Elastase-induced Aneurysm Model Research Articles

Testing flow diversion in animal models: a systematic review.

Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

The Derivo Embolization Device, a Second-Generation Flow Diverter for the Treatment of Intracranial Aneurysms, Evaluated in an Elastase-Induced Aneurysm Model.

In recent years, flow diverters have provided a promising alternative to treat complex intracranial aneurysms. In this study, we compare a second-generation flow-diverting device (Derivo Embolization Device) with its prototype flow diverter, in the treatment of elastase-induced aneurysms in New Zealand white rabbits. The Derivo Embolization Device is a self-expanding stent consisting of 48 nitinol wires. The device was implanted across the necks of 17 elastase-induced aneurysms in New Zealand white rabbits. One additional device was implanted in the abdominal aorta of each animal covering the origin of lumbar arteries. Follow-up was performed after 3 months (n = 8) and 6 months (n = 9) under continuous double antiplatelet therapy. Statuses of angiographic and histological aneurysm occlusion as well as patency of branch arteries and neointimal growth were evaluated and compared with its prototype flow diverter. The Derivo Embolization Device provided advanced visibility and flexibility, which led to more accurate navigation and placement. Complete aneurysm occlusion rates were noted in 15 cases (88 %), respectively, compared with 5 cases (28 %) with the first-generation device (p = 0.001). Neointimal growth and diameter stenosis were significantly less with the Derivo Embolization Device and declining after 6 months follow-up in the abdominal aorta. Extreme device oversizing led to distal occlusion of the parent vessel in three cases. Covered branch arteries remained patent throughout the entire period of observation. The Derivo Embolization Device provides excellent occlusion of elastase-induced aneurysms while preserving branch arteries.

Multimodality imaging assessment of the deleterious role of the intraluminal thrombus on the growth of abdominal aortic aneurysm in a rat model.

To evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence. The post-induction growth of the AAA diameter was characterized using ultrasound in 22 rats. ILT was reported on 13 rats that underwent 14 magnetic resonance imaging (MRI) 2-18 days post-surgery, and on 10 rats that underwent 18 fluoro-deoxyglucose (FDG) positron emission tomography (PET)/microcomputed tomography examinations 2-27 days post-surgery. Logistic regressions were used to establish the evolution with time of AAA length, diameter, ILT thickness, volume, stratification, MRI and FDG PET signalling properties, and histological assessment of inflammatory infiltrates. All of the following significantly increased with time post-induction (p < 0.001): AAA length, AAA diameter, ILT maximal thickness, ILT volume, ILT iron content and related MRI signalling changes, quantitative uptake on FDG PET, and the magnitude of inflammatory infiltrates on histology. However, the aneurysm growth peak followed occurrence of ILT approximately 6 days after elastase infusion. Our model emphasizes that occurrence of ILT precedes AAA peak growth. Aneurysm growth is associated with increasing levels of iron, signalling properties changes in both MRI and FDG PET, relating to its biological activities. • ILT occurrence in AAA is associated with increasing FDG uptake and growth. • MRI signalling changes in ILT reflect activities such as haemorrhage and RBC trapping. • Monitoring ILT activities using MRI may require no exogenous contrast agent.

High-flow venous pouch aneurysm in the rabbit carotid artery: A model for large aneurysms.

Currently one of the most widely used models for the development of endovascular techniques and coiling devices for treatment of aneurysm is the elastase-induced aneurysm model in the rabbit carotid artery. Microsurgical techniques for creating an aneurysm with a venous pouch have also been established, although both techniques usually result in aneurysms less than 1 cm in diameter. We investigated whether an increase in blood flow toward the neck would produce larger aneurysms in a microsurgical venous pouch model. Microsurgical operations were performed on 11 New Zealand white rabbits. Both carotid arteries and the right jugular vein were dissected, and the right carotid artery was temporarily clipped followed by an arteriotomy. The left carotid artery was also clipped proximally, ligated distally, and sutured onto the proximal half of the arteriotomy in the right carotid artery. The venous graft was sutured onto the distal half of the arteriotomy. Digital subtraction angiography was also performed. Angiography showed patent anastomosed vessels and aneurysms in the seven surviving rabbits. Mean aneurysm measurements among surviving rabbits with patent vessels were: 13.9 mm length, 9.3 mm width, and neck diameter 4.7 mm. The resulting mean aspect ratio was 3.35 and the mean bottleneck ratio was 3.05. A large venous graft and increased blood flow toward the base of the aneurysm seem to be key factors in the creation of large venous pouch aneurysms. These large aneurysms allow testing of endovascular devices designed for large and giant aneurysms.

