Greater Risk Of Rupture Research Articles

311 Rupture-Risk Stratifying Patients With Cerebral Arteriovenous Malformations Using Quantitative Hemodynamic Flow Measurements

INTRODUCTION: Up to 60% of cerebral arteriovenous malformations (AVMs) present with an intracranial hemorrhage, however, noninvasive neuroimaging has increasingly diagnosed incidental AVMs. AVM management depends on weighing the lifetime rupture risk against the risks of intervention. Although AVM rupture risk relies primarily on angioarchitectural features, measuring hemodynamic flow is gaining traction. An accurate understanding of AVM hemodynamic flow parameters will help stratify patients by rupture risk and select treatment plans. METHODS: The literature was reviewed for articles that quantified AVM flow. RESULTS: Quantitative digital subtraction angiography (QDSA), 4D spin-labeled magnetic resonance angiography (4D-SL-MRA), and 4D-Flow magnetic resonance imaging (4D-Flow-MRI) studies measure relative flow; 3D phase-contrast MRI (PC-MRI) studies measure relative and true flow; and quantitative MRA (QMRA) studies measure true flow. QDSA studies have correlated increased rupture risk with prolonged venous outflow, however there are mixed findings with respect to arterial inflow. Similarly, a higher AVM inflow-to-outflow ratio has been associated with greater rupture risk in studies using PC-MRI. 4D-SL-MRA studies, on the other hand, have demonstrated a lower time-to-peak draining-vein-to-feeder-artery ratio in patients with AVM rupture. Finally, 4D-Flow-MRI studies have shown inconsistent findings whereas QMRA studies have found no significant associations between AVM hemodynamic flow parameters and rupture risk. CONCLUSIONS: Quantitative hemodynamic studies on the relationship between AVM flow and rupture risk have not reached a clear consensus; however, the preponderance of data suggests that higher arterial inflow and lower venous outflow in the AVM nidus contribute to increased hemorrhagic risk. Future studies should consider using larger sample sizes and standardized definitions of hemodynamic parameters to reach a consensus. In the meantime, classic angioarchitectural features may be more strongly correlated with AVM rupture than the amount of blood flow.

A case report of endovascular treatment of a fast-growing inflammatory abdominal aortic aneurysm in a patient with Staphylococcus aureus sepsis

Abdominal Aortic Aneurysm (AAA) and its subsequent rupture is one of the life-threatening conditions. The most common type of arterial aneurysm, AAA, becomes significant at a diameter greater than 3 cm. The mean growth rate of an AAA is 2-3 mm per year, and surgical repair is usually recommended if the diameter exceeds 5.5 cm, in men and 5.0 to 5.2 cm, in women. Faster-growing aneurysms are more aggressive and have a greater risk of rupture. We report a case of a 64-year-old, comorbid male patient who was found to have a previously unknown, but a rapidly growing AAA, which grew from 6cm to 8 cm within just 3 weeks. He was admitted in the emergency department with complaints of worsening dyspnea even without exertion. Upon thorough diagnostic tests, the severity of the overall medical condition was determined by S. aureus sepsis, decompensation of cardiovascular disease, and secondary kidney injury due to septic shock. While receiving treatment for sepsis, a diagnostic CT imaging was done, which confirmed bilateral pneumonia and retroperitoneal abscess in m. psoas major mass, and an infrarenal abdominal aortic aneurysm, which was 6cm in diameter at the time of diagnosis. Another control CT of the lungs and abdomen was performed three weeks later, indicating the pneumonia was slowly resolving, while the aortic aneurysm increased in dynamic; the diameter was 8 cm with a penetrating exudation on the left side, m. psoas abscess was still observed, but decreasing. Because the AAA was very fast-growing, it greatly increased the risk of its rupture, therefore a decision was made to perform endovascular abdominal aortic aneurysm repair, despite the risk of stent infection, given the patients septic background. The goal of this case report is to highlight the rare case of a rapidly growing inflammatory aneurysm and its successful endovascular management. While it’s known that 5-10% of all AAA are inflammatory, cases of surgical treatment in the setting of sepsis are basically non-existent in the literature [1].

Review of human supraspinatus tendon mechanics. Part II: tendon healing response and characterization of tendon health.

