Para investigar se estresse oxidativo contribui para a progressão da calcificação/estenose valvar aórtica (VA), avaliamos a produção de espécies reativas de oxigênio (ERO) e efeitos dos antioxidantes tempol e ác. lipóico em modelo de calcificação VA em coelhos. Superóxido, H2O2 e 3-nitrotirosina aumentaram em células inflamatórias e principalmente nos núcleos de calcificação, juntamente com as subunidades p22phox, Nox2 da NADPH oxidase e da proteína dissulfeto isomerase, que co-localizam. PCR mostrou aumento da Nox4 em relação a Nox1. A calcificação foi menor com ác.lipóico e maior com tempol, coicidindo com resultados de modelo in vitro em células musculares lisas. VA humanas estenóticas tiveram aumento semelhante de ERO e da expressão protéica em torno da calcificação. Estresse oxidativo pode contribuir para a progressão da estenose aórtica. / To invetigate whether oxidative stress contributes to aortic valve (AV) calcification/stenosis progression, we assessed reactive oxygen species (ROS) production and effects of antioxidants tempol and lipoic acid in a rabbit AV calcification model. Superoxide, H2O2 and 3-nitrotyrosine increased in inflammatory cells and mainly in calcifying nuclei, coincident with NADPH oxidase subunits p22phox, Nox2 and protein disulfide isomerase, which co-localized. PCR showed switch from Nox1 to Nox4. Calcification was smaller with lipoic acid and greater with tempol, similar to an in vitro smooth muscle cell calcification model results. Human stenotic AV had analogous increase in ROS and protein expression around calcifying nuclei. Oxidative stress can contribute to AV stenosis progression.

Bakgrund: I Sverige avlider varje år cirka 600 män och 200 kvinnor till följd av ett brustet abdominalt aortaaneurysm. Mellan 1.5 och 4.0 procent av alla män över 65 år drabbas av ett abdominalt aortaaneurysm och sedan år 2015 erbjuds samtliga 65-åriga män screening för aortaaneurysm. De som diagnostiseras är således vanligen äldre personer, och i takt med stigande ålder ökar även risken att drabbas av andra sjukdomar. Patientgruppen kan därför vårdas på olika typer av vårdavdelningar, vilket gör att den grundutbildade sjuksköterskan kan möta dessa patienter på många olika vårdinstanser. För att kunna ge en god och personcentrerad vård krävs en förståelse för patienternas upplevelser relaterat till sitt aneurysm samt hur det påverkar det dagliga livet för patienterna.  Syfte: Litteraturöversiktens syfte var att beskriva vuxna patienters upplevelser relaterat till deras abdominala aortaaneurysm, både under konservativ behandling samt postoperativt och hur det påverkar det dagliga livet. Metod: Litteraturöversikten är baserad på tolv vetenskapliga artiklar med kvalitativ studiedesign. Artiklarna hämtades från tre olika databaser med medicin- och omvårdnadsfokus och analyserades därefter induktivt med en förenklad form av metasyntes. Resultat: Fem huvudkategorier och sju underkategorier av upplevelser hos patienter identifierades. Huvudkategorierna var: upplevelser kring behovet av information; upplevelser av att kunna lita på hälso- och sjukvården; oro, rädsla och ångest relaterat till AAA; AAAs påverkan på det dagliga livet; och möjlighet att vara delaktig i vårdprocessen. Konklusion: Litteraturöversikten visade att AAA upplevs med stor variation av patienter. Men framförallt upplever patienter en brist i information och kunskap om sitt AAA där ytterligare stöd, information och kunskap önskas av patienter.  Nyckelord: Abdominalt aortaaneurysm, Dagligt liv, Patienter, Personcentrerad vård, Upplevelser / Background: In Sweden, approximately 600 men and 200 women die each year as a result of a ruptured abdominal aortic aneurysm. Between 1.5 and 4.0 percent of all men over the age of 65 years suffer from an abdominal aortic aneurysm and since year 2015, all 65-years-old men have been offered a screening for aortic aneurysm. Those who are diagnosed are thus elderly and alongside an increasing age, the risk of being subject to other diseases also increases. The patient group can therefore be cared for in different types of care wards, which means that the undergraduate nurse can meet these patients in many different care institutions. In order to be able to provide good and person-centred care, an understanding of the patients' experiences of their aneurysm, and how it affects their daily lives, is required. Aim: The aim of this literature study was to describe adult patients' experiences related to abdominal aortic aneurysm, both during conservative treatment and postoperatively and how it affects daily life. Method: A literature study which is based on twelve scientific articles with qualitative study design. The articles were retrieved from three different databases with a focus on medicine and nursing and were thereafter analysed inductively with a simplified form of metasynthesis. Result: Five main categories and seven subcategories of patient experiences were identified. The main categories were: experiences around the need for information; experiences of being able to trust the health care; worry, fear and anxiety related to AAA; AAA's impact on daily life; and the possibility to be involved in the care process. Conclusion: The literature review shows that AAA is experienced with a large variety of patients. But above all, patients experience a lack of information and knowledge about their AAA where further support, information and knowledge is desired by patients.  Keywords: Abdominal aortic aneurysm, Daily life, Experiences, Patients, Person-centred care.