Abstract 248: Adipose Stromal Cells Mitigate Excessive Aortic Inflammation and Aortic Aneurysm Expansion through Paracrine Factors in an Elastase-induced Murine Abdominal Aortic Aneurysm Model

Objective: Abdominal aortic aneurysm (AAA) formation is characterized by activation of innate and adaptive immune responses that initiate aortic wall degradation. We hypothesize that human adipose stromal cells (ASC) favorably modulate these immune responses through paracrine mechanisms and attenuate AAA expansion in a murine elastase model. Methods: AAA was induced in C57BL/6 mice by topical treatment of the abdominal aorta with elastase. Human ASC or saline was injected i.v. within 4 hours of elastase treatment. The aortic diameter was measured by ultrasound and video micrometry. Monocytes/macrophages and lymphocyte sub-populations were quantified by flow cytometry. Regulatory T cells (Treg) and M2 macrophages were quantified by immunohistochemical (IHC) staining. ASC were labeled with Hoechst and their distributions in the lung and aorta were imaged by fluorescent microscopy and confirmed by real-time PCR for human-specific Alu sequence. Results: ASC significantly suppressed AAA expansion at 14 days (percent change from baseline: 64.1±4.2% (saline) vs. 24.6±6.2% (ASC), n=10/group, p&lt;0.01). At Day 1 there was a significant increase in Treg in ASC treated mice (n=5/group, p&lt;0.01) with a concurrent decrease of CD4+CD28-, CD8+CD28- T cells, and neutrophils (n=5/group, p&lt;0.05). At Day 7, activated monocytes (CD115+CXCR1-LY6C+) and total aortic tissue resident macrophages were decreased (n=10/group, p&lt;0.05) with a significant polarization to the tissue reparative M2 phenotype (n=5/group, p&lt;0.05). Hoechst labeled ASC were detected in the lung without engraftment in the aorta at 24 hrs and were cleared at 96 hrs. Transmembrane co-culture of human peripheral blood mononuclear cells with ASC induced Treg, polarized macrophages to the M2 phenotype, inhibited neutrophil transmigration, and suppressed lymphocyte proliferation, as further supporting the mechanism of paracrine immunomodulation in the in vivo model of AAA. Conclusion: Systemic injection of ASC significantly induced anti-inflammatory immune cell phenotypes and suppressed AAA formation. These effects are mediated by release of paracrine factors and suggest that further characterization of the ASC secretome may lead to more potent recombinant protein therapies for AAA.

Establishment of a new murine elastase-induced aneurysm model combined with transplantation.

IntroductionThe aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.MethodsAdult male mice (n = 6–9 per group) underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.ResultsMice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11±0.10 mm vs. 0.75±0.03 mm; p≤0,001). Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.ConclusionsWe developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.

Evaluation of a newly designed flow diverter for the treatment of intracranial aneurysms in an elastase-induced aneurysm model, in New Zealand white rabbits.