Overuse injuries of the rotator cuff, particularly of the supraspinatus tendon (SST), are highly prevalent and debilitating in work, sport, and daily activities. Despite the clinical significance of these injuries, there remains a large degree of uncertainty regarding the pathophysiology of injury, optimal methods of nonoperative and operative repair, and how to adequately assess tendon injury and healing. The tendon response to fatigue damage resulting from overuse is different from that of acute rupture and results in either an adaptive (healing) or a maladaptive (degenerative) response. Factors associated with the degenerative response include increasing age, smoking, hypercholesterolemia, biological sex (variable by tendon), diabetes mellitus, and excessive load post fatigue damage. After injury, the average healing rate of tendon is approximately 1% per day and may be significantly influenced by biologic sex (females have lower collagen synthesis rates) and excessive load after damage. Although magnetic resonance imaging (MRI) is considered the gold standard in assessing acute tears as well as tendinopathic change in the SST, ultrasonography has proven to be a valuable tool to measure tendinopathic change in real time. Ultrasonography can determine multiple mechanical and structural parameters of the SST that are altered in fatigue loading. Thus, ultrasonography may be utilized to understand how these parameters change in response to SST overuse, and may aid in determining the activity level that places the SST at greater risk of rupture.

Abstract 14293: Sex Differences in Cytokine and Chemokine Expression in an Experimental AAA Rodent Model

Introduction: Abdominal aortic aneurysms (AAAs) are a multifactorial disease process that results from a series of biomolecular processes. AAAs are more prevalent in men; however, women are at greater risk of rupture. Despite continued investigation, the mechanisms of sex disparities in AAA remain unknown. Hypothesis We hypothesize that male and female rats will have different inflammatory cytokine and chemokine expression in AAA tissue. Methods: Male and female Sprague-Dawley rats underwent intraluminal infrarenal abdominal aortic exposure to elastase to induce AAA. Rats were administered daily β-aminopropionitrile to promote AAA rupture. In vivo aortic diameters were evaluated using ultrasound (12MHz) at day 7 and 14 post-AAA induction. PET imaging with 64 Cu-DOTA-ECL1i (a selective radio-marker for C-C chemokine receptor type 2; CCR2), AAA tissue zymography and cytokine array were performed at day 6 and 14 to evaluate CCR2, matrix metalloproteinases (MMP), chemokine, and cytokine content. Results: Male rats developed larger AAAs at day 7 and 14 compared to female rats (p<0.0001; Figure 1A), but AAA rupture rate was similar between sexes. At day 6, AAA cytokine arrays demonstrated Rantes, IFN-y, and IL-17A were higher in males (p<0.01; Figure 1B-D). However, MCP-1, IL-6, IL-10, IL-18, IL-1B, and TNF-α were similar between groups (Figure 1E-J). Interestingly, at day 14, females showed significantly higher MCP-1, IL-6, and IL-10 (p<0.05; Figure 1E-G). PET imaging demonstrated that males had higher CCR2 uptake at day 14 (p<0.05; Figure 1K). AAA zymography demonstrated equivalent levels of total MMP-9, pro-MMP 9, and active MMP-9 between groups (Figure 1L-O). Conclusion Our findings demonstrated that inflammatory cytokines and chemokines are differentially expressed in AAA tissue - particularly CCR2 which is higher in males. This provides sex-specific AAA tissue targets for diagnostic molecular imaging and potential future immune-modulation strategies.

Relationship between anterior cruciate ligament rupture and the posterior tibial and meniscal slopes in professional soccer athletes.

Several anatomical parameters have been associated with increased risk of anterior cruciate ligament rupture; however, published studies provide conflicting results. The objectives of this study are to assess whether there is a relationship between anterior cruciate ligament rupture and the lateral and medial posterior tibial slopes, as well as the lateral and medial posterior meniscal slopes and posterior tibial and meniscal delta-slopes. A retrospective case-control study was conducted in professional soccer athletes, using images from knee magnetic resonance imaging scans in athletes with clinical and radiological diagnosis of anterior cruciate ligament rupture, and control group, with no signs of ligament rupture. The lateral and medial posterior tibial slopes, the lateral and medial posterior meniscal slopes, and the posterior tibial and meniscal delta-slopes showed significant differences between the groups (p < 0.05). Multivariate analysis logistic regression revealed that the lateral and medial posterior meniscal slopes proved to be predictors for increased risk of anterior cruciate ligament rupture in professional soccer players. Posterior tibial and meniscal slopes and tibial and meniscal delta-slopes are related to a greater risk of rupture of the anterior cruciate ligament in professional male soccer athletes. The lateral and medial posterior meniscal slopes are predictors for ligament rupture.

