Hjärtsvikt är en av Sveriges största folksjukdomar och en vanlig orsak till sjukhusvistelse. Kvalificerad professionell vård i hemmet kan minska antalet inneliggande vårddygn för den hjärtsviktssjuke. Lyfts inte hjärtsviktssjuka personers behov av stödjande insatser fram finns risk för att professionella vårdare i hemmet inte uppmärksammar den sjukes behov av psykosocialt stöd. Syftet med litteraturstudien var att beskriva behovet av psykosocialt stöd för den hjärtsviktssjuke personen som vårdas i hemmet. Systematisk litteraturstudie valdes där 19 artiklar analyserades genom kvalitativ innehållsanalys. Det framkom två huvudkategorier; professionella stödet och det informella stödet. Resultatet beskriver behovet av stödjande insatser i form av psykosocialt stöd den hjärtsviktssjuke erfar i hemmet. Då den professionella vården gjorde en helhetsbedömning av den hjärtsviktssjuke uppmärksammades psykosociala behov hos den sjuke. Genom att stärka den inneboende förmågan med stödjande insatser kunde den sjuke hantera de psykiska symtom som hjärtsvikt medförde. För det professionella stödet var delaktighet av största vikt, delaktighet ökade känslan av att bemästra sjukdomssituationen och stärkte värdigheten hos den sjuke. Litterturstudien riktar sig främst till distriktsköterskor i kommunal hemsjukvård och är överförbar på personer med andra palliativa sjukdomar. Vidare forskning för att få en helhetsbild av den hjärtsviktssjukes vård i hemmet skulle vara att undersöka hur atienternas copingförmåga påverkar deras psykosociala välbefinnande. / Heart failure is one of the most common diseases and a major cause of hospitalization in Sweden. Professional health care provided at home might decrease the number of days of hospitalization for the heart failure patient. If not the heart failure patient´s need for support takes into consideration, there is a risk that professional caregivers in the home do not pay attention to the patient`s need of psychosocial support. The purpose of this study was to describe the heart failure patient's need for psychosocial support while being cared for in the home. A systematic literature review was chosen, 19 articles where selected and analyzed by qualitative content analysis. Two main categories revealed: professional support and informal support. Results of the study describe the supportive services in the form of psychosocial support on heart failure patient experience in the home. The professional care made a holistic assessment of the patient and they noticed psycho-social needs. By enhancing the inherent ability with supportive services, the patient could cope with the mental symptoms of heart failure. For the professional support the involvement of the supporting effort was of paramount importance. If the heart failure patient felt participating in the care, the patients feeling of mastering the disease situation and strengthening of the dignity increased. The literature study caters mainly to district nurses in municipal home care and is transferable to persons with other palliative diseases. Further research is needed to gain an overall picture of the heart failure patient's home care would be to examine how patients' coping, affect their psychosocial well-being.

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.

Current drugs used to treat Congestive Heart Failure target the renin-angiotensin and adrenergic systems. Studies showed increased mortality rates in patients treated with a combination of these medications. Angiotensin-AT1 and ?2-Adrenergic receptors were shown to form receptor heteromers. Blockade of one receptor in the complex can affect the signal transmitted by the other; suggesting that ligand-based therapy is not as selective as we might think. Modulating receptor trafficking after synthesis might prove to be a valid therapeutic strategy. Unfortunately, little is known about receptor assembly and transport from Endoplasmic Reticulum to Plasma Membrane. The objectives of this study are to identify the proteins that participate in the assembly of AT1R-?2AR heteromer and the regulators of the anterograde trafficking of G-Protein Coupled Receptors. This thesis introduces the role of important targets in those poorly understood processes. The identification of such targets could lead to developing better drugs with fewer adverse effects.

