Bakgrund: Hjärtsvikt är ett relativt utbrett och allvarligt tillstånd. Återinläggning är vanligt förekommande bland patienter med hjärtsvikt. Patientutbildning är centralt för god vård hos hjärtsviktpatienter, där huvudsyftet med utbildningen är att förbättra patientens egenvård. Syfte: Syftet med studien var att undersöka utbildningsinterventioner utförda av sjuksköterskor som kan minska risken för att patienter med hjärtsvikt återinläggs. Metod: Detta var en litteraturöversikt med en kvantitativ ansats. Litteraturöversikten inkluderade nio kvantitativa RCT studier. Sökningarna gjordes i databaserna Cinahl, the Cochrane Library och PubMed. De valda studierna genomgick kvalitetsgranskning, analys och en sammanställning. Resultat: Fem av nio artiklar kunde visa på en signifikant skillnad mellan grupperna för utfallsmåttet återinläggning efter utbildningsintervention. Gemensamt för studierna var att återinläggning kontrollerades efter en månad. Vissa studier redovisade även ytterligare tidsintervaller. De centrala komponenterna i de olika utbildningsinterventionen och utfallsmåttet återinläggning vid olika tidsintervaller sammanställdes och redovisades i tabell. Konklusion: Utbildningsåtgärder i samband med utskrivning av hjärtsviktspatienter utförda av sjuksköterskor kan vara mångfacetterade och därigenom bestå av flertalet komponenter. Vilka av dessa komponenter i interventionerna som var effektiva och kunde leda till en signifikant skillnad mellan grupperna var oklart. Däremot indikerade fem av nio studier att det kan vara möjligt att minska återinläggning bland patienter med hjärtsvikt genom undervisning. / Background: Heart failure is a common and serious condition. Readmission is frequently common among patients with heart failure. Patient education is central for good care for heart failure patients, where the primary aim of the education is to improve patient self-care. Aim: The aim of the study was to investigate educational interventions conducted by nurses aimed at reducing the risk of readmission among patients with heart failure. Methods: This was a literature review employing a quantitative approach. The literature review included nine quantitative RCT studies. Searches were conducted in the databases Cinahl, the Cochrane Library and PubMed. The selected studies underwent quality assessment, analysis, and synthesis. Results: Five out of nine articles were able to demonstrate a significant difference between the groups in the outcome measure of readmission following educational intervention. A common feature among the studies was that readmission was monitored after one month. Some studies also reported additional time intervals. The central components of the various educational interventions and the outcome measure of readmission at different time intervals were compiled and presented in a table. Conclusion: Education interventions conducted by nurses during the discharge of heart failure patients can be multifaceted and consisting of multiple components. Which of these components were effective and could lead to a significant difference between the groups was unclear. However, five out of nine studies indicated that it may be possible to reduce readmissions among patients with heart failure through education conducted by the nurse.

Bakgrund: En god omvårdnadsrelation mellan anhöriga och sjuksköterskan är grunden för att främja hälsa och välbefinnande hos närstående med hjärtsvikt. Brist på vårdpersonal och ständiga överbeläggningar inom hälso-och sjukvården utmanar sjuksköterskans kommunikativa förmåga med anhöriga och riskerar patientsäkerheten. Syfte: Syftet med studien var att belysa anhörigas erfarenheter av sjuksköterskans omvårdnad i samband med vård av närstående med hjärtsvikt. Metod: Studien genomfördes som en allmän litteraturstudie med en induktiv ansats baserad på nio kvalitativa vetenskapliga artiklar. Data har analyserats med hjälp av Popenoe trestegsmetod för innehållsanalys. Resultat: I litteraturstudien presenteras resultatet baserat på följande tre kategorier: erfarenheter av kommunikation med sjuksköterskan, erfarenheter av sjuksköterskans undervisning och erfarenheter av samarbete med sjuksköterskan. Konklusion: Anhöriga hade både negativa och positiva erfarenheter av sjuksköterskans omvårdnad och bemötande, relaterat till i vilken mån de fick vara tillräckligt delaktiga i vården. Anhöriga upplevde att sjuksköterskan saknade tillräckliga resurser för att säkerställa patientsäkerhet och vårdkvalité i praktiken. / Background: A good nursing relationship between relatives and the nurse is the basis for promoting the health and well-being of relatives with heart failure. The shortage of healthcare workers and constant overcrowding in healthcare challenges the nurse’s communicative ability with relatives and risks patient safety. Aim: The aim of the study was to shed light on relatives’ experiences of the nurse’s nursing care in connection with the care of relatives with heart failure. Method: The study was conducted as a general literature review with an inductive approach based on nine qualitative scientific articles. The data has been analyzed using Popenoes’s three-step method for content analysis. Results: The literature review presents the results based on the following three categories: experiences of communication with the nurse, experiences of the nurse’s teaching and experiences of collaboration with the nurse. Conclusion: Relatives had both negative and positive experiences of the nurse’s care and treatment, related to the extent to which they were able to be sufficiently involved in the care. Relatives experienced that the nurse lacked sufficient resources to ensure patient safety and quality of care in practice.