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischaemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture. Statement of significanceMechanical characterisation of the atherosclerotic plaque cap is of utmost importance for understanding the mechanisms that govern the rupture strength of this tissue in-vivo. Studies has shown that plaque tissue is heterogenous and comprises of many structural components, each of which exhibits a varying mechanical response. However, rupture generally is located to the plaque cap, whereby the stress exerted on this location exceeds its mechanical strength causing failure. This work shows, for the first time, that the underlying collagen fibre architecture of carotid plaque caps governs their strength and stiffness. This study shows that plaque caps with collagen fibres aligned in the predominately circumferential direction experience higher stresses and lower strains before failure while those with predominately axial fibres display the opposite trend. Furthermore, total collagen content was found not to play a dominant role in determining the mechanical response of the tissue. The present study provides critical insights into human atherosclerotic plaque tissue mechanics and offers clinically relevant insights for mechanically sensitive imaging techniques, such as strain-based ultrasound or MRI.

Significance of aneurysm wall enhancement on high-resolution vessel wall magnetic resonance imaging in clinical management of patients with intracranial aneurysms.

The prevalence of intracranial aneurysms is estimated to be around 3% in the general population. Although these are often incidental findings, they potentially carry the risk of rupture, with all of the devastating consequences of SAH. Several risk factors of aneurysm rupture have been identified, including aneurysm size, irregular shape, and location. Although it is widely accepted that the risk of rupture increases with size, small aneurysms remain the cause of a significant percentage of aneurysmal SAH. Up to 30% of patients with acute aneurysmal SAH have multiple aneurysms. Determining the site of rupture in these patients can be challenging, given that the results of imaging studies and clinical symptoms are sometimes inconclusive. It would be extremely useful to identify new imaging biomarkers of aneurysm instability which could have an impact on patient management and qualification for treatment. High-resolution vessel wall magnetic resonance imaging (HR-VW MRI) opens up new possibilities for improved characterisation of intracranial vasculature. One of the most promising clinical applications of this new imaging tool is the evaluation of intracranial aneurysms. Aneurysm wall enhancement (AWE) on HR-VW MRI is believed to be a marker for wall inflammation and, potentially, for aneurysm instability. In this article, we summarise the published literature on AWE with special emphasis on its use in determining the site of rupture in the setting of acute SAH in patients with multiple aneurysms, as well as its role in identifying unruptured aneurysms which are at the greatest risk of rupture. More and larger studies are needed to definitively establish the role of AWE on HR-VW MRI in the diagnostic workup of patients with intracranial aneurysms.

The functional limits of the aneurysmal aortic root. A unique pressure testing apparatus

BackgroundThe aortic root has unique embryological development and is a highly sophisticated and complex structure. In studies that report on the biomechanical characteristics of the thoracic aorta, distinction between the aortic root and ascending aorta regions is nonexistent. Our objective is to determine the maximal pressures at which dissection occurs or tissue failure occurs in the aortic root compared to that of the ascending aorta in the presence of aortic aneurysms. This may help guide preoperative monitoring, diagnosis and the decision for operative intervention for aortic root aneurysms in the normal and susceptible populations.MethodsWe developed a simple aortic root and ascending aorta pressure testing unit in series. Ten fresh porcine hearts were obtained from the local abattoir (n = 5 aortic root and n = 5 ascending aorta for comparison). Using a saline filled needle and syringe, artificial fluid-filled aneurysms were created between the intima and medial layers of the aortic root. The aorta lumen was then progressively filled with saline solution. Pressure measurement was taken at time of loss of tissue integrity, obvious tissue dissection or aneurysm rupture, and the tissue structure was then visually examined.ResultsIn the aortic root, mean maximal pressure (mmHg) at tissue failure was 208 mmHg. Macroscopic examination revealed luminal tears around the coronary ostia in 2/5 specimens, and in all specimens, there was propagation of the dissection in the aortic root in a circumferential direction. In all ascending aorta specimens, the maximal aortic pressures exceeded 300 mmHg without tissue failure or dissection, and eventual apparatus failure.ConclusionOur results indicate that the aneurysmal aortic root tissues are at greater risk of rupture and dissection propagation at lower aortic pressure. With further analysis, this could guide clinical and surgical management.

