Biomechanical changes in abdominal aortic aneurysms involve a prolonged post-failure phase.

Expanding the Radiologist's Arsenal against Abdominal Aortic Aneurysms, a Versatile Adversary.

Wall stress distribution on three-dimensionally reconstructed models of human abdominal aortic aneurysm

Exercise, Vascular Health, and Abdominal Aortic Aneurysms

Aortic diseases are common in many populations and are receiving increasing research focus. There are a broad spectrum of aortic diseases that occur in specific regions and appear to have different causes. For example, abdominal aortic aneurysms (AAAs) are most common in aged men.1 In contrast, many forms of thoracic aortic aneurysms (TAAs) occur early in life with a strong genetic basis and no sex discrimination.2 Both aortic aneurysms are amenable to surgical repair. Although surgical approaches have become increasingly sophisticated and less invasive,3 there remains an urgent need to determine factors that predispose to susceptibility and to divert treatment from surgical to medical approaches.4,5 This switch to medical treatment will require an increased knowledge of the mechanisms for several facets of aneurysms that cover the span of initiation, progression, and rupture. In this regard, many recent publications in ATVB have provided further insight into established pathways contributing to aneurysm development such as proteolysis, inflammation, and attenuation of the medial smooth muscle cell population, and a few publications have raised the possibility of new pathways such as adipokines and mineralocorticoid signaling. This article highlights these recent publications within a brief context of the literature. Cigarette smoking remains the major risk factor for development and progression of AAAs.6,7 Several experimental studies have demonstrated that smoke exposure augments AAA induced in mice by either subcutaneous angiotensin II (AngII) infusion or intra-aortic elastase perfusion.8,9 However, it is unclear whether cessation of smoking impacts the development of AAAs. The study of Jin et al10 demonstrated that cessation of cigarette smoking exposure did not immediately decrease the augmentation of AAAs. This sustained effect was attributable to regulation of leukocytic metabolism. Also of note is that cigarette smoking–induced augmentation of AAAs was unaffected …

Rupture of abdominal aortic aneurysm (AAA) is currently the 13th leading cause of death in the US and represents a mechanical failure of the diseased aortic wall. Therefore, accurate estimation of the wall stress distribution in AAA may be a clinically useful tool to predict their risk of rupture [1]. A necessary precursor to an accurate stress analysis is an appropriate representation of the constitutive behavior of the AAA wall. Many previous biomechanical analyses of AAA have employed a linearly elastic constitutive behavior [2,3]. However, we have shown that the AAA wall is nonlinearly elastic [4] and undergoes large strain in-vivo [5]. With this as motivation, we recently developed an isotropic, nonlinearly elastic, large strain constitutive model for AAA wall based on uniaxial tensile testing data [6]. The assumption of isotropy was not validated, however. Utilization of an isotropic material symmetry in models of anisotropic structures may lead to significant errors in stress distribution [7]. Indeed, experiments suggest that the nonaneurysmal aorta is anisotropic (orthotropic) [8,9], but the material symmetry of AAA is not presently known. Moreover, most of the previous work investigating the material symmetry of aorta has been performed on animal tissue. To evaluate the anisotropy of aortic tissue, biaxial experimentation is necessary. There has been very little published work involving the biaxial experimentation of human aortic tissue, and none for AAA tissue. We present here a preliminary evaluation of the biaxial mechanical behavior of human aneurysmal and nonaneurysmal abdominal aorta.

Intermediate Pressure-Normalized Strain Values Are Associated With Increased Abdominal Aortic Aneurysmal Growth Rates