Bakgrund: Hjärtsvikt är ett vanligt syndrom som drabbar många över hela världen och påverkar de drabbades livsstil och möjligheter. Fysisk aktivitet som behandling kan bidra till en bättre livskvalitet hos personen med hjärtsvikt. Syfte: Syftet med den här studien var att beskriva personers erfarenheter av fysisk aktivitet vid kronisk hjärtsvikt. Metod: En litteraturstudie genomfördes där åtta kvalitativa artiklar valdes ut till resultatet genom en databassökning i CINAHL och PubMed. Författarna genomförde en kvalitativ manifest innehållsanalys på artiklarna. Resultat: Tre huvudkategorier kunde sammanställas av analysen. (1) Information och kunskap påverkar personens förmåga att kunna utföra fysisk aktivitet. (2) Motivation till fysisk aktivitet påverkas av personen själv, socialt stöd och personens omgivning. (3) Fysiologiska upplevelser både hindrar och underlättar fysisk aktivitet. Konklusion: Många som lever med hjärtsvikt känner en rädsla för att utöva fysisk aktivitet, som grundas i de symtom som de upplever av sin hjärtsvikt. Socialt stöd och personens omgivning, samt gruppaktiviteter kan öka motivationen för fysisk aktivitet och övervinna rädslan. Även ökad kunskap om hjärtsvikt hjälper personen hantera sin sjukdom, dess symtom och ökar följsamheten till egenvårdsråd som fysisk aktivitet. Personer med hjärtsvikt som får konkreta råd om fysisk aktivitet utformade efter rekommendationer och professionell uppföljning känner en ökad trygghet och säkerhet i deras utövande av fysisk aktivitet. Vårdpersonal bör anpassa givna råd med personens deltagande och utifrån personens egna sociala och ekonomiska resurser samt hens omgivning.

Bakgrund: Hjärtsvikt är en global och växande folksjukdom med hög dödlighet som ofta medför flera påfrestande symtom för personen. Hjärtsvikt beror på att hjärtat har nedsatt pumpförmåga vilket kan uppkomma av flera olika anledningar. Klassiska symptom för personer med hjärtsvikt är dyspné, trötthet, ödem och viktuppgång. Förutom den medicinska behandlingen är den icke farmakologiska behandlingen med egenvård och livsstilen viktiga delar för att behandla hjärtsvikt. Hjärtsvikt har även ofta negativa konsekvenser på personens vardagliga liv och livskvalitet. Syfte: Syftet var att belysa faktorer som påverkade livskvaliteten hos personer med hjärtsvikt. Metod: En litteraturöversikt där analysen utgick från Whittemore & Knafl (2005) analysmetod. Litteraturöversikten innefattar 15 vetenskapliga artiklar med både kvalitativ och kvantitativ ansats. Sökningarna är gjorda i databaserna CINAHL och PubMed och samtliga artiklar är kvalitetsgranskade där tio artiklar fick mycket god kvalitet och fem artiklar fick god kvalitet. Resultat: I resultatet framkom fyra huvudteman med nio subteman som hade påverkan på livskvaliteten. Dessa huvudteman var psykologiska faktorer, psykosociala faktorer, livsstilsfaktorer och fysiska faktorer. Samtliga faktorer hade olika påverkan på livskvaliteten för personer med hjärtsvikt. Slutsats: Slutsatsen i litteraturöversikten var att det fanns flera faktorer som påverkade livskvaliteten hos personer med hjärtsvikt. Det är av stor vikt att kunna identifiera dessa faktorer för att kunna öka livskvaliteten för dessa personer / Background: Heart failure is a global widespread disease with a high mortality rate. More and more people are falling ill as the population gets older and better treatment options are available. Heart failure is caused by impaired pumping capacity of the heart for various reasons. Classic symptoms for people with heart failure include dyspnea, fatigue, oedema and weight gain. The treatment, in addition to the medical treatment, is focused on nonpharmacological treatment where lifestyle has a significant factor and has been shown to increase the incidence of heart failure. People with heart failure often have a reduced quality of life as the disease usually has a negative impact on everyday life. Aim: The aim was to illuminate factors influencing the quality of life in individuals with heart failure. Method: A literature review where the analysis was based on Whittemore & Knafl (2005) method of analysis. The literature review includes 15 scientific articles with both qualitative and quantitative approaches. The searches are made in two databases CINAHL and PubMed. All articles are quality checked where 10 articles received very good quality and five articles received good quality.  Results: The results revealed four main themes with nine subthemes with different factors that had an impact on the quality of life. These main themes are psychological factors, psychosocial factors, lifestyle factors and physical factors. All factors had a different impact on the quality of life for people with heart failure. Conclusion: The conclusion of the literature review was that there were several factors that affect the quality of life of people with heart failure. It is of great importance to be able to identify these factors in order to increase the quality of life for people with heart failure.

