de contractilité observés chez les patients souffrant de défaillance cardiaque. / Cytokines are immune system modulators that are secreted in response to an insult. Even though on the short term they play a crucial role in the healing process, the prolonged secretion of pro-inflammatory cytokines, locally or systemically, has many deleterious effects. For almost 20 years reports of alteration in serum cytokine levels have been emerging in patients with various heart failure aetiologies, however it is only recently that the role of inflammation in heart pathologies is being more and more studied. Indeed, several studies have shown that patients suffering from heart failure or arrhythmias have high levels of cytokines. Three particularly of these cytokines in particular are highly present and together they play a central role in the inflammatory response. Tumour Necrosis Factor alpha (TNFα), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) are secreted chronically by immune cells or the cardiomyocytes themselves and can possibly, as shown by animal studies, induce cardiac remodelling, hypertrophy, apoptosis, fibrosis and generation of highly reactive oxidative species (ROS) among other effects. Furthermore, accumulating evidence suggests that these pro-inflammatory cytokines are not only important mediators of cardiac remodelling that can contribute to worsening of heart failure but they have also been linked to cardiac arrhythmias and prolongation of action potential. Overall, the findings suggests a strong role for pro-inflammatory cytokines in affecting cardiac function and inducing electrical remodelling, thus we hypothesised that high levels of pro-inflammatory cytokines can affect the electrical and subsequently the contractile properties of the heart. Thus, the aim of this project was to help establish the effects of the above mentioned cytokines on the electrical and contractile properties of cardiac myocytes while exploring the mechanisms by which these cytokines mediate their effect. Using cultured intact mouse neonatal ventricular cardiomyocytes which were treated chronically with various cytokines, at a pathophysiological concentration (30 pg/mL), the specific objective of this study was to measure the direct effect of chronic cytokine treatment on the L-type calcium current (ICaL), an important ionic current responsible for the plateau phase of the action potential and in the excitation contraction coupling (ECC) and the current l and subsequently, determine via which pathways cytokines are able to affect the calcium current. Patch-clamp experiments in the whole-cell voltage-clamp configuration were used to measure L-type calcium current and showed that ICaL was not affected by TNFα. Furthermore, no effect at a significantly higher concentration of TNFα (1 ng/mL) could be observed. In contrast, chronic treatment of cardiomyocytes with IL-1β depressed ICaL by up to 40 %. Furthermore, when combining TNFα with IL-1β, two cytokines often reported to act synergistically, no further reduction in ICaL current density compared to IL-1β treatment alone was observed, showing the specificity of IL-1β response. Expression studies using qPCR to quantify the mRNA of CaV1.2, the underlying alpha subunit channel which encodes for ICaL, were conducted in order to determine if the reduction in current is due to a cytokine mediated change in gene expression. We found that none of the cytokines significantly affected levels of CaV1.2 mRNA. A key component of the inflammatory response is the induction of oxidative stress. Indeed, when challenged with cytokines cardiomyocytes exhibited significant increases in ROS level. In an attempt to reverse the depression of ICaL in response to IL-1β, we treated myocytes concurrently with antioxidants and IL-1β. While we observed a significant decrease in intracellular ROS levels, antioxidant therapy failed to restore current density, indicating thus, that ROS produced in response to cytokines does not regulate ion channels. New preliminary data suggests a role for members of the protein kinase C family in regulating the properties of CaV1.2 in response to cytokines. Nonetheless, exploring this avenue will require substantial experimentation and will be the subject of future work. Overall our experiments will help provide a better understanding of the role of cytokines in regulating the electric and contractile properties of cardiomyocytes in the setting of inflammatory cardiomyopathies.