<p>An abdominal aortic aneurysm (AAA), defined as a pathological expansion of the largest artery in the abdomen, is a relatively common disease that frequently leads to death if rupture occurs. Once diagnosed, clinicians often evaluate the rupture risk based on the maximum diameter of the aneurysm, a limited metric that is not accurate for all patients. In this study, we worked to provide additional distinguishing factors between growing and stable AAAs to aid in clinical rupture risk assessment. We utilized a relatively new murine model that uses surgical application of topical elastase to cause initial aortic expansion, and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water to promote AAA growth. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to obtain and evaluate alternative geometric and biomechanical parameters between 1) growing AAAs, 2) stable AAAs, and 3) non-aneurysmal control mice. Our study confirmed the reproducibility of the model and found reduced strain values, greater tortuosity, and decreased elastin health in mice with aneurysms. We also found expanding murine AAAs to have increased peak wall stress and surface area per length compared to stable aneurysms. The results from this work help provide a better understanding of the growth patterns associated with elastase-BAPN murine aneurysms and demonstrate the capabilities of high-frequency ultrasound. Eventually these data could help lay the groundwork for improving insight into clinical prediction of AAA expansion.</p>

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La physiopathologie de l’anévrysme de l’aorte abdominale (AAA) est multifactorielle. De la plaque athéro-thrombotique jusqu’à l’anévrisme menaçant, les phénomènes hémodynamiques, protéolytiques, oxydatifs et inflammatoires jouent un rôle aussi complexe qu’interdépendant. Aucun traitement pharmacologique n’a fait la preuve de son efficacité. Dans ce travail, nous étudions 2 voies pharmacologiques potentielles, et développons un modèle murin d’exclusion endovasculaire. La rapamycine est utilisée en oncologie. Ses propriétés anti-inflammatoires, antiprolifératives et anti-angiogéniques stabilisaient la progression anévrismale dans un modèle établi d’AAA. L’AZD9668 est un inhibiteur sélectif de l’élastase. Sécrétée par les neutrophiles, cette protéase joue un rôle clé dans la physiopathologie anévrismale. Les propriétés thérapeutiques ont été étudiées sur un modèle murin potentialisé par l’injection systémique de Porphyromonas Gingivalis, entretenant la réaction inflammatoire et protéolytique pariétale. Dans un second temps, nous avons développé un modèle murin d’exclusion endovasculaire. La spécificité de ce traitement a soulevé de nouvelles problématiques, soulignant le rôle crucial de l’activité biologique du thrombus. L’exclusion endovasculaire d’un AAA sur les modèles de grands animaux est complexe et coûteuse. Nous avons ainsi décrit la technique sur un modèle reconnu d’AAA chez le rat. Le traitement pharmacologique des AAAs a démontré son efficacité sur modèles murins, mais est difficilement transposable à l’homme en raison des effets secondaires. Un traitement endoluminal véhiculant un principe actif délivré in-situ permettrait de stabiliser durablement les AAA. / Abdominal aortic aneurysm (AAA) pathophysiology is multifactorial. From the athero-thrombotic plaque to a threatening aneurysm, hemodynamic, proteolysis, oxidation and inflammation play a complex but interdependent role. No pharmacological treatment has yet proved to be efficient. In this work, we study 2 potential pharmacological targets, and develop a murine model of endovascular abdominal aneurysm repair (EVAR). Rapamycine is used in oncology. Its anti-inflammatory, anti-proliferative and antiangiogenic properties stabilized aneurysm progression on an established AAA. AZD9668 is an elastase selective inhibitor. Secreted by neutrophils, this protease plays a key role in aneurysmal pathophysiology. Its therapeutic benefits have been study on a murine AAA model potentiated by Porphyromonas Gingivalis systemic injection, maintaining inflammatory reaction and wall proteolysis. Then, we developed a murine endovascular aneurysm exclusion model. EVAR raised new concern, underlining the crucial role of the thrombus biological activity. Endovascular AAA exclusion on big animals is complex and expensive. We hence described the technic on a rat AAA well known model. Pharmacological AAAs treatment has proved to be efficient on murine models, but is hard to transpose to humans because of systemic side effects. An endoluminal treatment carrying active drugs, and delivered in-situ, could durably stabilize AAAs.