Bakgrund: Hjärtsvikt är en folksjukdom med ett oförutsägbart förlopp som leder till många återinläggningar på sjukhus. Patienterna är i behov av palliativ vård men sjuksköterskorna har bristande kunskap om palliativ vård vid hjärtsvikt. Sjuksköterskor har ett ansvar att lindra patientens lidande och främja en värdig död. Genom att bygga relation med patienten kan sjuksköterskor uppnå det ansvaret. Syfte: Att beskriva sjuksköterskors erfarenheter av att vårda patienter med hjärtsvikt palliativt. Metod: En litteraturbaserad studie baserad på tio kvalitativa artiklar. Resultat: Ur analysen identifierades tre teman; planering av vårdinsatser, kommunicera med patient och anhörig, arbetsmiljö, med nio subteman. Konklusion: Sammanfattningsvis är teamarbete, kommunikation och personcentrerad vård aspekter som sjuksköterskorna anser ökar kvaliteten på palliativ vård vid hjärtsvikt. De upplevde även hinder exempelvis psykisk påverkan, brist på resurser, svårigheter att utföra samtal och kunskapsbrist. Trots erhållen kunskap behöver området beforskas vidare för att kunna utveckla vården. / Background: Heartfailure is a disease with an unpredictable trajectory which leads to many hospital readmissions. These patients need palliative care, but the nurses lack knowledge about palliative heart failure care. Nurses have a responsibility to ease suffering and promote a dignified death. Through building relations with the patient, nurses can achieve this responsibility. Aim: To describe nurses experiences of caring for patients with heart failure palliative. Method: A literature-based study with ten qualitative articles in the result. Findings: From the analysis, three themes were identified; plan care interventions, communicate with patient and relatives, Work Environment with nine subthemes. Conclusion: In summary, teamwork, communication, and person-centered care is aspect which nurses believe increase the quality of heartfailure palliative care. They also experienced barriers, for instance psychological impact, lack of resources, difficulties in palliative conversations and lack of knowledge. Despite obtained knowledge, there is a need for further research in the area to develop the care.

Bakgrund: Hjärtsvikt är en komplex sjukdom som orsakar en mängd olika symptom och sjukdomsrelaterade problem för patienterna, vilket försvårar egenvården. Patienternas egenvårdsförmåga är avgörande för livskvalitén. Därför har sjuksköterskan en viktig funktion i att stödja patienterna i deras egenvård. Syfte: Syftet med studien var att belysa patienters upplevelse av egenvård vid hjärtsvikt. Metod: En allmän litteraturstudie med induktiv ansats. Totalt inkluderades åtta kvalitativa artiklar i litteraturstudien. Resultat: Resultatet utgörs av följande kategorier: Upplevelser av emotionella utmaningar, betydelsen av att använda inre resurser, upplevelser av fysiska begränsningar, patienternas positiva upplevelser av socialt stöd från familj och vänner samt patienternas upplevda behov av stöd från vårdpersonal. Konklusion: Patienter med hjärtsvikt upplever emotionella utmaningar, fysiska begränsningar samt ett behov av mer stöd och information om sin sjukdom för att kunna förbättra egenvården. Stöd från vårdpersonal och anhöriga är en viktig del för att hjälpa patienterna att acceptera och leva med sin diagnos samt för att bedriva egenvård. Genom mer forskning i ämnet kan sjuksköterskorna få mer kunskap kring hur de kan stötta och hjälpa patienterna till att bedriva egenvård. God egenvård bidrar till ökad livskvalitet för individen och minskade kostnader för samhället. / Background: Heart failure is a complex disease that causes a variety of symptoms and disease-related problems for patients which complicates self-care. Patients' ability to perform self-care is crucial for their quality of life. Therefore, nurses have an important function supporting patients in their self-care. Aim: The aim of the study was to highlight patients' experiences of self-care in heart failure. Method: A general literature review with an inductive approach was conducted. A total of eight qualitative articles were included in the literature review. Results: The result consists of the following categories: Experiences of emotional challenges, the importance of using internal resources, experiences of physical limitations, patients' positive experiences of social support from family and friends and patients' perceived needs for support from healthcare professionals. Conclusion: Patients with heart failure experience emotional challenges, physical limitations, and a need for more support and information about their condition to improve self-care. The support from healthcare professionals and relatives is shown to be an important part of helping patients accept and live with their diagnosis, as well as engage in self-care. Through more research on the subject, nurses can gain more knowledge on how to support and assist patients in self-care. Good self-care contributes to increased quality of life for the individual and reduced costs for the society.

