The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic velocities. Using conventional echocardiography we also evaluated whether the hearts of experienced ultra-endurance athletes are larger than the normal upper limit. The central circulation changed in several steps in response to ultra-endurance exercise. Compared to initial levels, VO2 was increased at every time-point measured. The increase was attributed to peripheral adaptations, confirmed by a close correlation between change in VO2 and change in arteriovenous oxygen difference. The first step of the circulatory response was typical of normal (early) cardiovascular drift, with increased HR and concomitantly decreased stroke volume (SV) and oxygen pulse (VO2/HR), occurring over the first 4-6 h. The second step, which continued until approximately 12h, included reversed HR-drift, with normalisation of SV and VO2/HR. When exercise continued for 50 h a late cardiovascular drift was noted, characterised by increased VO2/HR, (indicating more efficient energy distribution), decreased peripheral resistance, increased SV, and decreased work of the heart. Since cardiac output was maintained at all-time points we interpret the changes as physiologically appropriate adaptations. Our findings in Study III point towards a distinction between the clinical/pathological and the physiological/exercise-induced release of cardiac biomarkers. The results imply that troponin and CKMB lack relevance in the (healthy) exercise setting, but that BNP, or NT-proBNP adjusted for exercise duration, might be a relevant indicator for impairment of exercise performance. High levels of NTproBNP, up to 2500 ng · l -1 , can be present after ultra-endurance exercise in healthy athletes without any subjective signs or clinical symptoms of heart failure. However, these high levels of NT-proBNP seemed to be associated with decreased relative exercise performance, and might be an indicator of the cardiac fatigue that has previously been described after endurance exercise. Study IV revealed that the sizes of the hearts (left ventricle) of all of our ultra-endurance athletes were within normal limits. The measurements of peak systolic velocities showed (for group average) no signs of cardiac fatigue even after 6 days of continuous exercise. This discrepancy between ours and other studies, involving e.g., marathon or triathlon, might reflect the fact that this type of exercise is performed at relatively low average intensity, suggesting that the intensity, rather than the duration, of exercise is the primary determinant of cardiac fatigue. / Physiology of Adventure Racing

Bakgrund: Uträkning av vänsterkammarens (VK) volymer (Enddiastolisk volym, EDV; Endsystolisk volym, ESV; Slagvolym, SV) och ejektionsfraktion (EF) går att göra med elektrokardiografi (EKG)-styrd gating vid positronemissionstomografi (PET) med spårämnet 15O-vatten. Metoden behöver utredas noggrannare och optimeras för att kunna introduceras i klinisk rutinverksamhet. Syfte: Syftet med denna studie var att undersöka bildanalys av PET-rekonstruktioner med olika spatial och temporal upplösning i samband med 15O-vatten-PET utförd med EKG-gating, samt jämföra analysutfallen av VK-volymer och EF mot CMR och sinsemellan, för att utreda möjligheten att optimera metoden. Metod: Totalt 25 patienter som genomgått en 15O-vatten-PET, varav n=11 hade undersökts med CMR samma dag, inkluderades. Olika gating-rekonstruktioner med varierande upplösning utfördes retrospektivt och analyserades automatiskt samt manuellt. Analysutfallen för VK-volymer och EF för PET och CM jämfördes statistiskt. Resultat: I studien fanns en stark till mycket stark korrelation mellan PET och CMR för EDV, stark korrelation för ESV, medel till stark korrelation för SV och svag till medel korrelation för EF. Rekonstruktion med 12 gating-bins och 256x256 matrisstorlek hade starkast korrelation för SV och EF. Samtliga PET-rekonstruktioner korrelerade starkt-till mycket starkt med varandra för VK-volymer och EF. Bland-Altman-analyser visade på en god repeterbarhet, framförallt vid manuell analys, för beräkning av EF med 15O-vatten-PET. Slutsats: VK-volymer och EF kan beräknas med 15O-vatten-PET med en repeterbarhet liknande den för andra, mer använda modaliteter. Att använda en högre upplösning än vad som tidigare testats gav högre värden för EF, och starkare korrelation i jämförelse mot CMR. / Background: Calculation of left ventricle (LV)-volumes (End Diastolic Volume, EDV; End Systolic Volume, ESV; Stroke Volume, SV) and ejection fraction (EF) is possible with electrocardiography (ECG)-gated Positron Emission Tomography (PET) using 15O-water, but the method needs to be further investigated and optimized before clinical routine implementation. Purpose: The purpose of this study was to investigate how altered image resolution affects the analysis and values of LV-volumes and ejection fraction on 15O-water-PET and compare the results against Cardiac Magnetic Resonance imaging (CMR) to enable optimization of the PET-method.  Method: In total, 25 patients who previously underwent a 15O-water-PET, where n=11 also performed CMR on the same day were included in the study. Different gating-reconstructions with varying resolution were performed retrospectively and underwent analysis, both automatically and manually.  Results: Correlation analysis found a strong to very strong correlation comparing PET against CMR for EDV, a strong correlation for ESV, a moderate to strong correlation for SV and a weak to moderate correlation for EF. The reconstruction containing 12 gating-bins and a 256x256 matrix size showed the strongest correlation for SV and EF. All PET-reconstructions correlated strong to very strong against each other for all LV-volumes and EF. Bland-Altman-plots showed good repeatability, especially for manual analysis, when calculating EF on 15O-water-PET.  Conclusion: LV-volumes and EF can be calculated on 15O-water-PET, with repeatability close to that of other modalities. Using an increased resolution than previously tested resulted in higher EF and stronger correlation in comparison with CMR.