In this study, we analyzed angiographic and histologic aneurysm occlusion of a newly designed flow-diverting device. Visibility and flexibility, as well as occlusions of side branches and neointimal proliferation were also evaluated. Aneurysms were induced in 18 New Zealand white rabbits and treated with a braided, "closed-loop-designed" device of nitinol. Additional devices were implanted in the abdominal aorta to cover the origin of branch arteries. Angiographic follow-ups were performed immediately after placement of the device, after 3months (n = 9) and 6months (n = 9). The status of aneurysm occlusion (using a five-point scale) and the patency of branch arteries were assessed. Aneurysm occlusion rates were noted as grade 0 in 2 (11%), grade I in 1 (6%), grade II in 1 (6%), grade III in 9 (50%), and grade IV in 5 (28%) of 18 aneurysms, respectively, indicating a complete or near-complete occlusion of 78% under double antiplatelet therapy. Aneurysm occlusion was significantly higher at 6months follow-up (P = 0.025). Radiopaque markers provided excellent visibility. Limited device flexibility led to incomplete aneurysm neck coverage and grade 0 occlusion rates in two cases. Distal device occlusions were found in three cases, most likely due to an extremely undersized vessel diameter in the subclavian artery. No case of branch artery occlusion was seen. Intimal proliferation and diameter stenosis were moderate. The tested flow diverter achieved near-complete and complete aneurysm occlusion under double antiplatelet therapy of elastase-induced aneurysms in 78%, while preserving branch arteries.

CD43-Mediated IFN-γ Production by CD8+ T Cells Promotes Abdominal Aortic Aneurysm in Mice

CD43 is a glycosylated surface protein abundantly expressed on lymphocytes. Its role in immune responses has been difficult to clearly establish, with evidence supporting both costimulatory and inhibitory functions. In addition, its contribution to disease pathogenesis remains elusive. Using a well-characterized murine model of elastase-induced abdominal aortic aneurysm (AAA) that recapitulates many key features of the human disease, we established that the presence of CD43 on T cells is required for AAA formation. Moreover, we found that IFN-γ-producing CD8(+) T cells, but not CD4(+) T cells, promote the development of aneurysm by enhancing cellular apoptosis and matrix metalloprotease activity. Reconstitution with IFN-γ-producing CD8(+) T cells or recombinant IFN-γ promotes the aneurysm phenotype in CD43(-/-) mice, whereas IFN-γ antagonism abrogates disease in wild-type animals. Furthermore, we showed that the presence of CD43 with an intact cytoplasmic domain capable of binding to ezrin-radixin-moesin cytoskeletal proteins is essential for optimal in vivo IFN-γ production by T cells and aneurysm formation. We have thus identified a robust physiologic role for CD43 in a relevant animal model and established an important in vivo function for CD43-dependent regulation of IFN-γ production. These results further suggest that IFN-γ antagonism or selective blockade of CD43(+)CD8(+) T cell activities merits further investigation for immunotherapy in AAA.

Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms

Coiling is the gold standard for the treatment of intracranial aneurysms. However, some issues associated with endovascular treatment limit its long-term efficiency. Recanalization with coil compaction is certainly the most important. New approaches may be considered to promote thrombus colonization by mesenchymal cells and aneurysm healing. In the present study, we have percutaneously delivered autologous bone marrow mesenchymal stem cells (BMSCs) to an elastase-induced rabbit carotid aneurysm model in vivo. Autologous mesenchymatous stem cells were obtained after femoral puncture and bone marrow aspiration. After 2 weeks of in vitro cell culture, five million BMSCs were grafted in the carotid aneurysm using an endovascular approach. We demonstrated the feasibility of in vivo percutaneous seeding of autologous BMSCs in the aneurysm by positive Hoechst fluorostaining. Two weeks later, conventional angiography showed an increase in median aneurysmal surface in the sham group, whereas this surface was decreased in the group treated with BMSCs, +28.4 versus -26.4 %, respectively (p = 0.01). BMSC seeding resulted in intimal hyperplasia with cell colonization and disappearance of the thrombus. In conclusion, percutaneous seeding of BMSCs may colonize and heal the arterial wall thus limiting aneurysm expansion.