Increased m6A methylation level is associated with the progression of human abdominal aortic aneurysm.

The role of N6-methyladenosine (m6A) modification in abdominal aortic aneurysm (AAA) has not been extensively studied. This study therefore aimed to investigate m6A RNA methylation and the expressions of the corresponding modulators in AAA. A comparative study between AAA tissue samples (n=32) and healthy aortas (n=12) was performed using m6A methylation quantification for messenger RNA (mRNA) m6A status, quantitative polymerase chain reaction (qPCR), and western blot for the expressions of m6A modulators and immunohistochemistry (IHC) to detect locations of the modulators in AAA tissues. The m6A level significantly increased in AAA as compared to healthy aorta tissues. Among AAA patients, the high m6A level represented an even greater risk of AAA rupture as compared to non-ruptured AAA [odds ratio (OR), 1.370; 95% confidence interval (CI), 1.007-1.870]. The major N6-adenosine modulators, including YTHDF1, YTHDF3, FTO, and METTL14, are the main factors involved in aberrant m6A modification and the expression of both was significantly correlated to the proportion of m6A in total mRNA. Clinically, YTHDF3 represented an even greater risk of rupture (OR, 1.036; 95% CI, 1.001-1.072). Regarding the cellular location, METTL14 seemed to be associated with inflammatory infiltrates and neovascularization. Furthermore, a strong correlation was seen between FTO and aneurysmal smooth muscle cells (SMCs), YTHDF3, and macrophage infiltrate. We were first to observe m6A modification in human AAA tissues. The results also reveal the important roles of m6A modulators, including YTHDF3, FTO, and METTL14, in the pathogenesis of human AAA and provide a new view on m6A modification in AAA. Our findings suggest a potential mechanism of epigenetic alterations in clinical AAA.

Sex differences in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Risk factors for ruptured intracranial aneurysms.

Background & objectives:The treatment of unruptured intracranial aneurysms (IAs) remains controversial; the ability to predict the risk of rupture for an aneurysm would be of clinical value. The aim of this study was to determine and evaluate the predictive value of the risk factors of IA rupture.Methods:This retrospective study involved 379 consecutive patients with 441 aneurysms between August 2011 and July 2014. Based on clinical data and computed tomography angiography findings, the potential of risk factors to predict the aneurysmal rupture was assessed using statistical methods.Results:Age, hypertension, heart disease, diabetes mellitus, cerebral atherosclerosis, aneurysms located at the internal carotid artery (ICA) and neck width (N) correlated negatively with rupture risk. Aneurysms located at the anterior communicating artery, bifurcation, irregularity, with a daughter sac, aneurysm height, maximum size, aspect ratio (AR), height-to-width ratio and bottleneck factor were significantly and positively correlated with rupture risk. The multivariate logistic regression model revealed that bifurcation aneurysm, irregular aneurysm and high AR increased the rupture risk, while cerebral atherosclerosis, aneurysm located on the ICA and greater N decreased the risk. Receiver operating characteristic analysis of AR curve values differed according to circumstances.Interpretation & conclusions:Cerebral atherosclerosis, location in the ICA and larger N were the protective factors against aneurysm rupture, and IAs located at bifurcations, irregular shape and increased AR indicated a greater rupture risk.

Scaling of the ankle extensor muscle-tendon units and the biomechanical implications for bipedal hopping locomotion in the post-pouch kangaroo Macropus fuliginosus.