Yes / Heart failure affects 26 million people globally, and the optimal management of medicines is crucial for patients, particularly when their care is transferred between hospital and the community. Optimising clinical outcomes requires well-calibrated cross-organisational processes with staff and patients responding and adapting to medicines changes. The aim of this study was to assess the feasibility of implementing a complex intervention (the Medicines at Transitions Intervention; MaTI) co-designed by patients and healthcare staff. The purpose of the intervention was to optimise medicines management across the gaps between secondary and primary care when hospitals handover care. The study objectives were to (1) assess feasibility through meeting specified progression criteria to proceed to the trial, (2) assess if the intervention was acceptable to staff and patients, and (3) determine whether amendment or refinement would be needed to enhance the MaTI. The feasibility of the MaTI was tested in three healthcare areas in the North of England between July and October 2017. Feasibility was measured and assessed through four agreed progression to trial criteria: (1) patient recruitment, (2) patient receipt of a medicines toolkit, (3) transfer of discharge information to community pharmacy, and (4) offer of a community pharmacy medicines review/discussion or medicines reconciliation. From the cardiology wards at each of the three NHS Acute Trusts (sites), 10 patients (aged ≥ 18 years) were recruited and introduced to the 'My Medicines Toolkit' (MMT). Patients were asked to identify their usual community pharmacy or nominate a pharmacy. Discharge information was transferred to the community pharmacy; pharmacists were asked to reconcile medicines and invited patients for a medicines use review (MUR) or discussion. At 1 month following discharge, all patients were sent three questionnaire sets: quality-of-life, healthcare utilisation, and a patient experience survey. In a purposive sample, 20 patients were invited to participate in a semi-structured interview about their experiences of the MaTI. Staff from hospital and primary care settings involved in patients' care were invited to participate in a semi-structured interview. Patient and staff interviews were analysed using Framework Analysis. Questionnaire completion rates were recorded and data were descriptively analysed. Thirty-one patients were recruited across three sites. Eighteen staff and 18 patients took part in interviews, and 19 patients returned questionnaire sets. All four progression to trial criteria were met. We identified barriers to patient engagement with the intervention in hospital, which were compounded by patients' focus on returning home. Some patients described not engaging in discussions with staff about medicines and lacking motivation to do so because they were preoccupied with returning home. Some patients were unable or unwilling to attend a community pharmacy in person for a medicines review. Roles and responsibilities for delivering the MaTI were different in the three sites, and staff reported variations in time spent on MaTI activities. Staff reported some work pressures and staff absences that limited the time they could spend talking to patients about their medicines. Clinical teams reported that recording a target dose for heart failure medicines in patient-held documentation was difficult as they did not always know the ideal or tolerable dose. The majority of patients reported receiving the patient-held documentation. More than two-thirds reported being offered a MUR by their community pharmacists. Delivery of the Medicines at Transitions Intervention (MaTI) was feasible at all three sites, and progression to trial criteria were met. Refinements were found to be necessary to overcome identified barriers and strengthen delivery of all steps of the intervention. Necessary changes to the MaTI were identified along with amendments to the implementation plan for the subsequent trial. Future implementation needs to take into account the complexity of medicines management and adaptation to local context. / This study is funded by the National Institute for Health Research (NIHR) (Programme Grants for Applied Research (Grant Reference Number RP-PG-0514-20009)). The study is also supported by the NIHR Yorkshire and Humber Patient Safety Translational Research Centre.