Bakgrund: Hjärtsjukdom är den vanligaste dödsorsaken i västvärlden. De senaste åren har forskare upptäckt kopplingar mellan D-vitaminbrist och en ökad risk att insjukna i hjärt-och kärlsjukdom. Ny forskning tyder på att D-vitamin är oerhört viktigt del i immunförsvaret och för vår hälsa på många olika områden. Idag pågår ett stort antal studier som undersöker om D-vitaminbrist kan vara en riskfaktor för att drabbas av olika sjukdomar såsom ökad infektionskänslighet, cancer, depression, diabetes samt hjärt- och kärlsjukomar etc. Den rekommenderade dosen D-vitamin har varit omdiskuterad de senaste åren och myndigheter höjer rekommendationerna i takt med nya upptäcker inom forskningen. Syfte: Att undersöka om D-vitamintillskott kan användas som en kortsiktig behandling mot hjärtsvikt orsakad av hypertoni eller kardiohypertrofi. Metod: Detta examensarbete är en litteraturstudie där vetenskapliga artiklar har sökts via databasen PubMed med sökorden: “Vitamin D”,“heart failure”,”heart disease”. Av de artiklar som kunde erhållas så inkluderades sökresultaten till observationsstudier och kliniska studier. I de kliniska studierna varierade doserna mellan 100-400 g/dag. Slutligen valdes 6st studier ut och granskades noggrant. Dessa studier är sammanfattade i Tabell VI & Tabell VII. Resultat: Det kliniska randomiserade studierna visade att D-vitamin hade en statistisk signifikant reducerande effekt på det systoliska blodtrycket, parathormon (PTH), aldosteron koncentrationen, Brain natriuretic peptide (BNP) och C-reaktivt protein (CRP). Observationsstudierna visade att D-vitaminbrist kan leda till hypertoni, hjärt -och kärlrelaterade sjukdomar och kardiohypertrofi. Enligt observationsstudierna är D-vitaminbrist en oberoende markör för ökad mortalitet. D-vitaminbrist visade sig även kunna leda till en längre sjukhusvistelse hos både HF patienter och övrig population. De upptäckte även att HF patienter i regel har lägre D-vitamin koncentration än övrig population.   Diskussion: De kliniska randomiserade studierna har många brister i sin studiedesign. Det är inte tillräckligt stora med enbart 23-100st deltagare. Alla deltagare hade ej en uttalad D-vitaminbrist från studiens början, effekt av behandling blir därför svår att utreda. Observationsstudierna har sina redan kända brister och det är svårt att utreda ett orsakssamband. Det har gjorts för få studier för att säkert kunna besvara frågan om D-vitamins koppling till uppkomst av hjärt- och kärlsjukdom. Ännu fler, större, längre och noggrannare studier behövs. D-vitamins verkningsmekanism i kroppen behöver också utredas vidare. Studierna visade på en viss koppling mellan D-vitaminbrist och risken att drabbas av hjärt-och kärlsjukdom. Även om vissa samband kan observeras så har denna eventuella effekt idag ännu inte kunnat bekräftas i kliniska studier. Då vetenskapliga bevis fortfarande saknas kan D-vitamintillskott ännu inte rekommenderas som behandling mot hjärt-och kärlsjukdom. / Background: Heart disease is the leading cause of death among people in the northern countries. It is also very common with vitamin D deficiency. The geographical position affects the availability of UVB radiation and people avoid sunlight because of the risk of getting malign melanoma and other types of skin cancer. New research have shown that vitamin D is very important for us and vitamin D deficiency may play a role in many diseases such as depression, infection, autoimmune and cardiovascular diseases. This particular subject is still unexplored and more research have to be done to investigate vitamin D role in these diseases. The Vitamin D recommended dose have been questioned for many years and the agencies have been raising the recommended dose and is still investigating the subject. Objective: The aim of this study is to investigate if vitamin D supplements may decrease the risk of heart failure (HF). Methods: This bachelor thesis is a literature review. Article search is made in the database PubMed in February 2017 by using the keywords “vitamin D/heart disease/heart failure”. Inclusion criteria were clinical, controlled, randomized trials on human and observation studies, written in English.  Results: Six studies were chosen for this bachelor thesis, three of the studies are clinical randomized and three of the studies are observation studies. The doses given in the clinical studies varies between 100-400 g/daily. The clinical studies did find some statistic significant reduced effect comparing baseline with after treatment with vitamin D in the systolic blood pressure, aldosterone, PTH, EF%, CRP and BNP. The observation studies did find a correlation between vitamin D deficiency and a decreased risk getting hypertension and cardio hypertrophy. They also observed that vitamin D deficiency was common in HF patients. The observation studies also found that vitamin D deficiency is an independent predictor of increased mortality in patients with HF.     Conclusion: In the clinical studies the population was small and the time for the treatment was highly limited only 4 or 6 months. The treatment dose of Vitamin D was not a standard dose because it varied between the studies which made it hard to compare the results. The observation studies have its known limitations. It is hard to tell if patients with HF have vitamin D deficiency because they spend more time inside than healthy people. May the sickness cause some reaction in the body that leading to vitamin D deficiency or does vitamin D deficiency cause HF. Because lack of good quality in these six studies they have failed to show convincing results and correlation between vitamin D deficiency and HF. It is necessary with larger controlled, study over long time, randomized trials to investigate whether vitamin D deficiency can cause heart failure. More research has to be done.