A Novel In Vivo Rabbit Model of Abdominal Aortic Aneurysm Induced by Periarterial Incubation of Papain

PurposeThe objective of this study was to determine the possibility of creating a novel animal model of abdominal aortic aneurysm (AAA) in rabbits by the periarterial application of papain. Materials and MethodsTwelve New Zealand white rabbits were randomized into two groups: (1) the papain group, which received 2mg of papain (n=8) and (2) the control group, which received physiologic saline solution (n=4). A 1-cm aortic segment proximal to the bifurcation was isolated, and its adventitia was incubated with papain for 20 minutes. The rabbits underwent intravenous digital subtraction angiography (IVDSA) 5 and 21 days after the operation. The animals were then humanely killed for histomorphometric and immunohistochemical studies. ResultsAll animals in the papain group developed AAA, with an average aneurysm diameter of 4.0±0.6 and 4.1±0.4mm on days 5 and 21, respectively. No aneurysms were seen in the control group. On day 5, the papain-incubated aortas exhibited thinned and disorganized aortic walls, with decreased smooth muscle cells (SMCs) and fragmented and almost nonexistent elastic lamella. Media thickening, intimal hyperplasia, and smooth muscle cell regeneration were obvious on day 21. Immunostaining of matrix metalloproteinase (MMP)-9 and RAM11 showed strong expression in the papain group. On the contrary, the control group did not present histologic alterations and showed almost no expression of MMP-9 and RAM11. ConclusionsA novel in vivo rabbit model of AAA can be induced through periarterial application of papain for 20 minutes. This model is similar to an elastase-induced aneurysm model and could be useful to clarify AAA pathogenesis and endovascular treatment intervention.

In Vivo Assessment of Murine Elastase-induced Abdominal Aortic Aneurysm with High Resolution Magnetic Resonance Imaging

ObjectivesThere are, to date, no published non-invasive or longitudinal studies performed in mice to measure aortic diameter and wall thickness in an elastase-induced abdominal aortic aneurysm. This MRI study at 11.75 T aimed at evaluating the reliability of longitudinal in vivo aortic diameter and wall thickness measurements in this particular model. MethodsAdult male C57BL/6 mice underwent transient elastase or heat-inactivated elastase perfusion (controls). Aortic dilatation was measured before, during and immediately after elastase perfusion, and again 14 days after, with a calibrated ocular grid. MRI was performed just before initial surgery and at day 14 before harvest using an 11.75 T MR microscopy imager. ResultsAortic diameter was significantly greater in elastase-perfused mice compared to controls as measured by optic grid (1.150 ± 0.153 mm vs 0.939 ± 0.07 mm, P = 0.038) and according to MRI measurement of the outer diameter on spin echo images (1.203 ± 0.105 mm vs 1070 ± 0.048 mm, P = 0.0067). Aortic wall thickness was found to be significantly increased in elastase-perfused mice at day 14. ConclusionsThis study demonstrates in the mouse elastase-induced aneurysm model that characterization of aneurysm development by its inner and outer vessel diameter and vessel wall thickness can be carried out longitudinally using high resolution MRI without significant mortality.

Measurement of quantifiable parameters by time-density curves in the elastase-induced aneurysm model: first results in the comparison of a flow diverter and a conventional aneurysm stent

Quantifiable parameters to evaluate the effectiveness of flow diverters (FDs) are desirable. We measured time-density curves (TDCs) and calculated quantifiable parameters in the rabbit elastase-induced aneurysm model after stent (Neuroform [NF]) and FD (Pipeline embolisation device [PED]) treatment. Sixteen rabbit elastase-induced aneurysms were treated with FD (n = 9) or NF (n = 5). Angiography was performed before and after treatment and TDCs were created. The time to peak (TTP), the full width at half maximum (FWHM) and the average slope of the curve which represent the inflow (IF) and outflow (OF) were calculated. Mean values before treatment were TTP = 0.8 s, FWHM = 1.2 s, IF = 153.5 and OF = -54.9. After PED treatment, the TTP of 1.8 s and FWHM of 47.8 s were extended. The IF was 31.2 and the OF was -11.5 and therefore delayed. The values after NF treatment (TTP = 1.1 s, FWHM = 1.8 s, IF = 152.9, OF = -33.2) changed only slightly. It was feasible to create TDCs in the rabbit aneurysm model. Parameters describing the haemodynamic effect of PED and NF were calculated and were different according to the type of device used. These parameters could possibly serve as predictive markers for aneurysm occlusion.