Foi avaliada a incidência de potencial tardio pelo eletrocardiograma de alta resolução no domínio do tempo em portadores de insuficiência cardíaca congestiva de diferentes etiologias com o objetivo de se estudarem as correlações clínicas e prognósticas entre pacientes com potencial tardio presente e ausente na referida patologia. Foram estudados 288 pacientes com insuficiência cardíaca congestiva, de idades entre 16 a 70 anos (média 51,51; desvio padrão 11,24), 215 do sexo masculino (74,65%) e 73 do sexo feminino (25,35%). As etiologias da insuficiência cardíaca congestiva foram: a cardiopatia hipertensiva em 78 pacientes (27,08%); a cardiopatia isquêmica em 65 (22,57%); a Doença de Chagas em 42 (14,58%); a valvopatia em 12 (4,17%); a cardiomiopatia alcoólica em 9 (3,13%); a cardiomiopatia periparto em 6 (2,08%); a miocardite viral em 3 (1,04%). Em 73 pacientes (25,35%), a etiologia não foi identificada e a cardiomiopatia dilatada foi considerada idiopática. Foram estudados a idade, o sexo, a etiologia da insuficiência cardíaca, as variáveis do eletrocardiograma (área eletricamente inativa e bloqueios de ramo), do ecocardiograma transtorácico (diâmetro do átrio esquerdo, diâmetro sistólico e diastólico do ventrículo esquerdo), da ergoespirometria (consumo máximo de oxigênio) e do eletrocardiograma de longa duração (taquicardia ventricular não sustentada e taquicardia ventricular sustentada). No eletrocardiograma de alta resolução, foram estudadas a duração do QRS standard, a duração do QRS filtrado, a duração do sinal abaixo de 40µV e a voltagem da raiz quadrada dos últimos 40ms. Foi considerado o potencial tardio presente na vigência de dois ou mais dos seguintes critérios: Duração do QRS filtrado >= 114ms; duração do sinal abaixo de 40µV >= 38ms; voltagem da raiz quadrada dos últimos 40ms <= 20µV. Para a análise estatística, foram empregados: o teste de Fisher, para o caso de comparações entre duas variáveis categóricas com 2 categorias cada uma; o teste t-Student, para o caso de comparações entre as médias dos dois grupos para variáveis contínuas; o teste de Man-Whitney (não paramétrico), para o caso de comparações entre os dois grupos quando as variáveis eram provenientes de contagens (número de ocorrências); ANOVA (análise de variância), para o caso de comparações entre mais de dois grupos no caso de variáveis contínuas. Não se observou correlação estatística entre a presença de potencial tardio e as etiologias que levaram à insuficiência cardíaca. Houve correlação entre a duração do QRS standard e a duração do QRS filtrado com a Doença de Chagas e a cardiomiopatia dilatada idiopática. O potencial tardio mostrou correlação significativa com: bloqueios de ramo, duração do QRS maior ou igual a 120ms, consumo máximo de oxigênio, taquicardia ventricular não sustentada, taquicardia ventricular sustentada, morte súbita e mortalidade total. Ao correlacionarmos a presença de potencial tardio com uma má evolução (taquicardia ventricular sustentada, morte súbita e morte por evolução da insuficiência cardíaca) e uma boa evolução (nenhuma das complicações anteriores), foi encontrado diferença significativa no grupo que apresentava potencial tardio presente. Concluímos que pacientes com insuficiência cardíaca congestiva e portadores de potencial tardio presente ao eletrocardiograma de alta resolução têm achado estatisticamente significativo quanto à taquicardia ventricular sustentada e à morte súbita e uma má evolução em relação aos pacientes com potencial tardio ausente. / The incidence of late potential was evaluated by the signal-averaged electrocardiogram in the time domain in patients with congestive heart failure of different etiologies with the goal of studying the clinical and prognostic correlation among patients with the presence and the absence of late potential in the related pathology. 288 patients with congestive heart failure were studied, from 16 to 70 years old (average 51,51; standard deviation 11,24), 215 of males (74.65%) and 73 of females (25.35%). The etiologies of the congestive heart failure were: the hypertensive cardiomyopathy in 78 patients (27.08%); the ischemic cardiomyopathy in 65 (22.57%); the Chagas disease in 42 (14.58%); the valvopathy in 12 (4.17%); the alcoholic heart disease in 9 (3.13%); the delivery cardiomyopathy in 6 (2.08%); the viral myocarditis in 3 (1.04%). In 73 patients (25.35%); the etiology was not identified and the dilated cardiomyopathy was considered idiopathic. The age, sex, and etiology of the cardiac failure, the variable of the electrocardiogram (electric inactive area and bundle branch block), of the transthoracic echocardiogram (left atrium diameter, systolic and diastolic diameter of the left ventricle), of the cardiopulmonary exercise test (maximum consumption of oxygen) and of the Holter monitoring (nonsustained ventricular tachycardia and ventricular tachycardia) have been studied. In the signal-averaged electrocardiogram, the standard QRS duration, the filtered QRS duration, the filtered QRS complex below 40µV and the root mean square voltage of the terminal 40ms were studied. The late potential was considered in the existance of two or more of the following criteria: the filtered QRS duration >= 114ms; the filtered QRS complex bellow 40µV >= 38ms; the root mean square voltage of the terminal 40ms <= 20µV. For the statistic analysis, the Fisher test was used for the case of comparison between two specific variables, each one with 2 categories; the test t-Student was used for the case of comparison between the average of the two groups for continuous variables; the Man-Whitney test, for the case of comparison between the two groups when the variables were proceeding from counting (number of occurrences); the ANOVA (variance analysis), for the case of contrast between more than two groups in the case of continuous variables. Statistic correlation was not observed in the presence of late potential and the etiologies that had to the heart failure. There was correlation between the standard QRS duration and the filtered QRS duration with the Chagas disease and the idiopathic dilated cardiomyopathy. The late potential showed remarkable correlation with bundle branch block, duration of the largest or equal to 120ms QRS, maximum consumption of oxygen, nonsustained ventricular tachycardia, sustained ventricular tachycardia, sudden death and total mortality. When correlating the presence of late potential with a bad evolution (sustained ventricular tachycardia, sudden death and death by evolution of the heart failure) and a good evolution (none of the previous complications), relevant difference was found in the group that presented late potential. To conclude, patients with congestive heart failure and carrying late potential shown by the signal-averaged electrocardiogram have statistically relevant findings in the sustained ventricular tachycardia and the sudden death and a bad evolution in relation to the patients with absent late potential.

Dados recentes do nosso laboratório sugerem que a enzima dipeptidil peptidase IV (DPPIV), uma serino-protease que pode ser encontrada ancorada na membrana celular de diversos tipos celulares ou na forma solúvel no plasma, possui um papel importante na fisiopatologia da insuficiência cardíaca (IC). Mais especificamente, demonstramos que a atividade da DPPIV circulante está associada com piores desfechos cardiovasculares em modelo experimental e pacientes com IC. Ademais, observamos que a inibição crônica da DPPIV atenua o desenvolvimento e/ou a progressão da IC em ratos submetidos à injúria do miocárdio. Entretanto, não é sabido se a inibição desta peptidase é capaz de reverter a disfunção cardiorrenal em ratos com IC estabelecida. Assim, este trabalho teve como objetivo testar a hipótese que a inibição da DPPIV exerce efeitos terapêuticos em ratos com IC. Para tal, ratos com IC foram tratados diariamente com o inibidor da DPPIV Vildagliptina (80 ou 120 mg/kg/dia) ou veículo (HF) durante quatro semanas. Ratos Sham não-tratados foram utilizados como controle. Análises ecocardiográficas demonstraram que ratos HF exibiram área fracional (FAC) menor e tempo de relaxamento isovolumétrico (TRIV) maior que ratos Sham. Por sua vez, o tratamento com a dose maior de Vildagliptina foi capaz de aumentar a FAC e diminuir o TRIV. Esta melhora funcional foi acompanhada por melhoras estruturais, visto que a inibição da DPPIV foi capaz de reduzir a hipertrofia cardíaca e a deposição de colágeno intersticial no miocárdio remanescente de ratos tratados com Vildagliptina em comparação aos ratos HF. Adicionalmente, ratos com IC exibiram maior teor de água nos pulmões, menor excreção urinária de sódio, menor fluxo urinário e menor ritmo de filtração glomerular em comparação ao grupo Sham. Por sua vez, o manuseio renal de sal e água foi completamente restaurado pelo tratamento crônico com 120 mg/kg/dia Vildagliptina. A normalização da função renal induzida pela inibição crônica da DPPIV foi associada com um aumento da expressão do receptor do peptídeo-1 semelhante ao glucagon (GLP-1) e maior ativação da proteína cinase A em córtex renal, isto é, da via de sinalização deflagrada pela ligação GLP-1/GLP-1R. Além disso, os níveis pós-prandiais do GLP-1, principal substrato da DPPIV que exerce ações insulinotrópicas, cardio e renoprotetoras, estavam mais baixos em ratos HF que em ratos Sham. Esta diminuição dos níveis circulantes de GLP-1 (ativo e total) em ratos HF foi acompanhada de intolerância à glicose bem como de maiores níveis plasmáticos de insulina. A inibição da DPPIV com Vildagliptina melhorou a biodisponibilidade e a secreção de