Orientador: Marlos Gonçalves Sousa / Resumo: A doença valvar mitral tem alta prevalência em todo o mundo e é a enfermidade cardiovascular mais diagnosticada em cães. A referida enfermidade cardíaca possui caráter progressivo, que frequentemente leva à insuficiência cardíaca congestiva. Por sua vez, a insuficiência cardíaca congestiva é uma síndrome clínica complexa que leva a um baixo débito cardíaco, hipotensão e hipoperfusão tecidual, fazendo com que as demandas de diversos órgãos não sejam devidamente supridas. Com o intuito de ajustar a falha do coração como bomba, o organismo ativa uma série de mecanismos compensatórios que, em curto prazo, normalizam a pressão arterial. Dentre esses mecanismos, se destaca como um dos mais importantes, ativação do sistema nervoso autônomo simpático. Todavia, a ativação desses mecanismos, em logo prazo, resulta em progressão da disfunção ventricular, morte dos cardiomiócitos, desenvolvimento de sinais clínicos e óbito. Quando o débito cardíaco é prejudicado pela falha da função ventricular, a hipotensão relativa estimula os barorreceptores a ativar o sistema nervoso autônomo simpático, conduzindo ao aumento da concentração sérica de noradrenalina na insuficiência cardíaca congestiva. A noradrenalina é uma catecolamina endógena sintetizada pelas células cromafins na medula adrenal, que age em receptoresα1-adrenérgicos, promovendo o aumento da resistência vascular sistêmica, e em receptores β1-adrenérgicos, exercendo atividade inotrópica e cronotrópica positivas. No tratamento da insu... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Mitral valve disease has a high prevalence worldwide and is the most diagnosed cardiovascular disease in dogs. The referred cardiac disease presents a progressive character, which often leads to congestive heart failure. In turn, congestive heart failure is a complex clinical syndrome that leads to low cardiac output, hypotension and tissue hypoperfusion, causing the demands of various organs not to be adequately met. In order to adjust heart failure as a pump, the body activates a series of compensatory mechanisms that, in the short term, normalize blood pressure. Among these mechanisms, it stands out as one of the most important, sympathetic autonomic nervous system activation. However, the activation of these mechanisms, in the long term, results in progression of ventricular dysfunction, death of cardiomyocytes, development of clinical signs and death. The main mechanism is the activation of sympathetic autonomic nervous system. When cardiac output is impaired by failure of ventricular function, relative hypotension stimulates baroreceptors to activate the sympathetic autonomic nervous system, leading to increased serum noradrenaline concentration in congestive heart failure. Noradrenaline is an endogenous catecholamine synthesized by chromaffin cells in the adrenal medulla, which acts at α1 -adrenergic receptors, promoting the increase of systemic vascular resistance, and at β1 -adrenergic receptors, exerting positive inotropic and chronotropic activity. In the treatment... (Complete abstract click electronic access below) / Mestre

No description available.

No description available.

Os efeitos da utilização da terapia de ressincronização cardíaca (TRC) em pacientes com cardiopatia chagásica (CCC) são pouco conhecidos. O objetivo desse trabalho foi comparar o efeito dessa terapia em pacientes com CCC e não-chagásica. Foram estudados, retrospectivamente, todos os pacientes submetidos à ressincronização cardíaca, associados ou não ao cardioversor-desfibrilador implantável (CDI) no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo no período de julho de 2007 a dezembro de 2017. Para comparar a mesma variável em dois momentos diferentes foi utilizado Teste de Wilcoxon. Para a comparação de proporções foi utilizado o teste exato de Fisher. A análise de sobrevida foi feita utilizando-se o método de Kaplan-Meier com o \"Long rank test\" para comparar a sobrevida entre os grupos. Para a análise das variáveis associadas à mortalidade pós-implante utilizou-se a análise de regressão de Cox. Noventa e oito pacientes foram incluídos e divididos em três grupos de cardiopatia: chagásica (CCC) com 42 pacientes (42,9%); isquêmicos (ISQ) com 13 (13,3%) e nãoisquêmico não-chagásico (NINC) com 43 (43,9%). Os pacientes que receberam implante de TRC foram 71,4% e TRC associado ao CDI foram 28,5%. Não havia diferença estatisticamente significativa entre os grupos na avaliação das características clínicas, exceto pela predominância de pacientes do gênero masculino no grupo ISQ. Em relação aos bloqueios de condução intraventriculares, havia menor quantidade de bloqueio de