Comparison of the In Vitro Hemodynamic Performance of New Flow Diverters for Bypass of Brain Aneurysms

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p > 0.05).

Bone marrow-derived endothelial progenitor cells are involved in aneurysm repair in rabbits

Endothelial progenitor cells (EPC) are believed to be involved in aneurysmal repair and remodeling. The aim of this study was to test this hypothesis and, if true, explore how EPC contribute to aneurysm repair in a rabbit model of elastase-induced carotid aneurysm. Rabbits were divided randomly into an in situ carotid EPC transfusion group (ISCT group, n=5), and an intravenous EPC transfusion group (IVT group, n=5). Autologous EPC were double-labeled with Hoechst 33342 and 5,6-carboxyfluorescein diacetate succinimidyl ester before injection into the animals in either the carotid artery (ISCT group) or marginal ear veins (IVT group). Three weeks later, labeled cells in the aneurysms were observed with respect to location, adhesion, and growth to detect signs of aneurysm repair. Labeled EPC were detected within the neointima in all five aneurysms in the ISCT group and in three of the five aneurysms in the IVT group, but there was no endothelial growth in the aneurysmal neointima in either group. These results show that bone marrow-derived EPC are involved in the process of aneurysm repair in this rabbit model.

Elastase-Induced Rabbit Aneurysms Model Complicated by Thoracic Aortic Aneurysms: Fig 1.

Published reports have described the elastase-induced aneurysm model in rabbits as easy and reproducible and possessing geometric, pathologic, and hemodynamic features that are similar to those of human cerebral aneurysms.[1][1] We used a simple surgical technique to produce the elastase-induced

Can aspect ratio be used to categorize intra-aneurysmal hemodynamics?—A study of elastase induced aneurysms in rabbit

Clinical studies suggest that aneurysm aspect ratio (AR) is an important indicator of rupture likelihood. The importance of AR is hypothesized to arise from its influence on intra-aneurysmal hemodynamics. It has been conjectured that slower flow in high AR sacs leads to a cascade of biological activities that weaken the aneurysm wall ( Ujiie et al.,1999). However, the connection between AR, hemodynamics and wall weakening has never been proven. Animal models of saccular aneurysms provide a venue for evaluating this conjecture. The focus of this work was to evaluate whether a commonly used elastase induced aneurysm model in rabbits is suitable for a study of this kind from a hemodynamic perspective. In particular, to assess whether hemodynamic factors in low and high AR sacs are statistically different. To achieve this objective, saccular aneurysms were created in 51 rabbits and pulsatile computational fluid dynamics (CFD) studies were performed using rabbit specific inflows. Distinct hemodynamics were found in the low AR (AR<1.8, n=25), and high AR (AR>2.2, n=18) models. A single, stable recirculation zone was present in all low AR aneurysms, whereas a second, transient recirculation zone was also found in the superior aspect of the aneurysm dome for all high AR cases. Aneurysms with AR between 1.8 and 2.2 displayed transitional flow patterns. Differences in values and distributions of hemodynamic parameters were found between low and high AR cases including time averaged wall shear stress, oscillatory shear index, relative residence time and non-dimensional inflow rate. This work lays the foundation for future studies of the dependence of growth and remodeling on AR in the rabbit model and provides a motivation for further studies of the coupling between AR and hemodynamics in human aneurysms.

Protective effects of Resveratrol in an experimental model of abdominal aortic aneurysm induction

Resveratrol (Rsv) is a natural antioxidant polyphenol with vasoprotective properties. We evaluated whether Rsv affects the inflammatory response in an experimental model of elastase-induced abdominal aortic aneurysm. Thirty male rats were subjected to aneurysm induction and treated or not with Rsv. Circulating levels of CD62L-monocyte subset, monocyte CD I 43 surface expression, MMP-9 plasma activity and TNFα serum levels were lower in Rsv-treated rats. In conclusion. Rsv acts as an anti-inflammatory compound and could be of great revelance to improve the immune response in AAA patients.

