Effect of Variation in Intraluminal Thrombus Constitutive Properties on Abdominal Aortic Aneurysm Wall Stress

The abdominal aortic aneurysm (AAA) is a degenerating disease for which the end stage is the rupture of the vessel wall. Accurate prediction of the stresses acting on the aneurysm tissue may be used to determine the actual risk of rupture of a specific aneurysm. To accomplish this, a correct constitutive model for the aneurysmal aortic wall and any intraluminal thrombus (ILT) present within it are needed. Our laboratory has previously reported the mechanical properties of ILT. The aim of this work is to investigate the reliability of using population-mean values of ILT constitutive parameters to estimate AAA wall stress distribution. For this, a three-dimensional asymmetric model of an aneurysm including ILT was generated and a parametric study was conducted varying ILT constitutive properties within a physiological range. Results show that the presence of any ILT reduces and redistributes the stresses in the aortic wall markedly. Maximum variation in the peak wall stresses for all the models analyzed was 5%. Adopting a nonhomogeneous ILT did not alter the stress distribution. On the basis of these results, we infer that population mean parameters for ILT material characteristics can be used to reasonably estimate the wall stresses in patient specific aneurysm models. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8710+e     

Phosphorylation of AKT and Abdominal Aortic Aneurysm Formation

It is hypothesized that differential AKT phosphorylation between sexes is important in abdominal aortic aneurysm (AAA) formation. Male C57BL/6 mice undergoing elastase treatment showed a typical AAA phenotype (80% over baseline, P < 0.001) and significantly increased phosphorylated AKT-308 (p308) and total-AKT (T-AKT) at day 14 compared with female mice. Elastase-treated Raw cells produced increased p308 and significant amounts of matrix metalloproteinase 9 (MMP-9), and these effects were suppressed by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 treatment, a known AKT inhibitor. Male and female rat aortic smooth muscle cells treated with elastase for 1, 6, or 24 hours demonstrated that the p308/T-AKT and AKT-Ser-473/T-AKT ratios peaked at 6 hours and were significantly higher in the elastase-treated cells compared with controls. Similarly, male cells had higher phosphorylated AKT/T-AKT levels than female cells. {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 also inhibited elastase-induced p308 formation more in female smooth muscle cells than in males, and the corresponding cell media had less pro–MMP-9. AKT siRNA significantly decreased secretion of pro–MMP-9, as well as pro–MMP-2 and active MMP-2 from elastase-treated male rat aortic smooth muscle cells. IHC of male mice AAA aortas showed increased p308, AKT-Ser-473, and T-AKT compared with female mice. Aortas from male AAA patients had a significantly higher p308/T-AKT ratio than female AAA tissues. These data suggest that AKT phosphorylation is important in the upstream regulation of MMP activity, and that differential phosphorylation may be important in sex differences in AAA.Abdominal aortic aneurysm (AAA) formation is accompanied by chronic inflammation of the aorta wall, with males four times more likely to develop the disease than females.¹ The activation of matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, has long been known to play a vital role in the destruction of the aortic wall, leading to AAA development.^2–6 However, little is known about upstream modulation of the MMPs during AAA formation. Activation of the molecules of the mitogen-activated protein (MAP) kinase pathways is often observed in inflammatory diseases, such as in AAAs. Two MAP kinases in particular, c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinase (ERK), have been shown to be important in the activation of MMP-2 and MMP-9 in the aorta.^7–10 In addition to the MAP kinase cascade, the molecules of the phosphoinositide 3-kinase pathway are also known to be important for the modulation of MMPs.^9,11–15 Moreover, AKT, a key molecule in the phosphoinositide 3-kinase pathway, has been shown to play an important role in sex-specific differences of various diseases.^16–20 The role of AKT in the modulation of MMPs has not been studied in AAA formation. Therefore, using an in vivo mouse model of AAA and human AAA tissue, as well as in vitro experiments with rat aortic smooth muscle cells (RASMCs) and Raw cells, we show increased phosphorylation of AKT in males compared with females.     