Bipedal hopping is used by macropods, including rat-kangaroos, wallabies and kangaroos (superfamily Macropodoidea). Interspecific scaling of the ankle extensor muscle-tendon units in the lower hindlimbs of these hopping bipeds shows that peak tendon stress increases disproportionately with body size. Consequently, large kangaroos store and recover more strain energy in their tendons, making hopping more efficient, but their tendons are at greater risk of rupture. This is the first intraspecific scaling analysis on the functional morphology of the ankle extensor muscle-tendon units (gastrocnemius, plantaris and flexor digitorum longus) in one of the largest extant species of hopping mammal, the western grey kangaroo Macropus fuliginosus (5.8-70.5 kg post-pouch body mass). The effective mechanical advantage of the ankle extensors does not vary with post-pouch body mass, scaling with an exponent not significantly different from 0.0. Therefore, larger kangaroos balance rotational moments around the ankle by generating muscle forces proportional to weight-related gravitational forces. Maximum force is dependent upon the physiological cross-sectional area of the muscle, which we found scales geometrically with a mean exponent of only 0.67, rather than 1.0. Therefore, larger kangaroos are limited in their capacity to oppose large external forces around the ankle, potentially compromising fast or accelerative hopping. The strain energy return capacity of the ankle extensor tendons increases with a mean exponent of ~1.0, which is much shallower than the exponent derived from interspecific analyses of hopping mammals (~1.4-1.9). Tendon safety factor (ratio of rupture stress to estimated peak hopping stress) is lowest in the gastrocnemius (< 2), and it decreases with body mass with an exponent of -0.15, extrapolating to a predicted rupture at 160 kg. Extinct giant kangaroos weighing 250 kg could therefore not have engaged in fast hopping using 'scaled-up' lower hindlimb morphology of extant western grey kangaroos.

Influence of Carotid Siphon Anatomy on Brain Aneurysm Presentation.

Intracranial aneurysm is a devastating disease of complex etiology that is not fully understood. The purpose of this study was to assess the implications of carotid siphon anatomy for the formation and development of intracranial aneurysms. Between January 2007 and May 2015, lateral view digital subtraction angiographic images of 692 consecutive patients with intracranial aneurysms treated in our department of interventional neuroradiology were reviewed and had their angles measured. Data on the location, presentation, and size of the lesions were collected and evaluated by multivariate analysis in relation to the measured angles. Of 692 aneurysms, 225 (32.51%) ruptured and 467 (67.49%) unruptured, 218 (31.50%) were in the carotid siphon and 474 (68.50%) were distal to the siphon, and the mean aneurysm size was 7.99 ± 6.95 mm. Multivariate analysis showed an association between angles of >15.40° and rupture (P = .005), postsiphon location (P = .034), and aneurysm size of >1.001 mm (P = .015). Multivariate analysis also showed that every 1-year increase in patient age produced an increase of 1.002 mm in aneurysm size (P = .015). There was a significant independent direct relation of greater anterior knee angle with intracranial aneurysms located distal to the carotid siphon, larger aneurysms, and greater risk of rupture. These findings may be associated with the hemodynamic interactions of blood flow and the curvature of the carotid siphon.

Abstract 107: Increased Peak Wall Stress in Women With Abdominal Aortic Aneurysms

Objective: Women with abdominal aortic aneurysms (AAA) exhibit more rapid aneurysm growth and greater rupture risk at equivalent diameters relative to men. Evidence suggests that biomechanical peak wall stress (PWS) derived from finite element analysis of AAAs is a superior predictor of rupture compared to maximum transverse diameter (MTD). This study aimed to investigate differences in the calculated PWS of AAAs between men and women. Method: Men (n=35) and women (n=35) with infrarenal AAAs with 45-55mm MTD undergoing CTA were identified. Customized image processing algorithms extracted patient-specific AAA geometries from raw DICOM images. The resulting aortic reconstructions incorporated patient-specific and regionally resolved aortic wall thickness, intraluminal thrombus, and wall calcifications. Aortic models were loaded with 120mmHg blood pressure using commercially available FEA solvers. Results: Peak wall stress was found to be significantly higher in women (299±51 vs 257±53 kPA, P=0.001, see Figure). Neither MTD (50.5±3.1 vs 49.8±2.9 mm, P=0.34), mean aortic wall thickness (2.38±0.52 vs 2.34±0.50 mm, P=0.69), nor wall thickness at location of PWS (2.36±0.60 vs 2.20±0.46 mm, P=0.20) varied by sex. While there were no sex-associated differences in aneurysm volume (86.6±27.0 vs 94.8±25.5 cm 3 , P=0.76) or intraluminal thrombus volume (14.2±11.7 vs 16.3±13.4 mm, P=0.33), women’s AAAs had significantly increased maximum Gaussian curvature (0.032±0.011 vs 0.025±0.015 mm -2 , P=0.03). Conclusion: Comparably sized AAAs in women were shown to have significantly higher peak wall stress. Maximum gaussian curvature, a measure of aneurysm morphology, was significantly different between the two groups. These results suggest that men and women possess distinct aneurysm geometries, and that PWS-derived rupture risk prediction may provide a more reliable estimator of rupture risk in all patients.