Introduction: Solid evidence is not available on the ideal technique of surgical repair (open or endovascular) of noninfrarenal abdominal aortic aneurysms. Objective: Our aim was to analyze the postoperative effect of mortality and the level of proximal cross-clamping of the patients who underwent open surgical aortic repair of non-infrarenal abdominal aortic aneurysms with intact wall. Method: This is a retrospective, single-centre study, which reviews the results of open surgical repair, performed for intact non-infrarenal abdominal aorta aneurysms between 2005 and 2017. Aneurysms were analyzed in two groups, based on the level of aortic cross-damping: juxta-pararenal aortic aneurysm group with inter- or suprarenal aortic cross-clamping and suprarenal aortic aneurysm group with supraceliac aortic cross-clamping. Primary endpoints were 30-day, 1-, 2- and 5-year mortality. Secondary endpoints were postoperative acute kidney injury, including hemodialysis, and major postoperative complications. Results: In our clinic, 94 patients underwent open surgical aortic repair with cross-clamping above at least one renal artery. The median follow-up was 3.14 (1.55-5.00) years. The overall 30-day, 1-, 2- and 5-year mortality were 9%, 20%, 27% and 48%, respectively. The mortality was significantly lower in the juxta/pararenal abdominal aortic aneurism group at 30 day and 1 year. The overall perioperative incidence of acute kidney injury was 54% and 30% at discharge. Significantly more in-hospital acute renal dysfunction was noticed in the patients with suprarenal aortic aneurysm than with juxta/pararenal aneurysm, however, the difference was not significant at discharge. Major postoperative complications were more frequent in the suprarenal aneurysm group. Conclusion: Open surgical repair of abdominal aortic aneurysms with supraceliac aortic cross-clamping is associated with significantly higher morbidity, early and mid-term mortality than the repair of juxta/pararenal aneurysms. Chronic kidney disease and major postoperative complications are independent factors of mid- and long-term mortality.

In vivo analysis of mechanical wall stress and abdominal aortic aneurysm rupture risk

Abdominal Aortic Aneurysm Rupture Risk Prediction Based on Computer-aided Vascular Wall Stress Assessment Using Finite Element Method – The Future of Decision Making Process

Abdominal aortic aneurysm (AAA), and other cardiovascular disease ar likely associated with changes in mechanical properties of the aortic wall These properties depend mainly on the composition of the aortic wall. Since wall composition changes when AAA are present, it appears probable tha mechanical properties of AAA wall tissue may differ from those of non AAA wall tissue. The objective of this study was to evaluate the differences between AAA and non-AAA wall tissue regarding ultimate strength (σu and modulus of elasticity (E) in the circumferential (cir) and longitudina (Ion) directions. Tensile strength tests were performed in tissue samples obtained from patients during autopsy (non-AAA). or surgery (AAA), using an INSTRON tensile testing machine (model 1122. Instron Corp., Canton MA). Strain rate was 10 mm/min, and sectional area was calculated assuming constant volume and Poisson's ratio of 0.50. Curve fittings were done on a PC using Microsoft ®Excel 97. Results: 22 non-AAA samples from 11 patients, age 59.4 ± 9.8 yr (mean ± SD), and 44 AAA samples from 22 patients, age 58.8 ± 12.3 yr (mean ± SD) were tested. For non-AAA tissue σlon = 1702 ± 57 kPa, σcir = 940 79 kPa, Elon = 1680 ± 76 kPa. Ecir = 1055 ± 59 kPa. For AAA tissue σlon = 1143 ± 67 kPa, σcir = 66 ± 62 kPa, Elon = 1356 ± 87 kPa, Eci = 966 ± 46 kPa. (See Figure). Both σ and E were significantly lower (< 0.05) in AAA tissue than in non AAA tissue. Furthermore, both σ and E were significantly lower in the cir than in the lon direction (p < 0.05). in non-AAA and in AAA tissue.FigureIn conclusion, these experiments show evidence that ultimate strength and modulus of elasticity are significantly reduced in AAA wall tissue. In addition, these properties are significantly lower in the circumferential direction than in the longitudinal direction for both AAA and non-AAA tissue. Therefore, anisotropy and differences between non-AAA and AAA tissue should be taken into account to optimize computational models of AAA wall stress and deformation.