ramo esquerdo (BRE) espontâneo e maior quantidade de BRE induzido no grupo CCC. As demais características eletrocardiográficas e ecocardiográficas eram semelhantes entre os grupos. A sobrevida de pacientes que recebem a TRC foi baixa após 48 meses de implante, independentemente do tipo de miocardiopatia e a despeito da melhora significativa da classe funcional e estreitamento do QRS dos pacientes. Todavia, a sobrevida em pacientes chagásicos foi significativamente menor quando comparada as demais miocardiopatias. Ademais, a melhora da fração de ejeção do ventrículo esquerdo (FEVE) e a redução do diâmetro diastólico final do ventrículo esquerdo (DDFVE) ocorreram significativamente apenas no grupo NINC. O aumento da idade, FEVEreduzida, presença de atraso da condução intraventricular não especificada (ACINE) e de bloqueio de ramo direito (BRD) e baixa classe funcional estão associadas a maior risco de morte após implante. As taxas de complicações cirúrgicas foram baixas em todos os grupos. A taxa de óbito cirúrgico é compatível com a gravidade desses pacientes. Conclui-se que a CCC apresenta resposta clínica à TRC, mas a mortalidade após 48 meses é maior que em outras cardiopatias. / The effects of using cardiac resynchronization therapy (CRT) in patients with Chagas\' heart disease (CCC) are poorly understood. The objective of this study was to compare the effect of this therapy in patients with CCC and non-Chagas\' disease. We retrospectively studied all patients submitted to cardiac resynchronization associated or not with the implantable cardioverter defibrillator (ICD) at the Clinical Hospital of Ribeirão Preto Medical School at the São Paulo University from July 2007 to December 2017. We use Wilcoxon\'s test to compare the same variable in two different times. Fisher\'s exact test was used to compare proportions. Survival analysis was done using the Kaplan-Meier method with the Long rank test to compare survival between groups. Cox regression analysis was used to analyze the variables associated with post-implantation mortality. Ninety-eight patients were included and divided into three groups: cardiopathy: chagasic (CCC) with 42 patients (42.9%); ischemic (ISQ) with 13 patients (13.3%) and non-ischemic non-chagasic (NINC) with 43 (43.9%). The patients who received CRT implantation were 71.4% and CRI associated CRT were 28.5%. There was no statistically significant difference between the groups in the assessment of clinical characteristics, except for the predominance of male patients in the ISQ group. In relation to intraventricular conduction blockades, there was a lower amount of spontaneous left bundle branch block (LBBB) and greater amount of LBBB induced in the CCC group. The other electrocardiographic and echocardiographic characteristics were similar between groups. The survival of patients receiving CRT was low after 48 months of implantation, regardless of the type of cardiomyopathy and despite significant improvement in functional class and QRS narrowing of patients. However, survival in chagasic patients was significantly lower when compared to other cardiomyopathies. In addition, the improvement of left ventricular ejection fraction (LVEF) and the reduction of the left ventricular end-diastolic dimension (LVEDF) occurred significantly only in the NINC group. Increased age, reduced LVEF, presence of unspecified intraventricular conduction delay and left bundle branch block, and low functional class are associated with a higher risk of death after implantation. Therates of surgical complications were low in all groups. The surgical death rate is compatible with the severity of these patients. It is concluded that CCC presents a clinical response to CRT, but mortality after 48 months is higher than in the other cardiopathies.

INTRODUÇÃO: A terapia de ressincronização cardíaca (TRC) é procedimento já incorporado às diretrizes do tratamento da insuficiência cardíaca crônica grave. Os efeitos sobre a repolarização ventricular são controversos e seu comportamento ainda precisa ser melhor definido por meios não invasivos. OBJETIVO: Analisar o comportamento da repolarização ventricular, através do mapeamento eletrocardiográfico de superfície (MES), em pacientes sob TRC. MÉTODOS: Foram estudados 52 pacientes sob TRC com indicação classe I das Diretrizes Brasileiras de Dispositivos Cardíacos Eletrônicos Implantáveis-2007, com idade média 58,8±12,3 anos, 31 homens, FEVE:27,5±9,2 e QRS:181,5±24,2ms. Foram excluídos os que não eram classe I e também os que usavam amiodarona, portadores de fibrilação atrial, marcapasso ou CDI prévios. O MES de 87 derivações (59 no tórax anterior e 28 no dorso) foi realizado em ritmo sinusal (BASAL) e sob efeito do ressincronizador (BIV) Através de medidas semiautomáticas foram obtidos o intervalo QT, QTc médio e a dispersão de QT (DQT) global das 87 derivações, nos dois modos de estimulação, em cada paciente. As mesmas medidas foram realizadas e comparadas nas três regiões discriminadas pelo MES (VD, Septo e VE). Caracterizamos assim, o comportamento global e regional do QT e sua dispersão na TRC. Utilizamos os testes t Student pareado e ANOVA para comparações múltiplas. Nível de significância de p< 0,05. RESULTADOS: O comportamento global do QTmédio foi sensivelmente menor em BIV que no BASAL (424,4±38,7 x 455,8±46,5ms; p<0,001), assim como o QTc médio (460,7±42,3 x 483,8±41,4ms; p<0,05) e a DQT (61,2±26,2 x 74,9±28,7ms; p<0,05). O QTmédio foi semelhante nas 3 regiões nos modos BASAL e BIV (p=ns), porém o QTc médio nas regiõess VD e VE mostrou-se significantemente menor no modo BASAL. Sob BIV, essa diferença foi notavelmente menor na região do VD. A DQT, em região do VE, por sua vez, foi significantemente menor em relação ao Septo, nos dois modos (BASAL: 40,5±23,1 x 55,7±28,7ms, p<0,01 e BIV: 30,6±20,4 x 47,1±20,2ms, p<0,001). A variação de efeito (D%) da TRC determinou redução do QTmédio nas 3 regiões (VD: p=0,0014; Septo: p=0,0001 e VE: p=0,0018), enquanto a DQT reduziu-se em VD: p=0,04 e VE: p=0,023. Em região septal, a redução da DQT não atingiu significância, embora tenha mostrado a mesma tendência de resposta. CONCLUSÃO: O Mapeamento Eletrocardiográfico de Superfície detectou redução global e regional dos valores da repolarização ventricular, através da análise do QTm, QTcm e DQT, por efeito da terapia de ressincronização cardíaca em pacientes com insuficiência cardíaca grave e BRE / BACKGROUND: Cardiac resynchronization therapy (CRT) is an already established procedure, which became part of the guidelines for severe chronic heart failure treatment. Its effects upon the ventricular repolarization are controversial, therefore CRT response still remains to be better defined by noninvasive methods. OBJECTIVE: The aim of this study was to analyze the ventricular repolarization response by body surface potential mapping (BSPM) in patients undergoing CRT. METHODS: Fifty-two patients undergoing CRT, mean age 58.8±12.3 years, 31 male, LVEF 27.5±9.2 and QRS duration 181.5±14.2ms, with indication class I of the 2007Guidelines for Implantable Electronic Cardiac Devices of the Brazilian Society of Cardiology, were studied. Those who were not in class I and/or in use of amiodarone, with atrial fibrillation, or with previous pacemaker or ICD, were excluded. Eighty-seven-lead BSPM examination (59 leads on the anterior chest and 28 on the back) was performed in sinus rhythm (BASELINE), and in biventricular pacing (BIV) with the resynchronization device on. Global values of QT and mean QTc intervals, and QT dispersion (DQT) were semiautomatically measured in all patients in the two pacing modes. Same measurements were made and compared in the three regions (RV, Septum and LV) discriminated by BSPM maps. Thus we characterized the global and regional QT response and its dispersion under CRT. t-Student paired test and ANOVA were used for multiple comparisons. Significance level: p<.05. RESULTS: The global mean QT response was considerably smaller in BIV pacing than in BASELINE (424.4±38.7 x 455.8±46.5ms; p<.001), and so were the mean QTc (460.7±42.3 x 483.8±41.4ms; p<.05) and DQT (61.2±26.2 x 74.9±28.7ms; p<.05). Mean QT was similar across the three regions in both pacing modes (p=ns); however, mean QTc in RV and LV regions was found to be significantly smaller in BASELINE. In BIV pacing such difference was considerably smaller in the RV region. On the other hand, DQT value in the LV region was significantly smaller compared to the Septum region in both modes (BASELINE 40.5±23.1 x 55.7±28.7ms. p<.01; and BIV 30.6±20.4 x 47.1±20.2ms. p<.001). Variation of CRT effect (D%) determined reduction of mean QT in the three regions, RV (p=.0014); Septum (p=.0001); and LV (p=.0018), while DQT was reduced in RV (p=.04) and LV (p=.023) regions. DQT reduction in the septal region was not significant, although it showed the same trend of response. CONCLUSION: body surface potential mapping detected reduction of global and regional ventricular repolarization values by analyzing QTm, QTcm and DQT variables under the effect of cardiac resynchronization therapy, in patients with severe heart failure and LBBB

