基质金属蛋白酶3、9在升主动脉瘤中的表达

目的探讨基质金属蛋白酶3、9(MMP-3、MMP-9)在升主动脉瘤发病机制中的作用.方法将40只幼年Wistar大鼠随机分为对照组和实验组,制备升主动脉缩窄鼠模型.于术后3-5个月取升主动脉,采用HE染色和免疫组化技术,观察升主动脉形态学变化及MMP-3、MMP-9的蛋白表达.结果升主动脉瘤中MMP-3、MMP-9表达强阳性.结论 MMP-3、MMP-9在升主动脉瘤成因中有可能有重要作用.     

MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats

Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymographic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm.     

Long Telomeres in Blood Leukocytes Are Associated with a High Risk of Ascending Aortic Aneurysm

Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm.     

Aortic aneurysm in a Cebus apella monkey with experimentally induced atherosclerosis

The sudden death of a Cebus apella female (>19 years old) on an experimental hyperlipidic diet during three years is described. The gross lesions were hemothorax, atherosclerotic plaques in the aortic curve, and an aneurysm in the ascending aorta. Histologically, an enlargement of the intima in the ascending aorta with hyalinization and a thrombus were observed. The media was thinned and showed sclerosis and hemorrhage extending to the tunica adventicia.     

Measuring,reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries

Mice with a smooth muscle cell (SMC)-specific deletion of Fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourages the expression of contractile genes and prevents aneurysm development, but does not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta; therefore, mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment.     

Use of cardiopulmonary bypass, hypothermic perfusion, and circulatory arrest in the surgical management of basilar artery aneurysm

Two cases of intracranial aneurysm are discussed in relation to surgical management. The superiority of vena cavae/ascending aorta to femoral vein/femoral artery cannulation is indicated, thus minimizing ventricular fibrillation and myocardial damage.     

Blood flow patterns and pressure loss in the ascending aorta: A comparative study on physiological and aneurysmal conditions

An aortic aneurysm is defined as a balloon-shaped bulging of all three histologic components of the aortic vessel walls (intima, media and adventitia). This dilation results from vessel weakening owing to remodeling, i.e. due to cystic degeneration of the Tunica media (Marfan), progression of atherosclerosis or presence of a bicuspid aortic valve. The growth rate of the aortic diameter varies from patient to patient and may progress until the aneurysm ultimately ruptures. The role of hemodynamics, i.e. blood flow patterns, and shear stresses that are supposed to intensify during aneurysm growth are not yet fully understood, but thought to play a key role in the enlargement process. The aim of this study is to characterize the aortic blood flow in a silicone model of a pathological aorta with ascending aneurysm, to analyze the differences in the blood flow pattern compared to a healthy aortic model, and to single out possible blood flow characteristics measurable using phase contrast magnetic resonance imaging (MRI) that could serve as indicators for aneurysm severity. MRI simulations were performed under physiological, pulsatile flow conditions using data obtained from optical three dimensional particle tracking measurements. In comparison to the healthy geometry, elevated turbulence intensity and pressure loss are measured in the diseased aorta, which we propose as a complimentary indicator for assessing the aneurysmal severity. Our results shed a light on the interplay between the blood flow dynamics and their contribution to the pathophysiology and possible role for future risk assessment of ascending aortic aneurysms.     

Altered tissue behavior of a non-aneurysmal descending thoracic aorta in the mouse model of Marfan syndrome