Aetiology and pathogenesis of cranial cruciate ligament rupture in cats by histological examination.

Objectives The aim of this study was to examine histologically intact and ruptured cranial cruciate ligaments in cats, in order to evaluate whether degeneration is a prerequisite for rupture. Methods We performed a histological examination of 50 intact and 19 ruptured cranial cruciate ligaments in cadaver or client-owned cats, respectively, using light microscopy. Cats with stifle pathology were further divided into five age groups in order to investigate the relationship of changes in the ligament with lifespan. Cats with ruptured cranial cruciate ligaments were divided into two groups according to medical history (with presumed history of trauma or without any known history of trauma) in order to investigate the relationship of ligament rupture with a traumatic event. Data from 200 healthy cats were selected randomly and reviewed to make a statistical comparison of cats with and without cranial cruciate ligament rupture (reference group). Results On histological examination, the intact cranial cruciate ligaments showed basic parallel arrangement of the collagen fibres, with no relation to age. While cats of a more advanced age showed fibrocartilage in the middle of the cranial cruciate ligament - a likely physiological reaction to compression forces over the lifespan - degenerative changes within the fibrocartilage were absent in all cases, regardless of age or rupture status. Cats suffering from cranial cruciate ligament rupture without history of trauma were significantly older than cats in the reference group. Conclusions and relevance This study showed that differentiation of fibrocartilage in the middle of the cranial cruciate ligament is likely a physiological reaction to compressive forces and not a degenerative change associated with greater risk of rupture in advanced age. This finding in cats is distinct from the known decrease in differentiation of fibrocartilage in dogs with cranial cruciate ligament rupture. Furthermore, the histological examination of cats revealed no other signs of degeneration in the cranial cruciate ligaments. Thus, degeneration is likely not an aetiological factor for cranial cruciate ligament rupture in cats.

Inflammation and intracranial aneurysms: mechanisms of initiation, growth, and rupture

Outcomes following aneurysmal subarachnoid hemorrhage remain poor in many patients, despite advances in microsurgical and endovascular management. Consequently, considerable effort has been placed in determining the mechanisms of aneurysm formation, growth, and rupture. Various environmental and genetic factors are implicated as key components in the aneurysm pathogenesis. Currently, sufficient evidence exists to incriminate the inflammatory response as the common pathway leading to aneurysm generation and rupture. Central to this model is the interaction between the vessel wall and inflammatory cells. Dysfunction of the endothelium and vascular smooth muscle cells (VSMCs) promotes a chronic pathological inflammatory response that progressively weakens the vessel wall. We review the literature pertaining to the cellular and chemical mechanisms of inflammation that contribute to aneurysm development. Hemodynamic stress and alterations in blood flow are discussed regarding their role in promoting chronic inflammation. Endothelial cell and VSMC dysfunction are examined concerning vascular remodeling. The contribution of inflammatory cytokines, especially tumor necrosis factor-α is illustrated. Inflammatory cell infiltration, particularly macrophage-mediated deterioration of vascular integrity, is reviewed. We discuss the inflammation as a means to determine aneurysms at greatest risk of rupture. Finally, future therapeutic implications of pharmacologic modulation of the inflammation are discussed.

