Novel biaxial tensile test for studying aortic failure phenomena at a microscopic level

Background

An aortic aneurysm is a local dilation of the aorta, which tends to expand and often results in a fatal rupture. Although larger aneurysms have a greater risk of rupture, some small aneurysms also rupture. Since the mechanism of aortic rupture is not well understood, clarification of the microstructure influencing the failure to rupture is important. Since aortic tissues are stretched biaxially in vivo, we developed a technique to microscopically observe the failure of an aortic rupture during biaxial stretch.

Methods

A thinly sliced porcine thoracic aortic specimen was adhered to a circular frame and pushed onto a cylinder with a smaller diameter to stretch the specimen biaxially. To induce failure to rupture at the center, the specimen was thinned at the center of the hole as follows: the specimen was frozen while being compressed with metal plates having holes, which were 3 mm in diameter at their centers; the specimen was then sliced at 50-μm intervals and thawed.

Results

The ratio of the thickness at the center to the peripheral area was 99.5% for uncompressed specimens. The ratio decreased with an increase in the compression ratio ε _c and was 47.3% for specimens with ε _c = 40%. All specimens could be stretched until failure to rupture. The probability for crack initiation within the cylinder was <30% and 100% for specimens with ε _c <10% and ε _c >30%, respectively. Among specimens ruptured within the cylinder, 93% of those obtained from the mid-media showed crack initiation at the thin center area.

Conclusions

Aortic tissues were successfully stretched biaxially until failure, and their crack initiation points were successfully observed under a microscope. This could be a very useful and powerful method for clarifying the mechanism of aortic rupture. We are planning to use this technique for a detailed investigation of events occurring at the point of failure when the crack initiates in the aortic aneurysm wall.     

Aortic dissection in a gorilla

Autopsy findings in a 39-year-old male gorilla included aortic dissection, internal rupture of the aortic arch with axial direction of the tear, external rupture of the ascending aorta, cardiac tamponade, myocardial hypertrophy, cystic and basophilic degeneration of the aortic media, marked obesity, severe degenerative joint disease, focal glomerulonephritis, and widespread hemosiderosis.     

Role of spiral computed tomographic angiography in the diagnosis of aortic aneurysmal complications

The paper considers the basic diagnostic capacities of computed tomographic angiography (CTA) in aortic aneurysmal complications. The results of emergency of CTA were analyzed In 63 patients with suspected aortic aneurysmal dissection and rupture. CTA provides complete information on the site, extent, and spread, form and sizes of an aneurismal process, on the presence of intraluminal thrombi, on the presence or absence of aortic wall dissection and rupture, on the involvement of aortic branches, and the state of adjacent tissues and organs.     

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.     

Biomechanics of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a condition whereby the terminal aorta permanently dilates to dangerous proportions, risking rupture. The biomechanics of AAA has been studied with great interest since aneurysm rupture is a mechanical failure of the degenerated aortic wall and is a significant cause of death in developed countries. In this review article, the importance of considering the biomechanics of AAA is discussed, and then the history and the state-of-the-art of this field is reviewed--including investigations into the biomechanical behavior of AAA tissues, modeling AAA wall stress and factors which influence it, and the potential clinical utility of these estimates in predicting AAA rupture.     

THE VALUE OF ECHOCARDIOGRAPHY IN THE MANAGEMENT OF ACUTE AORTIC INSUFFICIENCY

Three cases of acute rupture of the aortic cusp complicating bacterial endocarditis are described. Special emphasis is placed on the value of serial echocardiography as a means of identifying progressive changes in aortic valve anatomy during the destructive process of the disease. Prior to the results of blood cultures, an echocardiogram confirmed a diagnosis of vegetations on the valve cusps. It also demonstrated flailing of the aortic cusp, which was confirmed at operation. Echocardiographic findings of flailing aortic valves in these patients coincided with the onset of acute aortic insufficiency and contributed to the timing of surgical intervention for replacement of the affected valves.     

Mechano-biology in the thoracic aortic aneurysm: a review and case study

An aortic aneurysm is a permanent and localized dilatation of the aorta resulting from an irreversible loss of structural integrity of the aortic wall. The infrarenal segment of the abdominal aorta is the most common site of aneurysms; however, they are also common in the ascending and descending thoracic aorta. Many cases remain undetected because thoracic aortic aneurysms (TAAs) are usually asymptomatic until complications such as aortic dissection or rupture occurs. Clinical estimates of rupture potential and dissection risk, and thus interventional planning for TAAs, are currently based primarily on the maximum diameter and growth rate. The growth rate is calculated from maximum diameter measurements at two subsequent time points; however, this measure cannot reflect the complex changes of vessel wall morphology and local areas of weakening that underline the strong regional heterogeneity of TAA. Due to the high risks associated with both open and endovascular repair, an intervention is only justified if the risk for aortic rupture or dissection exceeds the interventional risks. Consequently, TAAs clinical management remains a challenge, and new methods are needed to better identify patients for elective repair. We reviewed the pathophysiology of TAAs and the role of mechanical stresses and mathematical growth models in TAA management; as a proof of concept, we applied a multiscale biomechanical analysis to a case study of TAA.     