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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Tyrimo objektas: ligonių, patyrusių miokardo infarktą, funkcinis pajėgumas, taikant aerobinę treniruotę, jėgos treniruotę ir kombinuotą mankštą (aerobinę + jėgos treniruotę). Darbo tikslas: Nustatyti, kuri kineziterapijos programa – aerobinė, jėgos ar kombinuota – turi didesnį poveikį patyrusiųjų miokardo infarktą funkciniam pajėgumui. Uždaviniai: 1. Įvertinti tiriamųjų per 6 min. nueitą atstumą, ramybės kraujospūdį ir pulsą bei subjektyvius nusiskundimus prieš ir po aerobinės kineziterapijos programos. 2. Įvertinti tiriamųjų per 6 min. nueitą atstumą, ramybės kraujospūdį ir pulsą bei subjektyvius nusiskundimus prieš ir po jėgos kineziterapijos programos. 3. Įvertinti tiriamųjų per 6 min. nueitą atstumą, ramybės kraujospūdį ir pulsą bei subjektyvius nusiskundimus prieš ir po kombinuotos kineziterapijos programos. 4. Palyginti skirtingų kineziterapijos programų poveikį tiriamųjų funkciniam pajėgumui. Hipotezė: kombinuota kineziterapijos programa yra efektyvesnė nei jėgos ar aerobinė atgaunant patyrusiųjų miokardo infarktą funkcinį pajėgumą. Tyrimo metodika. Tyrimas buvo atliktas 2011 m. UAB „Palangos linas“ viešbutyje-reabilitacijos centre. Tyrime dalyvavo 45 patyrę miokardo infarktą asmenys (27 vyrai ir 18 moterų), kurie buvo suskirstyti į 3 grupes: I grupės tiriamiesiems (n=15) – taikyta aerobinė treniruotė, II grupės tiriamiesiems (n=15) – taikyta jėgos treniruotė, III grupės tiriamiesiems (n=15) – kombinuota treniruotė Visi tiriamieji gavo po 10 kineziterapijos... [toliau žr. visą tekstą] / Study subject: functional capacity in patients after heart failure, applying aerobic, strenght and combined training. The aim of the study: To determine which physiotherapy program – aerobic, strenght or combined training - would have a bigger effect on functional capacity in patients after heart failure. Study goals: 1. To determine the distance, made in 6 minutes, rest blood pressure and heart rate, and subjective complaint before and after aerobic training. 2. To determine the distance, made in 6 minutes, rest blood pressure and heart rate, and subjective complaint before and after strenght training. 3. To determine the distance, made in 6 minutes, rest blood pressure and heart rate, and subjective complaint before and after combined training. 4. To compare the effect of different physiotherapy programes on functional capacity in patients after heart failure. Hypothesis: combined training would have the biggest effect in recovery of functional capacity in patients after heart failure than strenght or aerobic training. Study methods: Fourty five patients after heart failure were divided into three groups. The aerobic training program was applied for the first group patients, the strenght training program was applied for the second group patients and the third group patients received the combined training program. 6 minutes walk test, testing of blood pressure and heart rate and subjective questionaire were used to evaluate the functional capacity in... [to full text]

The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms. Age is the biggest risk factor associated with heart failure and therefore we investigated transmural changes in Ca2+ handling and contractile proteins in aging F344 rats before the onset of heart failure. We found that in 22-month old F344 rats there is a region-specific decrease in cardiac troponin I phosphorylation in the sub-epicardium that may contribute to slowed myocyte relaxation in the sub-epicardial cells of the same age. We then investigated the transmural patterns of contractile properties in myocardial tissue samples from patients with heart failure. Force and power output reduced most significantly in the samples from the mid-myocardial region when compared to sub-epicardium and sub-endocardium of the failing hearts. There was a region-specific increase in fibrosis is the mid-myocardium of the failing hearts. Myocardial power output was correlated with key sarcomeric proteins including cardiac troponin I, desmin and myosin light chain-1. The results in this dissertation reveal novel region-specific modifications in contractile properties in aging and heart failure. These transmural effects can potentially contribute to disruption in normal wall motion and lead to ventricular dysfunction.

Sleep disturbance is common in patients with heart failure (HF) and the family caregivers. Sleep disturbance is known as a predictor of poor quality of life (QoL) in individual level. The manner in which patients’ and caregivers’ sleep disturbances influence each other’s QoL has not been determined. The purpose of this dissertation was to investigate the associations of sleep disturbance and outcomes in patients with HF and their primary family caregivers. The specific aims were to: 1) examine whether sleep disturbance of patients and their family caregivers predict their own and their partners’ QoL; 2) examine the mediator effects of depressive symptoms on the association between sleep disturbance and QoL in patients and family caregivers; and 3) provide evidence of the psychometric priorities of the Zarit Burden Interview (ZBI) as a measure of caregiving burden in caregivers of patients with HF. The three specific aims were addressed using secondary analyses of cross-sectional data available from 143 patients with HF and their primary family caregivers. To accomplish Specific Aim One, multilevel dyadic analysis, actor-partner interdependence model was used for 78 patient- caregiver dyads. Individuals’ sleep disturbance predicted their own poor QoL. Caregivers’ sleep disturbance predicted patients’ mental aspect of QoL. For Specific Aim Two, a series of multiple regressions was used to examine the mediation effect in patients and caregivers separately. Depressive symptoms significantly mediated the relationship between sleep disturbance and mental aspect of QoL in patients. The mediation effect was similar in caregivers. For Specific Aim Three, the internal consistency and convergent and construct validity of the ZBI in 124 family caregivers of patients with HF were examined. The results showed that the ZBI is a reliable and valid measure of caregiving burden in this population. This dissertation has fulfilled important gaps in the evidence base for the QoL outcome in patients with HF and caregivers. The findings from this dissertation provided evidence of the importance of monitoring sleep disturbance for better QoL in both patients and caregivers and the importance of assessing caregivers’ sleep disturbance for improving patients’ QoL. It also provided evidence of the importance of managing depressive symptoms when targeting sleep disturbance to improve QoL in both patients and caregivers.