GLP-1 após carga oral de glicose. Em conjunto, estes resultados sugerem que a inibição da DPPIV melhora a função cardiorrenal e metabólica de ratos com IC. Além disso, a secreção e a biodisponibilidade do GLP-1 encontram-se prejudicadas em ratos com IC e o tratamento com Vildagliptina é capaz de restaurar a sinalização mediada por este peptídeo. Assim, os inibidores da DPPIV podem ser eficazes não apenas para a prevenção, mas também para o tratamento da insuficiência cardíaca em ratos / Recent data from our laboratory suggest that the enzyme dipeptidyl peptidase IV (DPPIV), a serine protease that can be found anchored in the cell membrane of different cell types or in the soluble form in plasma, plays an important role in the pathophysiology of heart failure (HF). More specifically, we have demonstrated that the activity of circulating DPPIV is associated with poorer cardiovascular outcomes in an experimental model and patients with HF. In addition, we have found that chronic inhibition of DPPIV attenuates the development and/or progression of HF in rats with myocardial injury. However, it is unknown whether the inhibition of this peptidase is able to reverse the cardiorenal dysfunction in rats with established HF. Therefore, this study aimed to test the hypothesis that inhibition of DPPIV exerts therapeutic effects in rats with HF. To this end, HF rats were treated daily with the DPPIV inhibitor vildagliptin (80 or 120 mg/kg/day) or vehicle (HF) for four weeks. Untreated Sham rats were used as controls. Echocardiographic analysis demonstrated that HF rats exhibit lower fractional area change (FAC) and higher isovolumetric relaxation time (IVRT) than Sham rats. On the other hand, treatment with the highest dose of vildagliptin was able to increase FAC and decrease IVRT. These functional improvements were accompanied by structural improvements, since inhibition of DPPIV was also able to reduce cardiac hypertrophy and interstitial collagen deposition in the remaining myocardium of rats treated with vildagliptin rats compared to HF. In addition, HF rats exhibited higher water content in the lungs, lower urinary sodium excretion, lower urinary flow and lower glomerular filtration rate compared to the Sham group. In turn, the renal handling of salt and water was completely restored by chronic treatment with vildagliptin 120 mg/kg/day. Normalization of the renal function induced by chronic inhibition of DPPIV was associated with an increase in the expression of the glucagon like peptide-1 receptor (GLP-1R) and enhanced protein kinase A activation in the renal cortex, the signaling pathway triggered by bind between GLP-1/GLP-1R. In addition, the postprandial levels of GLP-1, the main substrate of DPPIV that exerts insulinotropic, cardio and renoprotective actions, were lower in HF rats than in Sham. This decrease in circulating levels of GLP-1 (active and total) in HF rats was accompanied by impaired glucose tolerance and higher plasma insulin levels. The inhibition of the DPPIV with vildagliptin improved the bioavailability and secretion after an oral glucose load. Taken together, these results suggest that the inhibition of DPPIV ameliorates the cardiorenal and metabolic function of rats with HF. Furthermore, bioavailability and secretion of GLP-1 are impaired in HF rats and vildagliptin is able to restore the signaling mediated by this peptide. Therefore, DPPIV inhibitors can be effective not only in preventing but also for the treatment of HF in rats

Dados recentes do nosso laboratório sugerem que a enzima dipeptidil peptidase IV (DPPIV), uma serino-protease que pode ser encontrada ancorada na membrana celular de diversos tipos celulares ou na forma solúvel no plasma, possui um papel importante na fisiopatologia da insuficiência cardíaca (IC). Mais especificamente, demonstramos que a atividade da DPPIV circulante está associada com piores desfechos cardiovasculares em modelo experimental e pacientes com IC. Ademais, observamos que a inibição crônica da DPPIV atenua o desenvolvimento e/ou a progressão da IC em ratos submetidos à injúria do miocárdio. Entretanto, não é sabido se a inibição desta peptidase é capaz de reverter a disfunção cardiorrenal em ratos com IC estabelecida. Assim, este trabalho teve como objetivo testar a hipótese que a inibição da DPPIV exerce efeitos terapêuticos em ratos com IC. Para tal, ratos com IC foram tratados diariamente com o inibidor da DPPIV Vildagliptina (80 ou 120 mg/kg/dia) ou veículo (HF) durante quatro semanas. Ratos Sham não-tratados foram utilizados como controle. Análises ecocardiográficas demonstraram que ratos HF exibiram área fracional (FAC) menor e tempo de relaxamento isovolumétrico (TRIV) maior que ratos Sham. Por sua vez, o tratamento com a dose maior de Vildagliptina foi capaz de aumentar a FAC e diminuir