Cardiovascular diseases have always been the leading cause of global morbidity and mortality. Aortic stenosis, which is a kind of cardiovascular disease has a high prevalence in elderlies that are 75 years and older. Currently, the only available treatment would be valve replacement surgery. Recently, a few studies have risen regarding the potential of extracellular vesicles to reduce the effects of aortic stenosis, hence allowing patients to opt for a non-life-threatening treatment in comparison to a surgical one. The goal within this study is to determine the pro-coagulability of extracellular vesicles (EVs) that were endogenously derived from human blood (patients and healthy individuals) and their effect on the coagulation cascade. This study was performed on cardiac spheroids that were formed through seeding human aortic endothelial cells in an ultra-low attachment 96-well plate for 96 hours. Spheroids were challenged with tumour necrosis factor-alpha (TNFα) for 24 hours prior to EVs incubation for 48 and 72 hours. The effects of EVs on these spheroids were observed in terms of their ability to induce tissue factor activity. There was no significant difference in the tissue factor activity between spheroids incubated with patient derived EVs or healthy individual derive EVs irrespective of TNFα challenge. To conclude, the results of this study were not significant to stipulate that extracellular vesicles are procoagulant. Hence, further research regarding their ability to reduce or rescue the effects of cardiovascular diseases needs to be performed.

Background: Myocardial infarction is caused by an ischemic condition in the heart muscle. Cardiovsacular diseases is one of Swedens largest public health disease were approximatley 12% of the population is affected. The survival rates are increasing in Sweden due to information and preventive care. The health-related quality of life are affected for those surviving. Aim: The aim of the study was to describe patients' experiences of their life quality post myocardial infarction. Method: A qualitative literature-based study were used in order to answer the aim of the study. A total of ten representative studies were analyzed and interpreted to obtain themes. Results: The result was compiled by three main themes and nine sub-themes. Main symptoms reported post myocardial infarction were fatigue, reduced physical capacity and mental state, uncertainty and affected autonomy. Conclusion: Patient’s lifequality were affected due to physical- and psychologial limitations caused by myocardial infarction. The need for information in order to find coping strategies were seen as a necessity by the patients. Acknowledgement and individual supportive care by healthcare providers were considered essential in order to offer person-centered care for those affected.

Background Type 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes. Methods Data from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of  sagittal abdominal diameter. Results Paper 1: Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure. Paper 2: The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV. Paper 3: At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up. Paper 4: Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses. Conclusions Ambulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.

No description available.