Aortic aneurysm is predominantly found in the ascending aorta in patients with Marfan syndrome (MFS). However, descending aortic disease has emerged as a problem since people are living longer because of improved medical and surgical management of the ascending aorta. Diagnostic procedures before disease onset and the mechanisms involved in the transition of normal aortic tissue to aneurysm remain unclear. We determined signs of descending aortic disease before disease onset in mice with a mutation in the fibrillin 1 gene (Fbn1(+/C1039G)), a validated mouse model of disease susceptibility and progression of aortic aneurysm of MFS. We analyzed a tubular unfixed non-aneurysmal descending thoracic aorta from 8-month-old wild-type and Fbn1(+/C1039G) mice by a tubular biaxial tester that works in conjunction with a two-photon nonlinear microscope. Fbn1(+/C1039G) mouse aorta was more compliant in the circumferential direction. Two-photon imaging showed defective organization of adventitial collagen fibers in the pressurized aortas of Fbn1(+/C1039G) mice. Moreover, disruption in the elastic lamina was noted in the absence of aneurysms in pressurized aortas but not unpressurized aortas of Fbn1(+/C1039G) mice. At the molecular level, this altered tissue behavior in non-aneurysmal descending aortas of Fbn1(+/C1039G) mice was accompanied by an increasing trend of canonical but not noncanonical, transforming growth factor-β (TGFβ) signaling. Finally, assays of in vitro collagen lattice formation in mouse wild-type and TGFβ1-deficient embryonic fibroblasts indicate that TGFβ1 can regulate collagen organization. The ability to reveal the presence of altered biomechanics and microstructure coupled with subtle changes in TGFβ signaling provides a novel surrogate measure of tissue susceptibility to aneurysm before disease onset.     

COMBINED REPLACEMENT OF THE AORTIC VALVE AND ASCENDING AORTA IN JEHOVAH'S WITNESSES: REPORT OF TWO CASES

Two Jehovah's Witnesses with large ascending thoracic aortic aneurysms and aortic insufficiency secondary to annuloaortic ectasia underwent successful combined replacement of the aortic valve and the ascending aorta. One patient received a composite graft containing an aortic valve prosthesis, which necessitated supravalvular coronary ostia reimplantation; the other patient underwent separate aortic valve and left supracoronary ascending aneurysm replacement, with reimplantation of the right coronary ostium into the graft. No blood or blood derivatives were administered. Both patients had uneventful recoveries and continue to do well. To our knowledge, they represent the first reported cases of successful combined replacement of the aortic valve and ascending aorta in Jehovah's Witnesses.     

Aneurysm and Helicobacter pylori relationship: the seropositivity of CagA, VacA and other antigens of Helicobacter pylori in abdominal and ascending aortic aneurysms

Helicobacter pylori is thought to be related to atherosclerosis and aneurysm development. We aimed to detect virulance factors of H. pylori and examine the potential etiopathogenetic relationship between aortic aneurysm and H. pylori, 58 abdominal aortic aneurysm (AAA) and 38 ascending aortic aneurysm (AsAA) cases and 57 Healty control group (HCG) were included. We investigated H. pylori IgG by ELISA and virulance factors by Western-Blot (WB) method. No difference was found between AAA (67.24%), AsAA (73.68%) and HCG (57.89%) for H. pylori IgG (p > 0.05). A significant difference was found between AsAA (78.95%) and HCG (57.89%) for H.pylori IgG (p < 0.05) by ELISA and a significant difference was found only between AsAA (100%) and HCG (37.5%) for H. pylori IgG in the 45-55 age group by WB. A statistically significant difference was found between AAA and AsAA for VacA and CagA + VacA and CagA + VacA + UreA antigens and also a significant difference was found between AsAA and HCG for CagA + UreA antigens (p < 0.05). Finally, we suggest that H. pylori VacA has a more important role than CagA in the development of two aneurysms especially in ruptured AAA. New extended studies detecting H. pylori DNA are needed to detect the aetiopathogenesis between aneurysm types and H. pylori.     

Estimating aortic thoracic aneurysm rupture risk using tension–strain data in physiological pressure range: an in vitro study

Biomechanics and Modeling in Mechanobiology - Previous studies have shown that the rupture properties of an ascending thoracic aortic aneurysm (ATAA) are strongly correlated with the pre-rupture...     

Gender-Specific Differences in Outcome of Ascending Aortic Aneurysm Surgery

Objectives

Gender specific differences receive increasing attention and are known to affect the outcome of cardiovascular diseases. We investigated possible risk-factors for gender-specific differences in ascending aortic aneurysm surgery.

Methods

548 consecutive patients (male: n = 390, age: 58.3±14.4 years; female: n = 158, age: 65.3±12.9 years) with aneurysms of the ascending aorta eligible for cardiac surgery were retrospectively analyzed.