The Novel Association of the Chemokine CCL22 with Abdominal Aortic Aneurysm

The aim of this study was to examine aortic biopsies with a cytokine array to identify new cytokines associated with abdominal aortic aneurysm (AAA). We assessed the relative expression of 79 cytokines using antibody-based cytokine arrays in a total of 12 AAA and 12 control aortic biopsies. Based on these findings we validated the findings for one cytokine by examining a further 11 AAA and 11 atherothrombosis biopsies and serum from 1028 men, 315 of whom had an AAA. Three cytokines (interleukins 1B and 8, and Chemokine CC motif ligand 22 [CCL22]) were consistently up-regulated in AAA biopsies. Since CCL22 had not previously been associated with aortic dilatation, we confirmed the upregulation of this cytokine in further tissue biopsies and serum using enzyme-linked immunosorbent assay. Median serum concentrations of CCL22 were greater in men with AAA (0.69 ng/ml) than controls (0.56 ng/ml, P < 0.01). Serum CCL22 was independently associated with both small (OR 1.51, 95% CI 1.21–1.88) and large AAA (OR 1.33, 95% CI 1.08–1.62) after adjusting for other risk factors. The association between CCL22 and AAA was also confirmed using immunohistochemistry. The results presented in this study demonstrate a novel association between CCL22 and AAA as well as illustrate how a protein array can be used to identify novel markers of potential pathogenic and diagnostic significance for AAA.Abdominal aortic aneurysm (AAA) is recognized as an important cause of mortality.¹ Marked accumulation of leukocytes, macrophages, B and T cells is a consistent finding in biopsies of human AAA.^2,3 The influx, migration, and effects of these cells are controlled by an array of pro-inflammatory cytokines, chemokines, and growth factors (referred to collectively as cytokines in this article).^4,5 High concentrations of various cytokines have been demonstrated in both AAA biopsies and within the circulation of patients with AAA.^6,7,8 Some cytokines, such as interleukin (IL) 6, have been shown to be present within the circulation at increased concentrations distal to AAAs, suggesting they are released directly from the aortic wall.⁸ At present, however, which cytokines are most relevant to AAA is not clear.We hypothesized that cytokines up-regulated within human AAA biopsies would also be present in increased concentrations within the circulation of patients. The aim of this study was to identify cytokines consistently up-regulated within human AAA biopsies using antibody arrays to measure relative expression of 79 proteins. The up-regulation of one cytokine in human AAA, not previously associated with aortic dilatation, was validated in additional aortic biopsies using alternative outcome techniques and further examined within the blood of 1028 men to assess any association between circulating levels and AAA.     

A Comparison of Diameter,Wall Stress,and Rupture Potential Index for Abdominal Aortic Aneurysm Rupture Risk Prediction

An abdominal aortic aneurysm (AAA) is a balloon-like dilation of the aorta, which is potentially fatal in case of rupture. Computational finite element (FE) analysis is a promising approach to a more accurate and patient-specific rupture risk prediction. AAA wall strength and rupture potential index (RPI) calculation are implemented in our FE software. Static structural FE simulations are performed on n = 30 non-ruptured asymptomatic, n = 9 non-ruptured symptomatic, and n = 14 ruptured AAAs. We calculate maximum values for diameter, wall displacement, strain, stress, and RPI as well as minimum wall strength for every AAA. All investigated quantities, except minimum strength, show statistically significant differences between non-ruptured asymptomatic and symptomatic/ruptured AAAs. Maximum wall stress and especially the RPI are notably increased for symptomatic and ruptured AAAs. The biggest difference is found to be the RPI (Δ = 44.9%, p = 8.0e−5). Lowest RPI obtained for symptomatic or ruptured AAAs is 0.3. The RPI of more than 55% of the investigated asymptomatic AAAs falls below this value. Maximum wall stress and maximum RPI criteria enable a reliable rupture risk evaluation for AAAs. Especially in the diameter range where surgical indication is not obvious, the RPI holds great potential for improvement of clinical decisions.     

