Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction

Objective: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Methods: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Results: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 mu g/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. Conclusions: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats

In this study, we investigated the oxidative stress influence in some prosurvival and proapoptotic proteins after myocardial infarction (MI). Male Wistar rats were divided in two groups: Sham-operated (control) and MI. MI was induced by left coronary artery occlusion. 28-days after surgery, echocardiographic, morphometric, and hemodynamic parameters were evaluated. Redox status (reduced to oxidized glutathione ratio, GSH/GSSG) and hydrogen peroxide levels (H(2)O(2)) were measured in heart tissue. The p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK-3 beta/GSK-3 beta ratios, as well as apoptosis-inducing factor (AIF) myocardial protein expression were quantified by Western blot. MI group showed an increase in cardiac hypertrophy (23%) associated with a decrease in ejection fraction (38%) and increase in left ventricular end-diastolic pressure (82%) when compared to control, characterizing ventricular dysfunction. Redox status imbalance was seen in MI animals, as evidenced by the decrease in the GSH/GSSG ratio (30%) and increased levels of H(2)O(2) (45%). This group also showed an increase in the ERK phosphorylation and a reduction of Akt and mTOR phosphorylation when compared to control. Moreover, we showed a reduction in the GSK-3 beta phosphorylation and an increase in AIF protein expression in MI group. Taken together, our results show increased H(2)O(2) levels and cellular redox imbalance associated to a higher p-ERK and AIF immunocontent, which would contribute to a maladaptive hypertrophy phenotype.

Blockage of Angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation

Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.

The renin-angiotensin system is modulated by swimming training depending on the age of spontaneously hypertensive rats

Aim: To investigate the effects of swimming training on the renin-angiotensin system (RAS) during the development of hypertensive disease. Main methods: Male spontaneously hypertensive rats (SHR) were randomized into: sedentary young (SY), trained young (TV), sedentary adult (SA), and trained adult (TA) groups. Swimming was performed 5 times/wk/8wks. Key findings: Trained young and adult rats showed both decreased systolic and mean blood pressure, and bradycardia after the training protocol. The left ventricular hypertrophy (LVH) was observed only in the TA group (12.7%), but there was no increase on the collagen volume fraction. Regarding the components of the RAS, TV showed lower activity and gene expression of angiotensinogen (AGT) compared to SY. The TA group showed lower activity of circulatory RAS components, such as decreased serum ACE activity and plasma renin activity compared to SA. However, depending on the age, although there were marked differences in the modulation of the RAS by training, both trained groups showed a reduction in circulating angiotensin II levels which may explain the lower blood pressure in both groups after swimming training. Significance: Swimming training regulates the RAS differently in adult and young SHR rats. Decreased local cardiac RAS may have prevented the LVH exercise-induced in the TV group. Both groups decreased serum angiotensin II content, which may, at least in part, contribute to the lowering blood pressure effect of exercise training. (C) 2011 Elsevier Inc. All rights reserved.

Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta

The aim of the present study was to evaluate the effect of overstimulation of beta-adrenoceptors on vascular inflammatory mediators. Wistar rats were treated with the beta-adrenoceptor agonist isoproterenol (0.3 mg(.)kg(-1.)day(-1) sc) or vehicle (control) for 7 days. At the end of treatment, the right carotid artery was catheterized for arterial and left ventricular (LV) hemodynamic evaluation. Isoproterenol treatment increased LV weight but did not change hemodynamic parameters. Aortic mRNA and protein expression were quantified by real-time RT-PCR and Western blot analysis, respectively. Isoproterenol enhanced aortic mRNA and protein expression of IL-1 beta (124% and 125%) and IL-6 (231% and 40%) compared with controls but did not change TNF-alpha expression. The nuclear-to-cytoplasmatic protein expression ration of the NF-beta B p65 subunit was increased by isoproterenol treatment (51%); in addition, it reduced the cytoplasmatic expression of I kappa B-alpha (52%) in aortas. An electrophoretic mobility shift assay was performed using the aorta, and increased NF-kappa B DNA binding (31%) was observed in isoproterenol-treated rats compared with controls (P < 0.05). Isoproterenol treatment increased phenylephrine-induced contraction in aortic rigs (P < 0.05), which was significantly reduced by superoxide dismutase (150 U/ml) and sodium salicylate (5 mM). Cotreatment with thalidomide (150 mg(.)kg(-1.)day(-1) for 7 days) also reduced hyperreactivity to phenylephrine induced by isoproterenol. In conclusion, overstimulation of beta-adrenoceptors increased proinflammatory cytokines and upregulated NF-kappa B in the rat aorta. Moreover, local oxidative stress and the proinflammatory state seem to play key roles in the altered vascular reactivity of the rat aorta induced by chronic beta-adrenergic stimulation.