Results

Women were significantly older when operation was indicated (p<0.001) and presented with significantly more hypertension (p=0.04) and chronic obstructive pulmonary disease (COPD; p = 0.017), whereas men had significantly more previous cardiac operations (p = 0.016). Normalized aortic diameters (diameter / body surface area) were significantly larger in women (3.10±0.6 cm) vs. (2.75±0,5 cm, p≤0.001) in men, without differences in absolute values (5.74±1.04 cm vs. 5.86±1.34 cm). The aortic arch was significantly more involved in aneurysm formation in women (p = 0.04). Follow-up was available in 93% of the patients with a mean follow-up time of 3.9±3.9 (0-17.8) years. 30-day mortality was 3.5% in men (n=12) and 7.9% in women (n=11; p = 0.058). Univariate regression analysis shows gender specific risk factors for 30-day mortality in men to be age: p = 0.028; myocardial infarction: p = 0.0.24 and in women diameter of the ascending aorta: p=0.014; renal insufficiency: p=0.007. Long-term survival was significantly reduced in women (log-rank p = 0.0052).

Conclusions

The outcome after surgery for ascending aortic aneurysm is less favourable in women with significantly reduced long-term survival and a trend to increased 30-day mortality in this cohort. Larger normalized aortic diameters, higher incidence of involvement of the aortic arch and differences in comorbidities may contribute to gender differences. Women undergo surgery at higher age and more progressed state of aortic disease. Therefore, gender-specific guidelines for ascending replacement may be useful to improve outcome in women.     

Numerical simulation of saccular aneurysm hemodynamics: influence of morphology on rupture risk

The governing equations for pulsatile fluid flow were solved in their finite volume formulation in order to simulate blood flow in a variety of three-dimensional aneurysm geometries. The influence of geometric factors on flow patterns and fluid mechanical forces was studied with the goal of identifying the risk of aneurysm rupture. Aneurysm morphology was characterized by quantitative shape indices reflecting the three dimensionality of the vasculature derived from clinical studies. Recirculation zones and secondary flows were observed in aneurysms and arteries. Regions of extreme and alternating shear stress were observed and identified as sites for potential aneurysm rupture. The ellipticity of an aneurysm was observed to be strongly correlated with wall shear stress at the aneurysm fundus, while its non-sphericity, volume, and degree of undulation were more weakly correlated.     

Management of a right aberrant subclavian artery during complex hybrid stent-graft procedures: a rare and complex issue

A 76-year-old man with an ascending arch and proximal descending aortic aneurysm underwent a complex aortic replacement through a sternotomy with ligation of a right aberrant subclavian artery (RASA) distal to the right vertebral artery. The second-stage procedure was performed with a stent-graft deployed within the elephant trunk. At 6- and 12-month follow-up, the RASA was opacified by the patent right vertebral artery. Under ultrasound guidance, the patient's RASA stump was occluded by coils. Management of an RASA during complex hybrid stent-graft procedures is discussed.     

经胸超声胸骨右缘切面对Stanford A型主动脉夹层诊断价值的研究

目的:通过经胸超声心动图获取胸骨右缘升主动脉长短轴切面观察Stanford A型主动脉夹层患者的升主动脉结构,探讨对该类患者进行检查时该切面的应用价值。方法:31例经CTA或手术证实为A型主动脉夹层的连续性患者,超声心动图检查除常规通过胸骨左缘切面观察升主动脉结构外,均做胸骨右缘切面以进一步观察升主动脉结构,包括最大内径,有无撕脱内膜及内膜活动情况,同时应用常规胸骨左缘切面和胸骨右缘切面对A型主动脉夹层能够清晰显示出的病例比例加以比较。结果:胸骨左缘切面能够清晰显示升主动脉结构9例,占比例29%。胸骨右缘切面能够清晰显示升主动脉结构20例,比例65%。将两种切面结合能够清晰显示升主动脉结构的比例升高到74%。胸骨右缘肋间切面测得的升主动脉最大径线数值与CTA结果的一致性更好。结论:胸骨右缘肋间切面对A型主动脉夹层显示的清晰度更好,有助于临床诊断,具有重要的参考价值,值得临床广泛推广。     

Mycotic aortic aneurysm complicating isolated partial anomalous pulmonary venous drainage

An aneurysm that develops within a normal segment of the ascending aorta in a child with asymptomatic and previously undiagnosed congenital heart disease at the atrial level is most unusual and highly lethal. This report describes a child who had successful corrective surgery for this anomaly.     