Nos últimos anos, vários estudos têm demonstrado que durante o desenvolvimento da insuficiência cardíaca (IC) ocorre uma ativação no sistema imunológico, notadamente através de alterações nos níveis plasmático de citocinas pro e antiinflamatórias. Desta forma, estratégias terapêuticas têm sido utilizadas com o intuito de modular a ação destas citocinas e neste caso, o treinamento físico aeróbio parece promissor. Em nosso estudo, avaliamos o efeito de oito semanas de um programa de treinamento aeróbio em esteira para ratos com IC secundária a infarto do miocárdio (IM). Apesar da produção e expressão dos genes (TNF-<font face=\"symbol\">a, IL-6 e IL10) estarem aumentados nos músculo sóleo dos animais com IC, o programa de treinamento aeróbio foi capaz de reverter este quadro, demonstrando valores próximos aos animais normais (sem IC). Desta forma, nos estudo sugere que o treinamento aeróbio moderado demonstrou efeito antiinflamatório em animais com IC secundária a (IM), podendo exercer um importante papel como terapêutica em programas de reabilitação de doenças cardiovasculares. / Recently, several studies has demonstrated immune activation during heart failure (HF) development, notably through changes in plasmatic levels pro and anti-inflammatory cytokines. For this reason, therapeutic interventions have been used with targeting to modulate this cytokine action and in this way, endurance training may be promising. In our study, we evaluated the effect of 8 weeks of endurance training program in a treadmill for post-myocardial (MI) HF rats. Despite increased of levels and gene expression (TNF-<font face=\"symbol\">a, IL-6 e IL10) in soleus muscle of post-MI HF rats, endurance training was able to reverse this change, showing similar values that as founded in control group (without HF). In this way, our study suggests that moderate endurance training demonstrated anti-inflammatory effect in post-MI HF rats, and it may play an important role as therapeutic in rehabilitation programs of cardiovascular disease.

A Insuficiência Cardíaca (IC) é uma doença crônica e incapacitante de alta morbi-mortalidade que provoca mudanças na qualidade de vida relacionadas à saúde (QVRS). Foi realizado um estudo descritivo, correlacional tipo corte transversal com 138 pacientes com IC em seguimento ambulatorial com os objetivos de avaliar: o estado geral de saúde por meio do Medical Outcomes Survey 36 - Item Short-Form (SF-36), o impacto da IC na vida diária utilizando o Minnesota Living with Heart Failure Questionnaire (MLHFQ) e analisar as relações entre essas duas variáveis e do estado de saúde percebido e do impacto da IC com variáveis sócio-demográficas e clínicas. Os dados foram coletados por entrevistas e, posteriormente, processados e analisados por meio de estatística descritiva, teste de correlação de Pearson, teste t e ANOVA para comparação entre os grupos e análise da consistência interna dos instrumentos usados (? de Cronbach). O nível de significância foi de 0,05. Como resultados constatamos que a maioria dos pacientes era do sexo masculino, com idade média de 56 anos, casados, baixa escolaridade e aposentados com renda média mensal individual de dois salários mínimos. Clinicamente, apresentaram IC secundária à miocardiopatia Dilatada Idiopática seguida da miocardiopatia Chagásica com classe funcional (CF-NYHA) II e III, grave disfunção sistólica, ou seja, menor valor da fração de ejeção do ventrículo esquerdo (FEVE) e com outras doenças associadas. Os instrumentos apresentaram, em sua maioria, consistência interna satisfatória (0,44 a 0,88 para o SF-36 e 0,78 a 0,93 para o total do MLHFQ e suas dimensões). A avaliação dos valores do SF-36 pode variar de zero a 100 com maiores valores indicando melhor estado de saúde percebido enquanto a avaliação dos valores do MLHFQ varia de zero a 105 com maiores valores indicando maior impacto da IC na vida diária dos pacientes. Os resultados foram apresentados em média e desvio-padrão. Os componentes mais comprometidos do SF-36 foram os Aspectos físicos (36,8+41,2) e Aspectos emocionais (47,6+43,9). O MLHFQ obteve valor de 35,8 (+24,9) para o total, 13,6 (+11,5) para dimensão física e 8,3 (+6,7) para a emocional. A correlação entre os instrumentos foi de forte magnitude e todas estatisticamente significantes. O impacto da IC na vida das mulheres (41,2+24,3) foi maior que os homens (32,2+24,9). A correlação entre o MLHFQ e idade e tempo de seguimento ambulatorial apresentou-se negativa e fraca, mas estatisticamente significante apenas para o tempo. As correlações do MLHFQ total e as variáveis clínicas foram estatisticamente significantes. O impacto da IC tende a aumentar com menor FEVE e maior CF-NYHA. O estado de saúde percebido e o impacto da IC na vida diária estavam moderadamente comprometidos. Quanto pior a percepção sobre o estado geral de saúde mais os pacientes com IC sentem o impacto dessa condição crônica de saúde sobre sua vida