För att patienten ska ha optimal chans till överlevnad är det av största vikt att rekommendationer i samtliga delar av kedjan som räddar liv följs. Sjuksköterskan är oftast bland de första på plats vid ett hjärtstopp på en vårdenhet, vilket gör det intressant att belysa vilka faktorer som påverkar överlevnaden efter hjärtstopp på sjukhus. Syftet med litteraturstudien var att belysa faktorer i behandlingen av hjärtstopp på sjukhus som påverkar överlevnaden. Genom en sammanställning och analys av vetenskapligt värderad litteratur utfördes en systematisk litteraturstudie i ämnet. Resultatet visade att en väl fungerande organisation, utbildning, monitorering och följsamhet till riktlinjer var framgångsfaktorer i behandling av hjärtstopp. En hjärt-lungräddningsorganisation behövs, vilken organiserar och kvalitetssäkrar utbildning, rutiner, riktlinjer, utrustning och uppföljning. Utbildning av all personal är en förutsättning för framgångsrik behandling. Sjuksköterskan har möjlighet att identifiera och initiera åtgärder, såsom monitorering, vid ett hjärtstopp på sjukhus för att ge patienten största chans till överlevnad. Följsamheten till rekommendationer är låg med risk för att patientens chans att överleva efter ett hjärtstopp minskas. Hjärtstopp på sjukhus har hittills inte varit föremål för forskning i samma mängd som hjärtstopp utanför sjukhus. Speciellt omvårdnadsforskning om åtgärder där sjuksköterskan kan påverka överlevnaden saknas. / In order to achieve the highest survival among patients suffering from in-hospital cardiac arrest, adherence to treatment guidelines are of utmost importance. A nurse is often among the first person on scene when in-hospital cardiac arrest occurs in a regular ward. For this reason, this study explores the factors that may affect survival. The aim of this literature study was to explore factors that affect survival among patients suffering from in-hospital cardiac arrest. Analysis was made on publications found by a systematic search in peer-reviewed publications in the field. The result emphasis the large impact of structure and organization in order to achieve high quality cardiac arrest treatment. There is a need for a centralized cardiopulmonary resuscitation (CPR) management structure in every hospital. This CPR managing group is vital in organizing guidelines, equipment, training and follow-up on treatment results. Training in CPR of all hospital staff is importance for treatment quality. The nurse has the possibility to identify and modify nursing factors such as monitoring level in order to increase chance of detection and thereby the chance of survival in case of cardiac arrest. Current adherence to treatment guidelines is low leading to lower chance of survival. CPR research has so far focused on out-of-hospital cardiac arrest, less focus has been spent on in-hospital cardiac arrest. In particular nursing science concerning areas were nurses are able to affect outcome is lacking.

Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future. The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome. Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later. In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up. In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage. A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome. In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.

As the occurrence of obesity increases amongst young people, so increases the risk of more people suffering from heart failure as early as during middle age. The aim is to describe the life experiences of middle aged persons living with chronic heart failure. The literature study is based on twelve published, qualitative, and scientifically proved articles derived from MedLine and Cinahl using queries representing the subject, as well as from manual searching in ScienceDirect and LIBRIS. These articles have been analyzed from a life world perspective. Four main themes and four sub themes were identified from the articles' results. The main themes are "The social life", "Quality of life", "Body failing", and "the Economical impact of chronic heart failure". These represent the main areas where the patients feel the greatest loss due to their condition. The discussion reveals the importance of informing the patients of the common prevalence of the feelings described in this study. Also, the nurse should function as a coach for self-care with continuous follow-ups. The result of this study will hopefully increase the understanding of the heart diseased patients' life situations. / I takt med att förekomsten av kraftig övervikt ökar bland unga, ökar även risken för att fler personer drabbas av hjärtsvikt redan i medelåldern. Syftet är att utifrån befintlig forskning beskriva medelålders personers upplevelser av hur det är att leva med kronisk hjärtsvikt. Litteraturstudien baseras på 12 publicerade, kvalitativa och vetenskapliga artiklar efter sökning i MedLine och Cinahl med specifika sökord som representerade ämnet. Manuella sökningar utfördes i ScienceDirect och LIBRIS. Artiklarna har analyserats utifrån ett livsvärldsperspektiv. Ur artiklarnas resultat identifierades fyra teman och sex subteman. Huvudteman är ”Det sociala livet”, ”Livskvalitet”, ”Kroppen sviker” och ”Ekonomiska aspekter”. Huvudteman skildrar patienternas upplevdelser av att leva med kronisk hjärtsvikt. I diskussionen framkommer att det är viktigt för en patient med kronisk hjärtsvikt att få bekräftat att upplevda känslor är vanligt förekommande. Vidare bör sjuksköterskan fungera som en vägledare för egenvård med kontinuerliga uppföljningar. Förhoppningen är att resultatet från denna studie ska öka förståelsen för hjärtsjuka patienter inom ramen för hälso- och sjukvård.