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury, but their role in chronic kidney diseases is still unknown. More specifically, it is not known whether MSCs halt fibrosis. The purpose of this work was to investigate the role of MSCs in fibrogenesis using a model of chronic renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM rats. Female Wistar rats were subjected to the remnant model, and 2 vertical bar x vertical bar 10(5) MSCs were intravenously administrated to each rat every other week for 8 weeks or only once and followed for 12 weeks. SRY gene expression was observed in female rats treated with male MSCs, and immune localization of CD73(+)CD90(+) cells at 8 weeks was also assessed. Serum and urine analyses showed an amelioration of functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks. Masson`s trichrome and Sirius red staining demonstrated reduced levels of fibrosis in MSC-treated animals. These results were corroborated by reduced vimentin, type I collagen, transforming growth factor beta, fibroblast specific protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression and alpha smooth muscle actin and FSP-1 protein expression. Renal interleukin (IL)-6 and tumor necrosis factor alpha mRNA expression levels were significantly decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were increased. All serum cytokine expression levels were decreased in MSC-treated animals. Taken together, these results suggested that MSC therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal injury. The immunosuppressive and remodeling properties of MSCs may be involved in the decreased fibrosis in the kidney. STEM CELLS 2009;27:3063-3073

Coronary reserve impairment prevents the improvement of left ventricular dysfunction and adversely affects the long-term outcome of patients with hypertensive dilated cardiomyopathy

In hypertension, left ventricular (LV) hypertrophy develops as an adaptive mechanism to compensate for increased afterload and thus preserve systolic function. Associated structural changes such as microvascular disease might potentially interfere with this mechanism, producing pathological hypertrophy. A poorer outcome is expected to occur when LV function is put in jeopardy by impaired coronary reserve. The aim of this study was to evaluate the role of coronary reserve in the long-term outcome of patients with hypertensive dilated cardiomyopathy. Between 1996 and 2000, 45 patients, 30 of them male, with 52 +/- 11 years and LV fractional shortening <30% were enrolled and followed until 2006. Coronary flow velocity reserve was assessed by transesophageal Doppler of the left anterior descending coronary artery. Sixteen patients showed >= 10% improvement in LV fractional shortening after 17 +/- 6 months. Coronary reserve was the only variable independently related to this improvement. Total mortality was 38% in 10 years. The Cox model identified coronary reserve (hazard ratio = 0.814; 95% CI = 0.72-0.92), LV mass, low diastolic blood pressure, and male gender as independent predictors of mortality. In hypertensive dilated cardiomyopathy, coronary reserve impairment adversely affects survival, possibly by interfering with the improvement of LV dysfunction. J Am Soc Hypertens 2010;4(1):14-21. (C) 2010 American Society of Hypertension. All rights reserved.

Upplevelser av att leva med hjärtsvikt : ur patienters perspektiv

Syftet var att utifrån aktuell vetenskaplig litteratur beskriva människors upplevelser av att leva med hjärtsvikt. Sjuksköterskans uppgifter är att planera, genomföra och utvärdera omvårdnaden kring hjärtsviktspatienten. En systematisk litteraturstudie gjordes för att belysa aktuell forskning inom ämnet. Artikelsökningarna gjordes i databaserna PubMed, Blackwell Synergy och Cinahl. För att säkra studiens kvalitet användes kvalitativa och kvantitativa granskningsmallar. Resultatet visade att patienter med hjärtsvikt upplevde oro och stress kring sina symtom. Flertalet beskrev en inre turbulens och en förlorad självständighet. Upplevelserna skilde sig bland könen. De flesta kände sig fysiskt begränsade på grund av tröttheten, vilket ledde till en känsla av social isolering. Stödet från omgivningen varierade. Studierna visade att behovet av omvårdande insatser var stort. Flertalet av patienterna hade försämrad aptit och led av oöverkomlig törst. Många drabbades av andnöd och sömnstörningar som gav konsekvenser i det dagliga livet. Kommunikationsproblem mellan sjukvårdspersonal och patienter förekom. Sjuksköterskan kan genom sina omvårdande insatser och sitt engagemang förbättra patientens situation. Litteraturstudien ger ökad förståelse för livssituationen hos patienter med hjärtsvikt.