diária. Os pacientes com IC apresentaram comprometimento no seu estado de saúde percebido e sofreram com o impacto dessa doença em suas vidas diárias afetando a qualidade de vida. Mensurar a qualidade de vida relacionada à saúde permite a identificação de aspectos relevantes percebido pelos pacientes. A utilização dessas medidas, ou seja, o estado de saúde percebido e o impacto da IC na vida diária tornam-se uma ferramenta na identificação desses aspectos. Os resultados advindos dessas medidas poderão ser usados para subsidiar a assistência à saúde desses pacientes. / Heart Failure (HF) is a chronic and debilitating condition of high morbidity and mortality that provokes changes in the health related quality of life (HRQL). A descriptive, correlational study type transversal cut with 138 outpatients with HF was performed with the objectives of assessing the general health condition by Medical Outcomes Survey 36 - Item Short-Form (SF-36), the impact of HF in daily life using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and analyzing the relations between these two variables and the perceived health condition and the impact of HF with socio-demographic and clinical variables. The data were collected through interviews and, subsequently, processed and analyzed by descriptive statistics, test on Pearson\'s correlation, t-test and ANOVA for comparison among the groups and analyses of internal consistency of the used instruments (Cronbach\'s ). The level of significance was 0,05. It was found that the most patients were men, average age 56 years old, married, low rate of literacy and retired with two minimum wages as individual monthly minimum revenue. Clinically, they presented HF secondary to Idiopathic Dilated myocardiopathy followed by Chagas\' myocardiopathy with functional class (CF-NYHA) II and III, serious systolic dysfunction, in other words, decreased value of left ventricular ejection fraction (LVEF) and with other related diseases. The instruments presented, mostly, satisfactory internal consistency (0,44 to 0,88 for SF-36 and 0,78 to 0,93 for the total MLHFQ and its dimensions). The assessment of the values of SF-36 may vary from zero to 100 with increased values indicating better perceived health condition and the MLHFQ assessment varies from zero to 105 with increased values indicating greater impact on daily patient\'s life. The results were presented in means and standard deviation. The most impaired components of SF-36 were the physical (36,8+41,2) and emotional (47,6+43,9) aspects. The MLHFQ achieved the value 35,8 (+24,9) for the total; 13,6 (+11,5) for the physical dimension and 8,3 (+6,7) for the emotional dimension. The correlation among instruments had a strong importance and all were statistically significant. The impact of HF on women\'s lives (41,2+24,3) was more severe than on men\'s (32,2+24,9). The correlation among the MLHFQ, the age and time in an outpatient clinic was presented as negative and weak, but statistically significant only for the time. The total and clinical variables correlations of MLHFQ were statistically significant. The impact of HF tends to increase with decreased LVEF and increased CF-NYHA. The general perceived health condition and the impact of HF on daily life were reasonably impaired. The more the perception on the general health condition the more the patients with HF feel the impact of this chronic health condition on their daily life. It is more common in young women patients with decreased time in outpatient clinic and whose condition was more severe related to the systolic dysfunction and to the symptoms. These patients need greater attention from the health team during the outpatient clinical care, especially in the onset of the medical assistance.

INTRODUÇÃO: A hipertensão pulmonar (HP) é comorbidade frequente em pacientes com insuficiência cardíaca (IC) e está associada ao pior prognóstico no pós-transplante cardíaco (TC). O teste de reatividade pulmonar realizado no préoperatório de TC avalia a reversibilidade da HP aos vasodilatadores, uma vez que a HP reversível tem melhor prognóstico. O nitroprussiato de sódio (NPS) é o vasodilatador mais utilizado, porém é associado a elevados índices de hipotensão arterial sistêmica, disfunção ventricular do enxerto transplantado e elevadas taxas de desqualificação para o TC. O sildenafil (SIL) é um inibidor seletivo da fosfodiesterase tipo 5 e utilizado no tratamento da HP idiopática, sem promover efeitos sistêmicos negativos. Neste estudo, objetivou-se avaliar os efeitos hemodinâmicos agudos do SIL e NPS sobre a HP de candidatos ao TC e seus efeitos sobre o remodelamento cardíaco reverso, definido como redução dos diâmetros