Peak wall stress measurement in elective and acute abdominal aortic aneurysms

Chronic inflammation driven by prostaglandin E 2 (PGE 2 ) is a basis for vascular diseases such as abdominal aortic aneurysm (AAA). We have reported that PGE 2 receptor, EP4, is responsible for AAA progression. However, precise molecular mechanisms are unknown. Since EP4 expression was upregulated in smooth muscle cells (SMCs) in human AAA, we hypothesized that EP4 in SMCs promotes vascular inflammatory responses in AAA. Methods and Results: EP4 transgenic mice (EP4-Tg) in which EP4 is overexpressed selectively in SMCs under SM22α promoter were generated using Cre-loxP system. Neither EP4-Tg nor littermate non-transgenic mice (Non-Tg) exhibited hypertension, hyperlipidemia, or vascular anomaly at basal condition (male, 12-16 weeks-old). Angiotensin II (AngII) infusion (1.0μg/kg/min) caused AAA rupture-related death in all the EP4-Tg around day14 of infusion, while no AAA were observed in Non-Tg until day28 ( n =6-7, P &lt;0.001). To elucidate initial events leading to AAA, the aortae were analyzed at day4 of AngII infusion, at which no AAA was observed. In EP4-Tg aortae, MMP-9 activity was induced ( n =6-7, P &lt;0.05) and IL-6 production was upregulated (5.0±1.8-fold vs. Non-Tg, n =6-7, P &lt;0.05). FACS analysis showed that infiltration of Ly6C hi inflammatory monocytes was enhanced in EP4-Tg aortae, coinciding with the emergence of MMP-9 expression in resident macrophages but not in Non-Tg counterpart (n=4, P &lt;0.01). IL-6 expression was detected primarily in SMC layer in EP4-Tg by immunohistochemistry. Administration of IL-6R antibody (MR16-1, 10mg/kg/2days) in vivo inhibited AngII-induced infiltration of Ly6C hi monocytes (0.3±0.1-fold, n =4, P &lt;0.05) and AAA rupture in EP4-Tg ( n =6, P =0.06). Administration of EP4 antagonist (ONO AE3-208, 0.1mg/kg, BID) also inhibited AngII-induced AAA in EP4-Tg ( n =8, P =0.05). In vitro , EP4 stimulation induced more abundant IL-6 production in EP4-Tg aortic SMCs than Non-Tg SMCs (33.0±4.8-fold, n =4, P &lt;0.001), which was attenuated by PKA inhibitor or TAK1 inhibitor. Immunohistochemistry showed abundant expressions of IL-6 and phosphorylated TAK1 in EP4-positive human AAA but not in non-aneurysmal aorta. Conclusion: PGE 2 -EP4 signaling in SMCs initiates inflammatory reaction and AAA formation via upregulation of IL-6.

Comments regarding ‘The Influence of Wall Stress on AAA Growth and Biomarkers’

The mechanical role of thrombus on the growth rate of an abdominal aortic aneurysm

In vivo imaging of vascular disease models has been largely underutilized, but it can greatly benefit cardiovascular research. An improved understanding of the development of the angiotensin II (AngII) apolipoprotein E knockout model of abdominal aortic aneurysms (AAAs) could help patients with this life-threatening disease. The objective of this study was to investigate the early hemodynamic, biomechanical, and volumetric changes in AngII AAAs using high-frequency ultrasound. Five male apolipoprotein E-deficient C57BL/6J mice were subcutaneously implanted with AngII-loaded miniosmotic pumps (1000 ng/kg/min) and screened for appearance of AAAs. We acquired imaging data of the morphology, pulsatility, and blood flow profiles in newly formed AAAs over 7 days. We found that biomechanical and hemodynamic changes occurred during initial AAA formation alongside an increase in AAA volume. Average AAA volume increased by 140±24% between baseline and AAA diagnosis, while true lumen volume decreased by 46±12% due to formation of a focal dissection. The resulting intramural thrombus evolved in shape and volume but with variability between animals. Regional differences in blood flow velocity were apparent down the length of the largest AAAs and mean blood flow velocity significantly increased by 150±42% upon initial aortic expansion and true lumen narrowing. Mean velocity decreased over 7 days as the total AAA volume increased. Circumferential cyclic strain also significantly decreased upon initial aortic expansion and remained reduced, indicating the AAAs had stiffened vessel walls with initial aortic expansion. We are also exploring the heterogeneity of this AAA development using computational pulsatile flow models built from these ultrasound datasets. These models can provide information on site-specific changes in wall shear stress and oscillatory shear index, which are potentially predictive metrics for intramural thrombus formation and AAA growth.