腹主动脉瘤应力模型的建立及其应用

本研究用螺旋CT扫描腹主动脉瘤获得的断层图像合成腹主动脉瘤几何模型，通过设定瘤壁组织生物力学参数和边界条件，使用有限元分析的方法分析腹主动脉瘤瘤壁的应力分布。结果标明，本例腹主动脉瘤应力峰值位于远端分叉部位，瘤体应力峰值位于后壁，均小于瘤壁的承受极限。本研究所得结果对腹主动脉瘤应力模型有助于分析个体化腹主动脉瘤的破裂部位和生长方向，对研究疾病进程提供依据。     

The Role of Geometric and Biomechanical Factors in Abdominal Aortic Aneurysm Rupture Risk Assessment

The current clinical management of abdominal aortic aneurysm (AAA) disease is based to a great extent on measuring the aneurysm maximum diameter to decide when timely intervention is required. Decades of clinical evidence show that aneurysm diameter is positively associated with the risk of rupture, but other parameters may also play a role in causing or predisposing the AAA to rupture. Geometric factors such as vessel tortuosity, intraluminal thrombus volume, and wall surface area are implicated in the differentiation of ruptured and unruptured AAAs. Biomechanical factors identified by means of computational modeling techniques, such as peak wall stress, have been positively correlated with rupture risk with a higher accuracy and sensitivity than maximum diameter alone. The objective of this review is to examine these factors, which are found to influence AAA disease progression, clinical management and rupture potential, as well as to highlight on-going research by our group in aneurysm modeling and rupture risk assessment.     

Evaluation of Texture for Classification of Abdominal Aortic Aneurysm After Endovascular Repair

The use of the endovascular prostheses in abdominal aortic aneurysm has proven to be an effective technique to reduce the pressure and rupture risk of aneurysm. Nevertheless, in a long-term perspective, complications such as leaks inside the aneurysm sac (endoleaks) could appear causing a pressure elevation and increasing the danger of rupture consequently. At present, computed tomographic angiography (CTA) is the most common examination for medical surveillance. However, endoleak complications cannot always be detected by visual inspection on CTA scans. The investigation on new techniques to detect endoleaks and analyse their effects on treatment evolution is of great importance for endovascular aneurysm repair (EVAR) technique. The purpose of this work was to evaluate the capability of texture features obtained from the aneurysmatic thrombus CT images to discriminate different types of evolutions caused by endoleaks. The regions of interest (ROIs) from patients with different post-EVAR evolution were extracted by experienced radiologists. Three techniques were applied to each ROI to obtain texture parameters, namely the grey level co-occurrence matrix (GLCM), the grey level run length matrix (GLRLM) and the grey level difference method (GLDM). The results showed that GLCM, GLRLM and GLDM features presented a good discrimination ability to differentiate between favourable or unfavourable evolutions. GLCM was the most efficient in terms of classification accuracy (93.41% ± 0.024) followed by GLRLM (90.17% ± 0.077) and finally by GLDM (81.98% ± 0.045). According to the results, we can consider texture analysis as complementary information to classified abdominal aneurysm evolution after EVAR.     

Chemical Mediators of Inflammation and Resolution in Post-Operative Abdominal Aortic Aneurysm Patients

Temporal–metabolomic studies of local mediators during inflammation and its resolution uncovered novel pathways and mediators, e.g., lipoxins, resolvins, and protectins that stimulate key resolution responses. Since these studies were carried out with isolated human cells and in animal models, it is important to determine in humans whether temporal profiles between pro-inflammatory mediators and pro-resolving mediators are demonstrable in vivo. To this end, we examined patients undergoing abdominal aortic aneurysm (AAA) surgery. Profiles of mediators including eicosanoids were assessed in addition to pro-resolving mediators. The results demonstrate temporal relationships for local-acting peptides (e.g., VEGF, IL-10, TGF_β) and lipid mediators (leukotrienes and resolvins). In addition, profiles obtained for AAA patients divided into two groups based on their temporal profile: one group consistent with a pro-inflammatory and another with a resolving profile. Together, these translational metabolomic profiles demonstrate for the first time the temporal relationships between local mediators in humans relevant in inflammation resolution.     