ventriculares e melhora da função cardíaca, por meio da análise ecocardiográfica, hemodinâmica e bioquímica. MÉTODOS: Os pacientes foram submetidos, simultaneamente, ao cateterismo cardíaco direito para medida das pressões pulmonares, ao ecocardiograma, à dosagem sanguínea de BNP e à gasometria venosa, prosseguindo no estudo caso preenchessem os critérios de inclusão previamente estabelecidos. Os pacientes selecionados foram randomizados a receber NPS (1 - 2 ?g/Kg/min) ou SIL (100mg, dose única, via oral) e, após o período de tempo predeterminado, procedeu-se à nova avaliação hemodinâmica, ecocardiográfica e bioquímica. RESULTADOS: NPS e SIL reduziram significativamente a pressão sistólica da artéria pulmonar (NPS: 64,7 vs. 57mmHg, p = 0,002; SIL: 61,07 vs. 50mmHg, p < 0,001), porém o grupo que recebeu NPS apresentou redução acentuada da média da pressão arterial sistêmica (85,2 vs. 69,8mmHg, p < 0,001). Do ponto de vista ecocardiográfico, ambas as medicações promoveram redução da área ventricular direita (NPS: 29,2 vs. 25,7mm, p = 0,003; SIL: 29,4 vs. 23,8mm, p < 0,001) e elevação da fração de ejeção ventricular esquerda (NPS: 23,5 vs. 24,8 %, p = 0,02; SIL: 23,8 vs. 26 %, p < 0,001). Por outro lado, o grupo que recebeu SIL, ao contrário do NPS, apresentou melhora no índice de saturação venosa de oxigênio, medido pela gasometria venosa (SIL: 49,2 vs. 58,9%, p < 0,001). Os vasodilatadores não interferiram de forma significativa nos níveis séricos de BNP. CONCLUSÃO: Sildenafil e nitroprussiato de sódio reduziram significativamente a hipertensão pulmonar de pacientes com IC avançada. Ambos estiveram associados ao remodelamento cardíaco reverso, com diminuição da área ventricular direita e melhora da função cardíaca, medidos por parâmetros hemodinâmicos, ecocardiográficos e bioquímicos. O NPS, ao contrário do SIL, esteve associado à significativa hipotensão arterial sistêmica e piora do índice de saturação venosa de oxigênio. / INTRODUCTION: Pulmonary hypertension (PH) is a common comorbidity in heart failure (HF) patients and is associated with poor post heart transplant (HT) prognosis. The pulmonary reactivity test performed pre-operatively to the HT evaluates the reversibility of the PH to the vasodilators, since a reversible PH has a better prognosis. Sodium nitroprusside (SNP) is the most widely used vasodilator, but is associated with higher rates of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and higher rejection rates of the HT. Sildenafil (SIL) is a selective phosphodiesterase type 5 inhibitor and is used in the treatment of idiopathic PH, without producing negative systemic effects. This study aimed to evaluate the acute hemodynamic effects of SIL and SNP on the PH of HT candidates and their effects on reverse cardiac remodeling, defined as a reduction in ventricular diameter and improvement of cardiac function, through echocardiographic, hemodynamic and biochemical analysis. METHODS: The patients simultaneously underwent: right cardiac catheterization, to measure the pulmonary pressure, echocardiogram and blood dosage of BNP and venous gas analysis, continuing in the study if the previously established inclusion criteria were met. The selected patients were randomly given SNP (1 - 2 ?g/Kg/min) or SIL (100mg, single dose, orally) and after a predetermined period of time went for a new hemodynamic, echocardiographic and biochemical evaluation. RESULTS: SNP and SIL significantly reduced the systolic pulmonary artery pressure (SNP: 64.7 vs. 57mmHg, p = 0.002; SIL 61.07 vs. 50mmHg, p = 0.001). However the group which received SNP showed a marked reduction in mean systemic blood pressure (85.2 vs. 69.8mmHg, p < 0.001). From the point of view of the echocardiography, both the medications produced a reduction in right ventricular size (SNP: 29.2 vs. 25.7mm, p = 0.003; SIL 29.4 vs. 23.8mm, p < 0.001) and an increase of the left ventricular ejection fraction (NPS: 23.5 vs. 24.8 %, p = 0.02; SIL: 23.8 vs. 26 %, p < 0.001). On the other hand, the group which received SIL, unlike the SNP, showed improvements in the rate of oxygen venous saturation, measured by venous gas analysis (SIL: 49.2 vs. 58.9%, p < 0.001). Neither group significantly affected the serum levels of BNP. CONCLUSION: Sildenafil and sodium nitroprusside significantly reduced pulmonary hypertension in patients with advanced HF. Both were associated with reverse cardiac remodeling, with a reduction in right ventricular area and improvement of the cardiac function, measured by hemodynamic, echocardiographic and biochemical parameters. SNP, unlike SIL, was associated to significant systemic arterial hypotension and worsening of the rate of venous oxygen saturation.