ASCENDING AORTIC ANEURYSM RESECTION EIGHT MONTHS AFTER TRIPLE CORONARY ARTERY BYPASS: CASE REPORT

This report involves the surgical treatment of a patient who underwent saphenous vein triple coronary artery bypass and subsequently developed an ascending aortic aneurysm and aortic insufficiency. Although the implantation of vascular structures into synthetic grafts is commonplace, this case is unique in that it involves the successful implantation of an aortic island containing the origin of the coronary arteries.     

Hemodynamics of the mouse abdominal aortic aneurysm

The abdominal aortic aneurysm (AAA) is a significant cause of death and disability in the Western world and is the subject of many clinical and pathological studies. One of the most commonly used surrogates of the human AAA is the angiotensin II (Ang II) induced model used in mice. Despite the widespread use of this model, there is a lack of knowledge concerning its hemodynamics; this study was motivated by the desire to understand the fluid dynamic environment of the mouse AAA. Numerical simulations were performed using three subject-specific mouse models in flow conditions typical of the mouse. The numerical results from one model showed a shed vortex that correlated with measurements observed in vivo by Doppler ultrasound. The other models had smaller aneurysmal volumes and did not show vortex shedding, although a recirculation zone was formed in the aneurysm, in which a vortex could be observed, that elongated and remained attached to the wall throughout the systolic portion of the cardiac cycle. To link the hemodynamics with aneurysm progression, the remodeling that occurred between week one and week two of the Ang II infusion was quantified and compared with the hemodynamic wall parameters. The strongest correlation was found between the remodeled distance and the oscillatory shear index, which had a correlation coefficient greater than 0.7 for all three models. These results demonstrate that the hemodynamics of the mouse AAA are driven by a strong shear layer, which causes the formation of a recirculation zone in the aneurysm cavity during the systolic portion of the cardiac waveform. The recirculation zone results in areas of quiescent flow, which are correlated with the locations of the aneurysm remodeling.     

TGF-β Neutralization Enhances AngII-Induced Aortic Rupture and Aneurysm in Both Thoracic and Abdominal Regions

AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have attenuated the neutralization. In contrast, a mouse TGF-β antibody (1D11) significantly increased rupture in both the ascending and suprarenal aortic regions, but only at doses that markedly decreased serum TGF-β concentrations. High doses of 1D11 antibody significantly increased AngII-induced ascending and suprarenal aortic dilatation. To determine whether TGF-β neutralization had effects in mice previously infused with AngII, the 1D11 antibody was injected into mice that had been infused with AngII for 28 days and were observed during continued infusion for a further 28 days. Despite near ablations of serum TGF-β concentrations, the mouse TGF-β antibody had no effect on aortic rupture or dimensions in either ascending or suprarenal region. These data provide further evidence that AngII-induced aortic rupture is enhanced greatly by TGF-β neutralization when initiated before pathogenesis.     

Comparison of bacterial diversity along the human intestinal tract by direct cloning and sequencing of 16S rRNA genes

Bacterial diversity of the mucosal biopsies from human jejunum, distal ileum, ascending colon and rectum were compared by analysis of PCR-amplified 16S rDNA clone libraries. A total of 347 clones from the mucosal biopsies were partially sequenced and assigned to six phylogenetic phyla of the domain Bacteria: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Verrucomicrobia, and Actinobacteria. The jejunum sample had least microbial diversity compared to the other samples and a trend towards highest diversity in ascending colon was observed. The clone libraries of distal ileum, ascending colon and rectum were not significantly different from each other (P>0.0043), but they differed significantly from the jejunum library (P=0.001). The population of sequences retrieved from jejunal biopsies was dominated by sequences closely related to Streptococcus (67%), while the population of sequences derived from distal ileum, ascending colon and rectum were dominated by sequences affiliated with Bacteroidetes (27-49%), and Clostridium clusters XIVa (20-34%) and IV (7-13%). The results indicate that the microbial community in jejunum is different from those in distal ileum, ascending colon and rectum, and that the major phylogenetic groups are similar from distal ileum to rectum.