Heart failure is a common disorder and a major cause of illness and death in the population, creating an enormous health-care burden. It is a complex condition, representing the end-point of many cardiovascular diseases. In general heart failure progresses slowly over time and once it is diagnosed it has a poor prognosis which is comparable with that of many types of cancer. The heart has an ability to adapt in response to long lasting increases in hemodynamic demand; the heart conforms its shape and size in order to maintain adequate cardiac output. This process is called remodeling and can be triggered by pathologies such as hypertension or valvular disease. When the myocardial remodeling is maintained chronically it becomes maladaptive and is associated with an increased risk of heart failure. In many cases, heart failure is associated with left bundle branch block (LBBB). This electrical disturbance leads to dyssynchronous left ventricular (LV) contraction and relaxation which may contribute to cardiac dysfunction and ultimately heart failure. Mechanical dyssynchrony can be treated with cardiac resynchronization therapy (CRT). However, many heart failure patients do not demonstrate clinical improvement despite CRT. Blood flow plays an important role in the normal development of the fetal heart. However, flow-induced forces may also induce changes in the heart cells that could lead to pathological remodeling in the adult heart. Until recently, measurement tools have been inadequate in describing the complex three-dimensional and time-varying characteristics of blood flow within the beating heart. 4D (3D + time) flow cardiovascular magnetic resonance (CMR) enables acquisition of three-dimensional, three-directional, time-resolved velocity data from which visualization and quantification of the blood flow patterns over a complete cardiac cycle can be performed. In this thesis, novel 4D Flow CMR based methods are used to study the intraventricular blood flow in healthy subjects and heart failure patients with and without ventricular dyssynchrony in order to gain new knowledge of the ventricular function. Different flow components were assessed in normal heart ventricles. It was found that inflowing blood that passes directly to outflow during the same heartbeat (the Direct Flow component) was larger and possessed more kinetic energy (KE) than other flow components. Diastolic flow through the normal heart appears to create favorable conditions for effective systolic ejection. This organized blood flow pattern within the normal LV is altered in heart failure patients and is associated with decreased preservation of KE which might be unfavorable for efficient LV ejection. Inefficient flow of blood through the heart may influence diastolic wall stress, and thus contribute to pathological myocardial remodeling. In dyssynchronous LVs of heart failure patients with LBBB, Direct Flow showed even more reduced preservation of KE compared to similarly remodeled LVs without LBBB. Furthermore, in LBBB patients, LV filling hemodynamic forces, acting on the myocardium, were more orthogonal to the main flow direction compared to patients without LBBB. Deviation of LV flow forces and reduction of KE preservation and may reflect impairment of LV diastolic function and less efficient ensuing ejection related to dyssynchrony in these failing ventricles. Blood flow patterns were also studied with respect to fluctuations of the velocity of the flow (turbulent flow) in normal and failing LVs. In failing hearts, turbulent kinetic energy (TKE) was higher during diastole than in healthy subjects. TKE is a cause of energy loss and can thus be seen as a measure of flow inefficiency. Elucidating the transit of multidimensional blood flow through the heart chambers is fundamental in understanding the physiology of the heart and to detect abnormalities in cardiac function. The 4D Flow CMR parameters presented in this thesis can be utilized to detect altered intracardiac blood flow and may be used as markers of deteriorating cardiac function, pathological remodeling and mechanical dyssynchrony in heart failure.