3D geometric reconstruction of thoracic aortic aneurysms

Background  

The thoracic aortic aneurysm (TAA) is a pathology that involves an expansion of the aortic diameter in the thoracic aorta, leading to risk of rupture. Recent studies have suggested that internal wall stress, which is affected by TAA geometry and the presence or absence of thrombus, is a more reliable predictor of rupture than the maximum diameter, the current clinical criterion. Accurate reconstruction of TAA geometry is a crucial step in patient-specific stress calculations.     

Marfan syndrome with coronary artery lesions in a North American Indian.

Marfan syndrome has not been well documented in North American Indians. A 19-year old Ojibwa man had evidence of this syndrome -- specifically, tall stature, long, thin extremities (particularly, fingers and toes), increased urinary excretion of hydroxyproline, aortic aneurysm, aortic regurgitation and pathologic evidence of aortic rupture and alastic tissue fragmentation. Intimal hyperplasia was present in the extramural coronary arteries, while the intramural arteries, usually thought to be involved, were normal.     

Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models

Background  

Abdominal aortic aneurysm (AAA) is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs.     

Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome

Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. We investigated the structural and functional properties of the heart and aorta in a [Fbn1^C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was performed on 12-month old WT and MFS fixed mouse hearts to measure ventricular volume and mass. The PWV was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWV increased with age in MFS mice only. We also found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared with WT for both age groups. The [Fbn1^C1039G/+] mouse model of MFS replicates many of the anomalies of Marfan patients including significant aortic dilation, central aortic stiffness, LV systolic and diastolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.     

Automated methodology for determination of stress distribution in human abdominal aortic aneurysm

Knowledge of impending abdominal aortic aneurysm (AAA) rupture can help in surgical planning. Typically, aneurysm diameter is used as the indicator of rupture, but recent studies have hypothesized that pressure-induced biomechanical stress may be a better predictor Verification of this hypothesis on a large study population with ruptured and unruptured AAA is vital if stress is to be reliably used as a clinical prognosticator for AAA rupture risk. We have developed an automated algorithm to calculate the peak stress in patient-specific AAA models. The algorithm contains a mesh refinement module, finite element analysis module, and a postprocessing visualization module. Several aspects of the methodology used are an improvement over past reported approaches. The entire analysis may be run from a single command and is completed in less than 1 h with the peak wall stress recorded for statistical analysis. We have used our algorithm for stress analysis of numerous ruptured and unruptured AAA models and report some of our results here. By current estimates, peak stress in the aortic wall appears to be a better predictor of rupture than AAA diameter. Further use of our algorithm is ongoing on larger study populations to convincingly verify these findings.     

Cyclooxygenase-2 Inhibition Attenuates Abdominal Aortic Aneurysm Progression in Hyperlipidemic Mice

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory disease that increase the risk of life-threatening aortic rupture. In humans, AAAs have been characterized by increased expression of cyclooxygenase-2 and the inactivation of COX-2 prior to disease initiation reduces AAA incidence in a mouse model of the disease. The current study examined the effectiveness of selective cyclooxygenase-2 (COX-2) inhibition on reducing AAA progression when administered after the initiation of AAA formation. AAAs were induced in hyperlipidemic apolipoprotein E-deficient mice by chronic angiotensin II (AngII) infusion and the effect of treatment with the COX-2 inhibitor celecoxib was examined when initiated at different stages of the disease. Celecoxib treatment that was started 1 week after initiating AngII infusion reduced AAA incidence by 61% and significantly decreased AAA severity. Mice treated with celecoxib also showed significantly reduced aortic rupture and mortality. Treatment with celecoxib that was started at a late stage of AAA development also significantly reduced AAA incidence and severity. Celecoxib treatment significantly increased smooth muscle alpha-actin expression in the abdominal aorta and did not reduce expression of markers of macrophage-dependent inflammation. These findings indicate that COX-2 inhibitor treatment initiated after formation of AngII-induced AAAs effectively reduces progression of the disease in hyperlipidemic mice.     