När hjärtat sviktar : Information och undervisning med hjälp av sjuksköterskan

Syftet med denna litteraturstudie var att ta reda på hur information och undervisning kan utformas och vara ett bra sätt att förbättra den hälsorelaterade livskvaliteten hos patienter med hjärtsvikt. Femton vetenskapliga artiklar valdes ut genom fulltextdatabasen United States National Library of Medicine (MEDLINE) och Högskolan Dalarnas sökmotor Electronic Library Information Navigator (ELIN). Sökorden som användes var heart failure, quality of life, information/education och nursing i olika kombinationer. Artiklarna som valdes ut granskades med hjälp av modifierade granskningsmallar för att säkerställa att dom var av så hög kvalite som möjligt. Fysisk funktionell förmåga och kunskap om sjukdomen har betydelse för patientens upplevelse av sin hälsorelaterade livskvalitet. Flera av artiklarna i litteraturstudien visar att sjuksköterskeinriktad patientutbildning är effektivt för att förbättra livskvaliteten och den hjälper patienterna att se sina symtom och främjar egenvård. Utbildningen innefattar ofta information om att förändra sin livsstil, fysisk aktivitet, daglig vägning, diet och läkemedelsdosering samt information och undervisning till både patienter och anhöriga om hjärtsvikt och dess symtom. Familj och vänner är ofta ett stort stöd för patienter med hjärtsvikt. Studier visar dock att de ofta har de begränsade kunskaper om vad hjärtsvikt är och hur behandlingen ser ut. De övergripande resultaten av litteraturstudien visar på att databaserad utbildning ger ökad kunskap om hjärtsvikt i jämförelse med sedvanlig utbildning.

Egenvård i nutrition till personer med hjärtsvikt.

Syfte:            Syftet med denna litteraturstudie var att studera hur personer med hjärtsvikt kan få en förbättrad nutrition genom egenvård. Metod:          Studien genomfördes som en litteraturöversikt. Artiklarna söktes via databaserna CINAHL och PubMed. Resultat:       Studiens resultat innehöll 10 artiklar med kvantitativ ansats. En förutsättning för att personer med hjärtsvikt ska klara sin egenvård och ges möjlighet att förbättra sin nutrition är utbildning. Utbildningsmetoder som i föreliggande litteraturstudie har visat sig fungera är att kombinera skriftlig och muntlig utbildning. Undervisningen bör innehålla information om vilken typ av mat personer med hjärtsvikt behöver äta samt varför. En god följsamhet till givna riktlinjer nås genom att ge personer med hjärtsvikt individuellt anpassad information samt att uppföljning sker och information ges kontinuerligt. Slutsats:        Det är mycket viktigt att hälso- och sjukvårdspersonal kombinerar muntlig och skriftlig information vid utbildning inom nutrition riktad till personer med hjärtsvikt för att stärka deras egenvård. Hälso- och sjukvårdspersonal bör se till att kontinuerlig uppföljning sker för att optimera följsamheten.  

Egenvård vid hjärtsvikt- en enkätstudie om vilka egenvårds åtgärder personer med hjärtsvikt säger sig använda i det dagliga livet

Heart failure is an illness that requires life-long treatment and often affects everyday aspects of a person’s life. Self-care is a significant part of the treatment. Good self-care resources make it possible for people with heart failure to make the lifestyle changes they often need to maintain or improve their level of health. Self-care means having knowledge of and being able to recognize the symptoms and signs of deterioration that can occur with heart failure, so that the person can take appropriate measures – and it also means knowing when it is time to seek professional help. The significance of self-care for heart failure has increased and will increase even more in the future, when monitoring one’s condition will be left more and more to the people themselves and those who take care of them. The object of the study was to learn what self-care measures people with heart failure say they apply in everyday life. The quantitative method of a questionnaire study (The European Heart Failure Self-Care Behaviour Scale) was used. Of the 94 people registered at a heart failure unit who were asked to complete the questionnaire, 58 of them consented. The results showed that more than 95% of the people with heart failure applied the recommended self-care measure of taking the medicines prescribed by their doctor. Many also applied the self-care measures of taking a rest during the day (83%) and taking it easy when they felt out of breath (78%). On the other hand, the self-care measures of daily weight control were applied only by 41%, daily exercise by only 48% and salt and fluid restrictions by only 59%. The self-care measures of contacting a doctor/nurse when noticing problems or symptoms of deterioration were applied by only 36% of those who felt out of breath and by only 43% of those who felt increased fatigue. The conclusion is that there is a need to improve the knowledge about and confidence in self-care treatment for people with heart failure. One way of achieving this is to show that people with heart failure check for symptoms and apply measures in their homes as part of the treatment and that this leads to an increased quality of life.