Relative importance of aneurysm diameter and body size for predicting abdominal aortic aneurysm rupture in men and women

Women have been shown to have up to a fourfold higher risk of abdominal aortic aneurysm (AAA) rupture at any given aneurysm diameter compared with men, leading to recommendations to offer repair to women at lower diameter thresholds. Although this higher risk of rupture may simply reflect greater relative aortic dilatation in women who have smaller aortas to begin with, this has never been quantified. Our objective was therefore to quantify the relationship between rupture and aneurysm diameter relative to body size and determine whether a differential association between aneurysm diameter, body size, and rupture risk exists for men and women. We performed a retrospective review of all patients in the Vascular Study Group of New England (VSGNE) database who underwent endovascular or open AAA repair. Height and weight were used to calculate each patient's body mass index and body surface area (BSA). Next, indices of each measure of body size (height, weight, body mass index, BSA) relative to aneurysm diameter were calculated for each patient. To generate these indices, we divided aneurysm diameter (in cm) by the measure of body size; for example, aortic size index (ASI) = aneurysm diameter (cm)/BSA (m(2)). Along with other relevant clinical variables, we used these indices to construct different age-adjusted and multivariable-adjusted logistic regression models to determine predictors of ruptured repair vs elective repair. Models for men and women were developed separately, and different models were compared using the area under the curve. We identified 4045 patients (78% male) who underwent AAA repair (53% endovascular aortic aneurysm repairs). Women had significantly smaller diameter aneurysms, lower BSA, and higher BSA indices than men. For men, the variable that increased the odds of rupture the most was aneurysm diameter (area under the curve = 0.82). Men exhibited an increased rupture risk with increasing aneurysm diameter (<5.5 cm: odds ratio [OR], 1.0; 5.5-6.4 cm: OR, 0.9; 95% confidence interval [CI], 0.5-1.7; P = .771; 6.5-7.4 cm: OR, 3.9; 95% CI, 1.9-1.0; P < .001; ≥ 7.5 cm: OR, 11.3; 95% CI, 4.9-25.8; P < .001). In contrast, the variable most predictive of rupture in women was ASI (area under the curve = 0.81), with higher odds of rupture at a higher ASI (ASI >3.5-3.9: OR, 6.4; 95% CI, 1.7-24.1; P = .006; ASI ≥ 4.0: OR, 9.5; 95% CI, 2.3-39.4; P = .002). For women, aneurysm diameter was not a significant predictor of rupture after adjusting for ASI. Aneurysm diameter indexed to body size is the most important determinant of rupture for women, whereas aneurysm diameter alone is most predictive of rupture for men. Women with the largest diameter aneurysms and the smallest body sizes are at the greatest risk of rupture.

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

BackgroundAn 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.MethodsA 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.ResultsThe 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 εc and was 47.3% for specimens with εc = 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 εc <10% and εc >30%, respectively. Among specimens ruptured within the cylinder, 93% of those obtained from the mid-media showed crack initiation at the thin center area.ConclusionsAortic 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.

The Natural Course of Unruptured Cerebral Aneurysms

The Natural Course of Unruptured Cerebral Aneurysms

Hemodynamics of small aneurysm pairs at the internal carotid artery

Cerebral aneurysms carry significant risks because rupture-related subarachnoid hemorrhage leads to serious and often fatal consequences. The rupture risk increases considerably for multiple aneurysms. Multiple aneurysms can grow from the same location of an artery, and the interaction between these aneurysms raises the rupture risk even higher. Four aneurysm pair cases at the internal carotid artery are investigated for their hemodynamic behaviors using patient-specific modeling. For each case, aneurysms are separated from the parent artery and three models are reconstructed, one with two aneurysms and the other two models with only one of the two aneurysms. Results show that the relative anatomic location of one aneurysm to the other may determine the hemodynamic environment of an aneurysm. The presence of a proximal aneurysm reduces the intra-aneurysmal flow into the distal aneurysm; the proximal aneurysm and larger aneurysm have a greater area under low wall shear stress. The average intra-aneurysmal inflow ratio ranges from 16% to 41%, and reduction of the inflow ratio by an aneurysm pair varies from 6% to 15%. The maximum wall shear stress increases for serial aneurysms, but decreases for parallel aneurysms. Interaction between parallel aneurysms is not significant; however, the proximal aneurysm in serial aneurysms may be subject to a greater rupture risk.