A Framework for the Automatic Generation of Surface Topologies for Abdominal Aortic Aneurysm Models

Patient-specific abdominal aortic aneurysms (AAAs) are characterized by local curvature changes, which we assess using a feature-based approach on topologies representative of the AAA outer wall surface. The application of image segmentation methods yields 3D reconstructed surface polygons that contain low-quality elements, unrealistic sharp corners, and surface irregularities. To optimize the quality of the surface topology, an iterative algorithm was developed to perform interpolation of the AAA geometry, topology refinement, and smoothing. Triangular surface topologies are generated based on a Delaunay triangulation algorithm, which is adapted for AAA segmented masks. The boundary of the AAA wall is represented using a signed distance function prior to triangulation. The irregularities on the surface are minimized by an interpolation scheme and the initial coarse triangulation is refined by forcing nodes into equilibrium positions. A surface smoothing algorithm based on a low-pass filter is applied to remove sharp corners. The optimal number of iterations needed for polygon refinement and smoothing is determined by imposing a minimum average element quality index with no significant AAA sac volume change. This framework automatically generates high-quality triangular surface topologies that can be used to characterize local curvature changes of the AAA wall.     

腹主动脉瘤切除-人造血管置换术的麻醉管理

目的 总结腹主动脉瘤切除术及人造血管置换术的麻醉管理.方法 回顾20例腹主动脉瘤切除术及人造血管置换术的麻醉处理过程,对输液量、术中并发症、血压及心率等重要指标进行分析整理.结果 在主动脉阻断和开放时血流动力学波动比较剧烈,经处理后循环功能维持稳定,肾功能在术中未受到明显影响.所有患者都安全地度过了手术,无患者在术中发生死亡.结论 完善的麻醉监测、及时纠正代谢紊乱和维持循环稳定是患者安全度过围术期的有效保证.     

Detection of Chlamydia pneumoniae DNA in Buffy-Coat Samples of Patients with Abdominal Aortic Aneurysm

 Recent studies have suggested that Chlamydia pneumoniae infection is a risk factor for abdominal aortic aneurysm. This study explores the presence of Chlamydia pneumoniae DNA in buffy-coat samples of control subjects and of patients with abdominal aortic aneurysm. The seroepidemiological association between abdominal aortic aneurysm and Chlamydia pneumoniae was also investigated. Buffy-coat samples and serum specimens were obtained from 88 patients and 88 control subjects. Detection of Chlamydia pneumoniae DNA in buffy-coat samples and measurement of IgG antibodies to Chlamydia pneumoniae in serum specimens were performed by polymerase chain reaction and microimmunofluorescence, respectively. Chlamydia pneumoniae DNA was detected in buffy-coat samples of 18 (20%) patients and 8 (9%) control subjects (adjusted odds ratio 2.9, 95% confidence interval 1–8.5). IgG antibodies to Chlamydia pneumoniae were detected in 85 (97%) patients and 71 (81%) control subjects (adjusted odds ratio 7.2, 95% confidence interval 1.7–31). The results show an association between abdominal aortic aneurysm and either the presence of Chlamydia pneumoniae DNA in buffy-coat samples or IgG antibodies to Chlamydia pneumoniae. These findings support the hypothesis that previous infection with Chlamydia pneumoniae might be a risk factor for abdominal aortic aneurysm.     