Patient participation : what it is and what it is not

In general, patient participation is regarded as being informed and partaking in decision making regarding one’s care and treatment. This interpretation is common in legislation throughout the Western world and corresponding documents guiding health care professionals, as well as in scientific studies. Even though this understanding of the word participation can be traced to a growing emphasis on individuals’ autonomy in society and to certain dictionary defi nitions, there are other ways of understanding participation from a semantic point of view, and no trace of patients’ descriptions of what it is to participate can be found in these definitions. Hence, the aim of this dissertation was to understand patients’ experience of the phenomenon of patient participation. An additional aim was to understand patients’ experience of non-participation and to describe the conditions for patient participation and non-participation, in order to understand the prerequisites for patient participation. The dissertation comprises four papers. The philosophical ideas of Ricoeur provided a basis for the studies: how communication can present ways to understand and explain experiences of phenomena through phenomenological hermeneutics. The first and second studies involved a group of patients living with chronic heart failure. For the fi rst study, 10 patients were interviewed, with a narrative approach, about their experience of participation and non-participation, as defi ned by the participants. For the second study, 11 visits by three patients at a nurse-led outpatient clinic were observed, and consecutive interviews were performed with the patients and the nurses, investigating what they experience as patient participation and non-participation. A triangulation of data was performed to analyse the occurrence of the phenomena in the observed visits. For paper 3 and 4, a questionnaire was developed and distributed among a diverse group of people who had recent experience of being patients. The questionnaire comprised respondent’s description of what patient participation is, using items based on findings in Study 1, along with open-ended questions for additional aspects and general issues regarding situations in which the respondent had experienced patient participation and/or non-participation. The findings show additional aspects to patient participation: patient participation is being provided with information and knowledge in order for one to comprehend one’s body, disease, and treatment and to be able to take self-care actions based on the context and one’s values. Participation was also found to include providing the information and knowledge one has about the experience of illness and symptoms and of one’s situation. Participation occurs when being listened to and being recognised as an individual and a partner in the health care team. Non-participation, on the other hand, occurs when one is regarded as a symptom, a problem to be solved. To avoid non-participation, the information provided needs to be based on the individual’s need and with recognition of the patient’s knowledge and context. In conclusion, patient participation needs to be reconsidered in health care regulations and in clinical settings: patients’ defi nitions of participation, found to be close to the dictionaries’ description of sharing, should be recognised and opportunities provided for sharing knowledge and experience in two-way-communication.

Patienters upplevelser av vilka faktorer som har betydelse i vården på specialistsjuksköterskeledda hjärtsviktsmottagningar. : En kvalitativ studie

Bakgrund: Hjärtsvikt är ett vanligt och allvarligt tillstånd med hög dödlighet, sjuklighet och försämrad livskvalité. Det beräknas att omkring en kvarts miljon personer i Sverige har kronisk hjärtsvikt. Inrättandet av specialistsjuksköterskeledda hjärtsviktsmottagningar med läkarstöd har förbättrat behandlingen av patienter med hjärtsvikt. Syfte: Syftet med denna studie var att undersöka patienters upplevelser av vilka faktorer som har betydelse i vården på specialistsjuksköterskeledda hjärtsviktsmottagningar. Metod: En intervjustudie med semistrukturerade frågor har använts. En kvalitativ manifest innehållsanalys användes för att analysera det material som framkom vid intervjuerna. Informanterna valdes ut genom ett strategiskt urval. Resultat: Resultatet visade att en fungerande vårdrelation med sjukvården som representerades av specialistsjuksköterska på hjärtsviktsmottagningen samt information för att klara av sin egenvård var av betydelse för informanterna. En god vårdrelation beskrivs av informanterna i studien att den innehåller kontinuitet, tillit till specialistsjuksköterska, samarbete med vårdpersonal, ett bekräftande bemötande samt tillgänglighet vid behov. Konklusion: Vården på specialistsjuksköterskeledda hjärtsviktsmottagningar är betydelsefull för patienters trygghet. Det förefaller viktigt att få veta vem hjärtsviktspatienterna ska kontakta vid behov av stöd och hjälp för att hantera sin situation. Möjligheten att kontakta specialistsjuksköterska när behovet fanns upplevdes betydelsefull. Information om egenvård uppfattades av informanterna som viktigt och som ett stöd i det dagliga livet.

Assessing cardiovascular status: a guide for acute nurses

Many patients admitted to acute care areas of a hospital experience cardiovascular compromise due to conditions such as acute myocardial infarction (AMI), acute coronary syndrome or exacerbations of chronic heart failure. Additionally, patients can experience cardiovascular collapse due to bleeding or cardiac arrhythmias postoperatively. As a consequence, nurses in acute care settings need to be competent in assessing the cardiovascular status of adult patients. The authors provide a framework for assessing the cardiovascular status of patients in acute care settings using the determinants of cardiac output. They provide a brief review of the determinants of cardiac output before discussing both the aims of cardiovascular assessment and how to perform, such an assessment. (non- author abstract)

Ethical dilemmas of a large national multi-centre study in Australia

Aims and objectives: To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study.

Background: Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects.

Methods: The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC.

Results: Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study.

Conclusions: Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services.

Relevance to clinical practice: The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.