Dissection aortique | EPFL Graph Search

La dissection aortique est une affection rare et grave caractérisée par l'irruption de sang à l'intérieur de la paroi de l'aorte. Elle constitue une déchirure ou porte d'entrée, par laquelle le sang sous pression entre et décolle les feuillets superposés qui constituent la paroi élastique de l'aorte. La dissection de ces feuillets peut s'étendre sur une longue portion de l'aorte ascendante, la crosse aortique et/ou l'aorte descendante. Elle constitue une urgence chirurgicale. On utilise parfois le terme d'anévrisme disséquant. Épidémiologie Son incidence annuelle est d'environ 3 cas pour . Elle semble augmenter. Le principal facteur de risque est l'hypertension artérielle, surtout si elle n'est pas équilibrée. Deux tiers des dissections sont de type A (concernant l'aorte ascendante) et un tiers de type B (aorte descendante). Outre l'HTA, la dilatation de l'aorte ascendante est un facteur de risque important, surtout pour les dissections de type A

The onset of cardiovascular disease in mice: an image-based, computational-experimental approach

Lydia Aslanidou

In a number of cardiovascular diseases, the paucity of longitudinal human data hinders our understanding of disease evolution and forestalls the discovery of new therapeutic strategies. We therefore heavily rely on animal models to elucidate the mechanisms that govern disease development. Nonetheless, the reference mouse arterial physiology and hemodynamics of its systemic circulation have yet to be described. But preclinical research is not limited to healthy mice; it helps decode the elusive etiology of potentially deadly pathologies such as aortic aneurysms and dissections. A key question is: Why are these pathologies so location-specific? In humans, abdominal aortic aneurysms affect the infrarenal aorta and aortic dissections form in the thoracic aorta. Inversely, in the most commonly used mouse model of this field, aortic dissections preferentially form in the suprarenal abdominal aorta but reasons for such localization remain unknown in humans and mice. In Chapter 1 we aimed to fill the knowledge gap of mouse hemodynamics, by translating an existing 1D model of the human arterial circulation to the healthy mouse. The model combines a broad range of literature data with a detailed description of the murine vasculature. Model predictions of pressure and flow were validated against pressure, velocity and diameter measurements from a large independent dataset of mice. This versatile tool can be used to simulate pathology and facilitate the implementation of the 3R's principle in research practice. Our next steps aimed to unravel the origins of site-specific aortic dissections in the mouse model of Angiotensin II infusion. Initially, we imaged the inceptive stage of disease to understand what happens in the suprarenal mouse aorta. Then, we explored why both from a biomechanical and a mechanobiological standpoint. In Chapter 2, we use high-resolution synchrotron imaging to characterize the early morphology of the suprarenal aorta in mice infused with Angiotensin II, prior to overt dissecting events. We found that the primary damage of the wallâs microstructure preferentially occurs around two major side branches of the aorta. After evidence of this direct involvement of side branches in disease onset, we investigated the underlying reasons from two distinct perspectives. In the synchrotron-based computational study of Chapter 3, we hypothesized that biomechanical forces expose branching sites to early vascular injury. We used an in-house framework which enables a. computational structural mechanics of the aortic wall using mouse-specific geometries, and b. mouse-specific validation to indicate whether high mechanical strain spatially coincides with microstructural defects. Branch-related hotspots of strain co-localized with early damaged microstructure, thus pointing towards a mechanically-driven mechanism that nucleates around the aortic branches. In Chapter 4 we explored from a mechanobiological perspective if the suprarenal aorta's vascular function changes prior to dissection. We found a regional variation: both the contractile and the endothelial function were severely compromised in the suprarenal aortaâs dissection-prone segment, but only mildly so in its dissection-protected segments. Surprisingly, vascular function was largely preserved in the adjacent side branches, creating a local discontinuity in the profile of contractile capacity between the (diseased) aorta and the (non-diseased) branches.

EPFL2019

p-Aminobenzamidine attenuates cardiovascular dysfunctions in spontaneously hypertensive rats

Allancer Divino De Carvalho Nunes, Fabiana Pereira Da Costa Fraga, Nikolaos Stergiopulos

Aims:Diminazene aceturate, a putative ACE2 activator, is susceptible to cleavage resulting in the formation of paminobenzamidine (PAB). This study aimed to investigate the effects of PAB in addressing cardiovascular dysfunctions in spontaneously hypertensive rats (SHR). Main methods:Acute effects of PAB on mean arterial pressure (MAP), heart rate (HR), and aortic (AVC) and mesenteric vascular conductance (MVC) were evaluated in anesthetized SHR. Isolated aortic rings and the Langendorff technique were used to investigate the acute and chronic effects of PAB in the artery and heart. Chronic treatment with PAB (1 mg/kg, gavage) was carried out for 60 days. During this period, systolic blood pressure (SBP) and HR were measured by tail-cuff plethysmography. After the treatment, the left ventricle was collected for histology analyses, western blotting, and ACE2 activity. Key findings:Bolus infusion of PAB acutely reduced MAP and increased both AVC and MVC in SHR. Additionally, PAB induced coronary and aorta vasodilation in isolated organs from Wistar and SHR in an endothelialdependent manner. The chronic PAB treatment in SHR significantly attenuated the increase of SBP and improved the aorta vasorelaxation induced by acetylcholine and bradykinin-induced coronary vasodilation. In addition, chronic treatment with PAB attenuated the cardiomyocyte hypertrophy and extracellular matrix deposition in hearts from SHR. PAB did not alter the protein expression of the AT1, AT2, Mas, ACE, ACE2, or ACE2 activity. Significance:PAB induced beneficial effects on cardiovascular dysfunctions induced by hypertension, suggesting that this molecule could be used in the development of new drugs for the treatment of cardiovascular diseases.

PERGAMON-ELSEVIER SCIENCE LTD2022

A systematic review and meta-analysis of the efficacy of aortic anastomotic devices

Dimitrios Schizas, Nikolaos Stergiopulos

Objective: One of the factors contributing to complications related to open repair of the aorta is the construction of a hand-sewn anastomosis. Aortic anastomotic devices (AADs), such as the intraluminal ringed graft (IRG), and the anastomotic stenting technique have been developed to perform a sutureless and less complicated anastomosis. This study performed a systematic review and meta-analysis of the literature reporting clinical use of AADs and aimed to assess, primarily, the effect of each device on 30-day overall and operation-related mortality and aortic cross-clamping time and, secondarily, the rate of successful two-sided application of the IRG device and the operation-related morbidity for each device. Methods: An electronic search was performed using MEDLINE, Scopus, ScienceDirect, and Cochrane Library by two independent authors. Our exclusion criteria included studies incorporating fewer than three patients and studies reporting results solely from animals or in vitro testing, results solely from end-to-side anastomosis, and results solely from endarterectomy procedures. The last search date was February 1, 2018. Results: A total of 41 studies were identified that reported outcomes for the use of three different device types: IRG, anastomotic stenting technique, and surgical staplers. The last two types were classified together as the non-IRG group. The meta-analysis included 27 studies with 50 cohorts incorporating 1260 patients. The median age of the incorporated patients was 61.4 years (range, 51-73 years), and 68.9% were male. The operations were performed for the treatment of acute aortic dissection in 82.3%. The pooled overall 30-day mortality rate varied by device type; IRG devices had a mean rate of all-cause mortality of 9.71%, whereas non-IRG devices were associated with a significantly (I-2 = 15.78%; P for Cochrane Q test

MOSBY-ELSEVIER2019