A decoupled fluid structure approach for estimating wall stress in abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is a localized dilatation of the aortic wall. The lack of an accurate AAA rupture risk index remains an important problem in the clinical management of the disease. To accurately estimate AAA rupture risk, detailed information on patient-specific wall stress distribution and aortic wall tissue yield stress is required. A complete fluid structure interaction (FSI) study is currently impractical and thus of limited clinical value. On the other hand, isolated static structural stress analysis based on a uniform wall loading is a widely used approach for AAA rupture risk estimation that, however, neglects the flow-induced wall stress variation. The aim of this study was to assess the merit of a decoupled fluid structure analysis of AAA wall stress. Anatomically correct, patient specific AAA wall models were created by 3D reconstruction of computed tomography images. Flow simulations were carried out with inflow and outflow boundary conditions obtained from patient extracted data. Static structural stress analysis was performed applying both a uniform pressure wall loading and a flow induced non-uniform pressure distribution obtained during early systolic deceleration. For the structural analysis, a hyperelastic arterial wall model and an elastic intraluminal thrombus model were assumed. The results of this study demonstrate that although the isolated static structural stress analysis approach captures the gross features of the stress distribution it underestimates the magnitude of the peak wall stress by as much as 12.5% compared to the proposed decoupled fluid structure approach. Furthermore, the decoupled approach provides potentially useful information on the nature of the aneurysmal sac flow.     

In vitro analysis of localized aneurysm rupture

In this study, bulge inflation tests were used to characterize the failure response of 15 layers of human ascending thoracic aortic aneurysms (ATAA). Full field displacement data were collected during each of the mechanical tests using a digital image stereo-correlation (DIS-C) system. Using the collected displacement data, the local stress fields at burst were derived and the thickness evolution was estimated during the inflation tests. It was shown that rupture of the ATAA does not systematically occur at the location of maximum stress, but in a weakened zone of the tissue where the measured fields show strain localization and localized thinning of the wall. Our results are the first to show the existence of weakened zones in the aneurysmal tissue when rupture is imminent. An understanding these local rupture mechanics is necessary to improve clinical assessments of aneurysm rupture risk. Further studies must be performed to determine if these weakened zones can be detected in vivo using non-invasive techniques.     

Biomechanical Characterization of Ascending Aortic Aneurysms

Biomechanics and Modeling in Mechanobiology - Ascending thoracic aortic aneurysms (ATAAs) are a silent disease, ultimately leading to dissection or rupture of the arterial wall. There is a growing...     

Ruptured Abdominal Aortic Aneurysms: Surgical Treatment

The records of 62 consecutive patients with ruptured abdominal aortic aneurysms were analyzed to determine what factors contribute to lower mortality. Survival was directly related to the immediate preoperative hemodynamic status of the patients. In 18 cases in which operation was carried out with patients stable, 83 percent of the patients survived. Even if shock was present by the time of operation (37 cases), a 68 percent survival rate was achieved. Cardiac arrest occurred before obtaining aortic control in seven patients and one survived.Survival rates were increased if certain preoperative, operative and postoperative guidelines were followed. Since the combined operative mortality and late graft failure rate in 125 elective aneurysmectomies done during the same decade was under 5 percent, all abdominal aortic aneurysms with few exceptions should be surgically treated before rupture occurs.     

A tool and an instrument modification to facilitate aortic flow probe placement

A tool was designed and fabricated to simplify the procedure of placing a flow probe around the aortic root in acute animal experiments. The tool was made from a section of silicone rubber tubing which was flattened and tapered at one end. The flow probe was inserted into the open end of the tool, and the tapered end was drawn under the aorta, thus pulling the probe into position. Grooves were also ground into the probe body to ease the installation of the slot cover. During the 2 years that the tool and modified probes were used, they saved time and eliminated rupture of vessels as complications of aortic root flow probe placement.     

Modeling of the aorta artery aneurysms and renal artery stenosis using cardiovascular electronic system

Background  

The aortic aneurysm is a dilatation of the aortic wall which occurs in the saccular and fusiform types. The aortic aneurysms can rupture, if left untreated. The renal stenosis occurs when the flow of blood from the arteries leading to the kidneys is constricted by atherosclerotic plaque. This narrowing may lead to the renal failure. Previous works have shown that, modelling is a useful tool for understanding of cardiovascular system functioning and pathophysiology of the system. The present study is concerned with the modelling of aortic aneurysms and renal artery stenosis using the cardiovascular electronic system.     

RIGHT SINUS OF VALSALVA ANEURYSM RUPTURE INTO THE RIGHT ATRIUM: PRE- AND POSTOPERATIVE ECHOCARDIOGRAPHIC FINDINGS

Echocardiographic features of a patient with sinus of Valsalva aneurysm rupture into the right atrium are discussed. An abnormal echo representing the aneurysmal sac was seen in the anterior aortic root. Other abnormal echoes were demonstrated in the right atrium. Flutter was visible in systole and diastole in the tricuspid area. The pulmonic valve echogram was normal. After surgical repair, the above findings disappeared.