稳恒流下腹主动脉旁瘤超声多普勒血流信号的仿真分析

腹主动脉旁瘤超声多普勒血流信号的仿真研究,可以为采用超声多普勒技术检测腹主动脉旁瘤的形成、生长过程和估计动脉旁瘤瘤体大小提供指导.先通过有限元数值计算方法得到稳恒流下腹主动脉旁瘤区域内的血液流场分布,然后采用余弦叠加的合成方法仿真出相应的超声多普勒血流信号.最后对仿真信号进行频谱分析,计算其平均频率,并研究它与腹主动脉旁瘤瘤体大小的关系.结果 表明:当动脉旁瘤较小时,平均频率的幅度变化较小;当动脉旁瘤较大时,平均频率的幅度变化较大.因此,采用平均频率的幅度变化可以在一定程度上估计动脉旁瘤的瘤体大小.     

瘤颈角度对腹主动脉瘤腔内修复术后支架位移的影响

目的 研究瘤颈角度对腹主动脉瘤腔内修复术后支架位移的影响。方法 选用28名患者CT影像分别建立术前腹主动脉瘤(abdominal aortic aneurysm, AAA)模型、术后两次随访(postoperative follow-up)AAA模型和覆膜支架模型,并根据术前瘤颈角度将模型分为非严重成角组(n=14)和严重成角组(n=14)。测量每个模型的几何形态,分析手术前后AAA几何参数、术后支架位移变化。通过血流动力学模拟计算术后第1次随访模型的位移力。结果 两组患者在瘤长度、最大直径、位移力、瘤颈长度变化和瘤体积变化有明显差异(P<0.05)。支架重心位移和近端位移无显著差异(P>0.05)。在内漏发生情况上,未严重成角组中有2例,严重成角组中有4例(P>0.05)。结论 严重的瘤颈成角可导致支架位移力显著增加以及近端锚固区减小,进而增加支架位移发生的可能性。建议在临床方面医生应加强对严重瘤颈成角患者的术后随访,警惕远期内漏的发生。     

A Systematic Review of Studies Examining Inflammation Associated Cytokines in Human Abdominal Aortic Aneurysm Samples

Objectives: Inflammation is critical in abdominal aortic aneurysm (AAA) but there is no current consensus on which inflammation related cytokines are important. The aim of this review was to systemically assess previous studies investigating the relative expression of inflammation associated cytokines within human AAA samples. Methods: The MEDLINE database was searched for studies which simultaneously examined an array of different inflammation associated cytokines in aortic samples in order to identify those associated with AAA. Focused searches were then conducted for further studies assessing relative concentrations of these cytokines in aortic samples in relation to AAA. Appropriate studies were assessed by two reviewers independently. Results: Eighteen studies were included. A number of different cytokines have been consistently found to be upregulated within AAA by comparison to aortic samples removed from patients without cardiovascular disease, however findings relative to samples of aortic athero-thrombosis were less consistent. TNFA and INFG appear to be the most consistently associated with AAA in studies using both normal and atherosclerotic controls. Cautious interpretation of these data is recommended due to a number of methodological problems. Conclusions: This systematic review suggests that TNFA and INFG are the most consistently upregulated cytokines in large AAAs. Further studies utilizing larger populations, new proteomic techniques and better patient matching are required.     

腹主动脉缩窄法致大鼠心肌纤维化模型的建立

目的用腹主动脉缩窄法建立大鼠心肌纤维化模型。方法16只雄性SD大鼠随机分为腹主动脉缩窄组（模型组）及假手术组。分别比较两组左室心肌质量指数、左室心肌病理形态HE染色及左室心肌胶原染色等指标造模4周及造模8周时的变化。结果模型组造模4周及8周时左室重量指数（LVMI）较假手术组显著升高（P〈0.05）。胶原染色、HE染色及超微结构等病理变化,模型组造模4周、8周较假手术组改变明显;假手术组4周及8周时基本一致。结论SD大鼠在腹主动脉缩窄术后4周即可达心肌纤维化模型。