Aortic Coarctation: Recent Developments in Experimental and Computational Methods to Assess Treatments for this Simple Condition

Coarctation of the aorta (CoA) is often considered a relatively simple disease, but long-term outcomes suggest otherwise as life expectancies are decades less than in the average population and substantial morbidity often exists. What follows is an expanded version of collective work conducted by the authors\u27 and numerous collaborators that was presented at the 1st International Conference on Computational Simulation in Congenital Heart Disease pertaining to recent advances for CoA. The work begins by focusing on what is known about blood flow, pressure and indices of wall shear stress (WSS) in patients with normal vascular anatomy from both clinical imaging and the use of computational fluid dynamics (CFD) techniques. Hemodynamic alterations observed in CFD studies from untreated CoA patients and those undergoing surgical or interventional treatment are subsequently discussed. The impact of surgical approach, stent design and valve morphology are also presented for these patient populations. Finally, recent work from a representative experimental animal model of CoA that may offer insight into proposed mechanisms of long-term morbidity in CoA is presented

Propagation-based phase-contrast synchrotron imaging of aortic dissection in mice : from individual elastic lamella to 3D analysis

In order to show the advantage and potential of propagation-based phase-contrast synchrotron imaging in vascular pathology research, we analyzed aortic medial ruptures in BAPN/AngII-infused mice, a mouse model for aortic dissection. Ascending and thoraco-abdominal samples from n = 3 control animals and n = 10 BAPN/AngII-infused mice (after 3, 7 and 14 days of infusion, total of 24 samples) were scanned. A steep increase in the number of ruptures was already noted after 3 days of BAPN/AngII-infusion. The largest ruptures were found at the latest time points. 133 ruptures affected only the first lamella while 135 ruptures affected multiple layers. Medial ruptures through all lamellar layers, leading to false channel formation and intramural hematoma, occurred only in the thoraco-abdominal aorta and interlamellar hematoma formation in the ascending aorta could be directly related to ruptures of the innermost lamellae. The advantages of this technique are (i) ultra-high resolution that allows to visualize the individual elastic lamellae in the aorta; (ii) quantitative and qualitative analysis of medial ruptures; (iii) 3D analysis of the complete aorta; (iv) high contrast for qualitative information extraction, reducing the need for histology coupes; (v) earlier detection of (micro-) ruptures

Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall structure and elastic fiber integrity were normal in resistance/muscular arteries (renal, mesenteric, and saphenous). Elastin cross-linking and total elastin content were unchanged in large or small arteries, whereas elastic fiber architecture was abnormal in large vessels. While the E57K mutation did not affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of mutant animals compared to wild-type arteries but equivalent in mesenteric arteries. We found a differential role of FBLN4 in elastic fiber assembly, where it functions mainly in large conduit arteries. These results suggest that elastin assembly has different requirements depending on vessel type. Normal levels of elastin cross-links in mutant tissue call into question FBLN4\u27s suggested role in mediating lysyl oxidase-elastin interactions. Future studies investigating tissuespecific elastic fiber assembly may lead to novel therapeutic interventions for ARCL1B and other disorders of elastic fiber assembly. 2017 © The Authors, some rights reserved

Biomechanical analysis of Ascending Thoracic Aortic Aneurysm (ATAA)

According to the reports of the World Health Organisation (WHO), cardiovascular diseases are the number one cause of death worldwide. Specifically, arterial disease and degeneration are the major reasons for cardiovascular death and disability. Because these diseases are dependent on the changes of the mechanical properties of the arterial wall, it is very important to know as much as possible about the structural composition of arteries. The human aorta is the biggest artery in the body and consists of three main parts, ascending aorta, aortic arch and descending aorta. The walls of the arteries consist of three layers, the intima, media and adventitia, where each of the layers has different physiological functions and therefore distinct mechanical properties. These were investigated using, i.e., uniaxial tensile, inflation or planar biaxial-testing. Purpose of this thesis was to apply the biomechanical approach by mean of numerical and experimental test referring to patient-specific aortic geometries with ascending thoracic aortic aneurysms. However, despite the ample literature and the related scientific and industrial activity in this field, many different phenomena are not yet consolidated. The PhD Thesis is then divided into two main sections: the first is composed by a brief introduction on ATAA, with some background about mechanical properties of soft tissues, the evolution of the constitutive model, some remarks of the continuum. The second section of the thesis is based on the different research activities developed during the PhD

Characteristics of thoracic aortic aneurysm rupture in vitro

International audienceAscending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissection. To accurately evaluate the rupture risk, one must know the local mechanical conditions at the rupture site and understand how rupture is triggered in a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the location conditions. In this work, we employed a previously established pointwise identification method to characterize wall stress, strain, and property distributions to a sub-millimeter resolution. Based on the acquired field data, we obtained the local mechanical properties at the rupture site in nine ATAA tissue samples. The rupture stress, ultimate strain, energy density, and the toughness of the tested samples were also reported. Our results show that the direction of the rupture is aligned with the direction of maximum stiffness, indicating that higher stiffness is not always related to higher strength. It was also found that the rupture generally occurs at a location of highest stored energy. As a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the recruitment of collagen fibers in the deformation of the tissue is probably essential in ATAA rupture

Biomechanical and biochemical properties of the thoracic aorta in warmblood horses, Friesian horses, and Friesians with aortic rupture

Background: Thoracic aortic rupture and aortopulmonary fistulation are rare conditions in horses. It mainly affects Friesian horses. Intrinsic differences in biomechanical properties of the aortic wall might predispose this breed. The biomechanical and biochemical properties of the thoracic aorta were characterized in warmblood horses, unaffected Friesian horses and Friesians with aortic rupture in an attempt to unravel the underlying pathogenesis of aortic rupture in Friesian horses. Samples of the thoracic aorta at the ligamentum arteriosum (LA), mid thoracic aorta (T1) and distal thoracic aorta (T2) were obtained from Friesian horses with aortic rupture (A), nonaffected Friesian (NA) and warmblood horses (WB). The biomechanical properties of these samples were determined using uniaxial tensile and rupture assays. The percentages of collagen and elastin (mg/mg dry weight) were quantified. Results: Data revealed no significant biomechanical nor biochemical differences among the different groups of horses. The distal thoracic aorta displayed an increased stiffness associated with a higher collagen percentage in this area and a higher load-bearing capacity compared to the more proximal segments. Conclusions: Our findings match reported findings in other animal species. Study results did not provide evidence that the predisposition of the Friesian horse breed for aortic rupture can be attributed to altered biomechanical properties of the aortic wall

Tissue Engineering: Proposed Graft for Aortic Aneurysms

The aorta is the main vessel exiting the heart, providing oxygenated blood to the systemic circulatory system. Because of its close proximity to the heart, the aorta must withstand and absorb high pressures. Not surprisingly, one of the most common problems associated with the aorta is due to this high-pressure environment, that being an aortic aneurysm. An aortic aneurysm is a rupture in a portion of the aortic wall that can potentially lead to death. To repair an aortic aneurysm, there are two surgeries, open chest surgery and endovascular aneurysm repair (EVAR), both of which insert stent grafts into the aorta to exclude the aneurysm. Complications can arise from either of these techniques or the stent graft used for repair. An autologous native vessel would be best in mimicking the native aorta, but given the current and near-future research, a biological stent graft could reduce the complications associated with the current procedures and stent grafts