Bakgrund Bukaortaaneurysm är en potentiell farlig sjukdom med en dödlighet på 80-90% vid bristning. I Sverige screenas således alla 65-åriga män med ultraljud för att upptäcka aneurysmen i tid innan den brister och erbjuda männen behandling.  Syfte Syftet med examensarbetet var att utvärdera den interindividuella mätosäkerheten hos legitimerade och erfarna biomedicinska analytiker vid screening av bukaorta med ultraljud på 65-åriga män.  Material och metod Den interindividuella mätosäkerheten har utvärderats hos två par erfarna biomedicinska analytiker (BMA). BMA-paren screenade och registrerade bukaortandiametern på 65-åriga män vid två olika fysiologiska kliniker med metoden leading edge to leading edge (LELE) i anteroposteiror riktning. Analysen av data har genomförts med programmet IBM SPSS Statistics.  Resultat Analysen av data visade ingen signifikant skillnad i mätosäkerhet mellan BMA eller mellan klinikerna. Skillnaden i medelvärde mellan BMA låg på -0,06 mm respektive -0,07 mm. Medianen för skillnaderna av mätresultaten för respektive BMA-par var 0,0 mm (-0,5 til 0,4 mm, 95% CI) och -0,3 mm (-0,6 till 0,5 mm, 95% CI). Mätosäkerheten påverkades inte av BMI.  Slutsatser Utbildade och erfarna BMA som följer samma undersökningsprotokoll uppnår en hög nivå av interindividuell mätsäkerhet vid screening av bukaortaaneurysm med ultraljud.  Nyckelord: Bukarotaaneurysm, biomedicinska analytiker, interindividuell variation, LELE

Bisher existiert keine nicht-invasive/ nicht-operative Therapie der Aortenklappenstenose. Als wichtiger Zeitpunkt für eine präventive Maßnahme, zur Verhinderung der Ausbildung einer hömodynamisch relevanten Aortenklappenstenose, kann das Stadium der Aortenklappensklerose angesehen werden. Dieses frühe Erkrankungsstadium verfügt über zahlreiche pathophysiologische Parallelen zur Atherosklerose, für die eine positive Rolle der Prävention durch körperliche Aktivität erwiesen ist. Ziel dieser Arbeit war die Durchführung der Sekundärprävention der kalzifizierenden Aortenklappenerkrankung durch körperliches Training. Um mögliche Effekte dieser Intervention zu eruieren, wurden LDLR-/--Mäuse mit bereits bestehenden pathologischen Aortenklappenveränderungen über einen Zeitraum von 16 Wochen körperlichem Training unterzogen. Durch morphologische, serumanalytische, immunhistochemische und Genexpressionsanalysen konnte abschließend eine Quantifizierung der Effekte körperlichen Trainings - in der Zielsetzung der Sekundärprävention - realisiert werden.

The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain during lifetime. Like all highly stressed materials, also these biological components undergo fatigue and signs of wear, which impinge upon cardiac output and in the end on health and living comfort of affected patients. Thereby pathophysiological changes of the aortic valve leading to calcific aortic valve stenosis (AVS) as most frequent heart valve disease in humans are of particular interest. The knowledge about changes of the dynamic behavior during the course of this disease and the possibility of early stage diagnosis could lead to the development of new treatment strategies and drug-based options of prevention or therapy. ApoE-/- mice as established model of AVS versus wildtype mice were introduced in an ex vivo artificially stimulated heart model. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behavior of the murine aortic valve and to characterize dynamic properties during artificial stimulation. OCT and high-speed video microscopy with high spatial and temporal resolution represent promising tools for the investigation of dynamic behavior and their changes in calcific aortic stenosis disease models in mice.

Background: Effects of cardiovascular (CV) risk factors on the diameter of the thoracic aorta have not been fully studied. This study examined the associations between CV risk factors and diameter of thoracic aorta. Materials and Methods: Study population comprised of 1273 asymptomatic adults aged ≥18 years from Central Appalachia region of the United States who participated in a coronary artery screening between January 2014 and December 2016. Descriptive statistics and multiple linear regression analyses were performed to examine associations between multiple CV risk factors and diameters of the thoracic aorta. Results: Mean (±SD) age of participants was 57.9±9.7 years; that of body mass index (BMI) was 29.4±5.9. The mean aortic sinus, ascending aorta, and descending aorta diameter were 34.1±4.4 mm, 33.8±4.4 mm, and 26.0±3.6 mm, respectively. Increasing age, being male, and having a higher BMI were associated with wider aortic sinus, ascending aorta, and descending aorta diameters. Hypertension (p < 0.05) and obesity (p < 0.0001) were significantly associated with wider diameter for all measured aortic diameters. Participants with diabetes had wider descending aorta compared to those without (26.6±3.9 mm vs. 25.9±3.5 mm, P = 0.012). Participants who had ever smoked a cigarette had significantly wider descending aorta diameter compared to never smokers (26.3±3.6 mm vs. 25.9±3.5 mm, p = 0.031). Conclusions: The study results suggest that decreasing BMI and management of CV risk factors such as hypertension and modifying behavioral risk factors such as smoking are likely to be emphasized in order to decrease the rate of aortic dilatation and subsequent aortic dissection, if aortic dilatation is detected during a CT scan.