Hemodynamics and Anatomy of Elastase-Induced Rabbit Aneurysm Models: Similarity to Human Cerebral Aneurysms?

Animal models provide a mechanism for fundamental studies of the coupling between hemodynamics and pathophysiology in diseases such as saccular aneurysms. In this work, we evaluated the capability of an elastase-induced saccular aneurysm model in rabbits to reproduce the anatomic and hemodynamic features typical for human intracranial aneurysms. Saccular aneurysms were created in 51 rabbits at the origin of the RCCA. Twelve weeks' postcreation, the lumen geometry of the aneurysm and surrounding vasculature was acquired by using 3DRA. Geometric features of these models were measured. Pulsatile 3D CFD studies were performed with rabbit-specific inlet profiles. Geometric features, including aneurysm height, width, neck diameter, aspect ratio, and NSI of all 51 rabbit aneurysm models fell within the range reported for human IAs. The distribution and range in values of pressure, WSS, and OSI were also typical for human IAs. A single recirculation region was observed in 33 (65%) of 51 cases, whereas a second transient recirculation zone was observed in 18 (35%) cases. Both of these flow types are commonly observed in human IAs. Most hemodynamic and geometric features in a commonly used elastase-induced rabbit saccular aneurysm model are qualitatively and quantitatively similar to those seen in large numbers of human cerebral aneurysms.

Assessment of Elastase‐Induced Murine Abdominal Aortic Aneurysms: Comparison of Ultrasound Imaging with In Situ Video Microscopy

Aims. The aim of this study was to definitively assess the validity of noninvasive high-frequency ultrasound (US) measurements of aortic luminal diameter (ALD) in a murine model of elastase-induced abdominal aortic aneurysm in comparison with in situ video microscopy (VM). Methods. C57BL/6 mice underwent transient perfusion of the aorta with either elastase (n = 20: Elastase group) or saline (n = 10: Sham). Unoperated mice (n = 10) were also studied. Results. ALD measurements by US had excellent linear correlation and absolute agreement with that by VM in both Control (unoperated or sham-operated mice) and elastase groups (r = 0.96, intraclass correlation coefficient (ICC) = 0.88 and r = 0.93, ICC = 0.92, resp.). Bland-Altman analysis of US compared with VM measurements in both groups indicated good agreement, however US measurements were slightly but significantly higher than VM measurements in the control group (mean bias 0.039 mm, P < .05). Linear regression analysis revealed excellent correlation between US and VM measurements in both groups. (R2 = 0.91 in Control group, R2 = 0.85 in elastase group.) The reliability of US measurements was also confirmed by ex vivo histological measurements. Conclusions. High-frequency US provides reliable ALD measurements in developing murine abdominal aortic aneurysms.

Study of relationship between formation of internal carotid artery aneurysm and changes of vascular smooth muscle cells in rabbits

Objective To developmental changes in vascykar smooth muscle cells(VSMC)during abeyrtsm formation using an elastase-induced rabbit carotid artery aneurysm model. Methods Aneurysm was induced in carotid arteries of rabbits by exposure to elastase. Tissues from developing aneurysms were isolated at various time points for histological, immunohistochemical and RT-PCR analysis. Results During the aneurysm growth, the vascular media became thinner and elastic fibers became fragmented.The expression of smooth muscle marker SM22α-mRNA and cytoskeleton proteins (SM α-actin, β-Tubulin and Desmin) expression was decreased while platelet-derived growth factor (PDGF) was increased, which correlated with a remodeling of VSMC from contractiler to synthetic functions. Conclusion During the development of aneurysm, VSMC is remodeled from the contractile phenotype to a synthetic phenotype as a potential repair mechanism. Further studies may reveal the causative effects between these events. Key words: Aneurysm; Vascular smooth muscle cells; Phenotype; Cytoskeleton proteins