o TRIV. Esta melhora funcional foi acompanhada por melhoras estruturais, visto que a inibição da DPPIV foi capaz de reduzir a hipertrofia cardíaca e a deposição de colágeno intersticial no miocárdio remanescente de ratos tratados com Vildagliptina em comparação aos ratos HF. Adicionalmente, ratos com IC exibiram maior teor de água nos pulmões, menor excreção urinária de sódio, menor fluxo urinário e menor ritmo de filtração glomerular em comparação ao grupo Sham. Por sua vez, o manuseio renal de sal e água foi completamente restaurado pelo tratamento crônico com 120 mg/kg/dia Vildagliptina. A normalização da função renal induzida pela inibição crônica da DPPIV foi associada com um aumento da expressão do receptor do peptídeo-1 semelhante ao glucagon (GLP-1) e maior ativação da proteína cinase A em córtex renal, isto é, da via de sinalização deflagrada pela ligação GLP-1/GLP-1R. Além disso, os níveis pós-prandiais do GLP-1, principal substrato da DPPIV que exerce ações insulinotrópicas, cardio e renoprotetoras, estavam mais baixos em ratos HF que em ratos Sham. Esta diminuição dos níveis circulantes de GLP-1 (ativo e total) em ratos HF foi acompanhada de intolerância à glicose bem como de maiores níveis plasmáticos de insulina. A inibição da DPPIV com Vildagliptina melhorou a biodisponibilidade e a secreção de GLP-1 após carga oral de glicose. Em conjunto, estes resultados sugerem que a inibição da DPPIV melhora a função cardiorrenal e metabólica de ratos com IC. Além disso, a secreção e a biodisponibilidade do GLP-1 encontram-se prejudicadas em ratos com IC e o tratamento com Vildagliptina é capaz de restaurar a sinalização mediada por este peptídeo. Assim, os inibidores da DPPIV podem ser eficazes não apenas para a prevenção, mas também para o tratamento da insuficiência cardíaca em ratos / Recent data from our laboratory suggest that the enzyme dipeptidyl peptidase IV (DPPIV), a serine protease that can be found anchored in the cell membrane of different cell types or in the soluble form in plasma, plays an important role in the pathophysiology of heart failure (HF). More specifically, we have demonstrated that the activity of circulating DPPIV is associated with poorer cardiovascular outcomes in an experimental model and patients with HF. In addition, we have found that chronic inhibition of DPPIV attenuates the development and/or progression of HF in rats with myocardial injury. However, it is unknown whether the inhibition of this peptidase is able to reverse the cardiorenal dysfunction in rats with established HF. Therefore, this study aimed to test the hypothesis that inhibition of DPPIV exerts therapeutic effects in rats with HF. To this end, HF rats were treated daily with the DPPIV inhibitor vildagliptin (80 or 120 mg/kg/day) or vehicle (HF) for four weeks. Untreated Sham rats were used as controls. Echocardiographic analysis demonstrated that HF rats exhibit lower fractional area change (FAC) and higher isovolumetric relaxation time (IVRT) than Sham rats. On the other hand, treatment with the highest dose of vildagliptin was able to increase FAC and decrease IVRT. These functional improvements were accompanied by structural improvements, since inhibition of DPPIV was also able to reduce cardiac hypertrophy and interstitial collagen deposition in the remaining myocardium of rats treated with vildagliptin rats compared to HF. In addition, HF rats exhibited higher water content in the lungs, lower urinary sodium excretion, lower urinary flow and lower glomerular filtration rate compared to the Sham group. In turn, the renal handling of salt and water was completely restored by chronic treatment with vildagliptin 120 mg/kg/day. Normalization of the renal function induced by chronic inhibition of DPPIV was associated with an increase in the expression of the glucagon like peptide-1 receptor (GLP-1R) and enhanced protein kinase A activation in the renal cortex, the signaling pathway triggered by bind between GLP-1/GLP-1R. In addition, the postprandial levels of GLP-1, the main substrate of DPPIV that exerts insulinotropic, cardio and renoprotective actions, were lower in HF rats than in Sham. This decrease in circulating levels of GLP-1 (active and total) in HF rats was accompanied by impaired glucose tolerance and higher plasma insulin levels. The inhibition of the DPPIV with vildagliptin improved the bioavailability and secretion after an oral glucose load. Taken together, these results suggest that the inhibition of DPPIV ameliorates the cardiorenal and metabolic function of rats with HF. Furthermore, bioavailability and secretion of GLP-1 are impaired in HF rats and vildagliptin is able to restore the signaling mediated by this peptide. Therefore, DPPIV inhibitors can be effective not only in preventing but also for the treatment of HF in rats