Elastase-induced Aneurysms In Rabbits Research Articles

How the elastase-induced rabbit aneurysm heals following flow diverter treatment: a histopathological study.

Fibrin deposition is integral to thrombus formation and wound healing. The role of fibrin deposition and subsequent metabolism following flow diversion for aneurysm treatment remains poorly characterized. This study aimed to evaluate the role of fibrin in early thrombus organization after flow diverter treatment. Thirty-five elastase-induced aneurysms were induced in New Zealand white rabbits and subjected to endoluminal flow diversion treatment. The device-bearing arteries were harvested at 1, 3, and 6 months postimplantation and processed for histopathological examination, including a modified picro-Mallory stain (Carstairs method) to visualize fibrin and platelets, immunohistochemical targeting of smooth muscle actin (SMA), and H&E staining for conventional morphological evaluation. Quantitative analysis of tissue components was carried out using the Orbit Image Analysis software. The samples were also assessed qualitatively to investigate the morphology and location of fibrin and other thrombus components within the intra-aneurysmal thrombi. Statistical analyses were conducted using R software version 4.3.1. Fibrin constituted 27.9% of the thrombus tissue within the aneurysm sac for aneurysms harvested at 1 month, and this rate was significantly lower in the 3-month group (10.2%, p = 0.018). The proportion of blood cells within the sac was also notably higher in the 1-month group compared with other time points. The primary tissue filling the dome at 1 month (14/15, 93%) was an unorganized thrombus primarily composed of fibrin, platelets, and red blood cells. Conversely, aneurysms harvested at 1 month had the lowest collagen level (25.6%). However, collagen became the dominant tissue component within the aneurysm sac, accounting for 71.8% of tissue in the 3-month group (p = 0.007). There were no differences observed among the examined components between the 3-month and 6-month groups. On qualitative analysis, collagen-producing SMA-positive myofibroblasts were located near or in between fibrin molecules. Healed aneurysms exhibited myofibroblasts, collagen, and a well-organized fibrin network on the aneurysm neck. In contrast, unhealed aneurysms displayed a poorly organized fibrin network with scattered myofibroblasts at the neck area. These findings indicate that fibrin plays a foundational role in the gradual occlusion of aneurysms after flow diverter treatment. Endovascular approaches that enhance fibrin accumulation could potentially improve aneurysm occlusion rates. Further research is needed to establish the precise role of fibrin in aneurysm occlusion.

An Improved Surgical Technique to Increase Neck Width of Elastase-Induced Aneurysm Model in Rabbits: A Prospective Study

BackgroundRabbit elastase-induced aneurysms have widely been used to test various endovascular materials over the past two decades. However, wide-necked aneurysms cannot be stably constructed.ObjectiveThe purpose of the study was to increase the neck width of the elastase-induced aneurysm model in rabbits via an improved surgical technique with two temporary clips.Materials and MethodsFifty-four elastase-induced aneurysms in rabbits were successfully created. Group 1 was (n = 34) composed of cases in which two temporary aneurysm clips were placed closely medially and laterally to the origin of the right common carotid artery (RCCA), respectively. Group 2 (n = 20) included cases in which a single temporary aneurysm clip was placed crossed the origin of RCCA. Digital subtraction angiography (DSA) was performed before and immediately after elastase incubation and 3 weeks later. The diameter of the origin of RCCA before and immediately after elastase incubation and aneurysm sizes of the two groups were measured and compared. Moreover, the correlation analysis was performed between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.ResultsThe mean aneurysm neck and dome width of group 1 were both significantly larger than that of group 2 (p-value < 0.001 and p-value = 0.005, respectively). Moreover, the proportion of wide-necked aneurysms (neck width ≥4 mm) in group 1 was significantly larger than that in group 2 (p-value = 0.004) and the mean dome to neck ratio (D/N) of group 1 was smaller than that of group 2 (p-value = 0.008). Furthermore, there was a positive correlation between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.ConclusionThe improved surgical technique with two temporary clips, focusing on the direct contact of elastase with the origin of RCCA, could increase the neck width of elastase-induced aneurysm models in rabbits.

Rabbit Elastase Aneurysm Model Mimics the Recurrence Rate of Human Intracranial Aneurysms following Platinum Coil Embolization.

Intracranial aneurysms treated with coils have been associated with incomplete occlusion, particularly in large or wide-neck aneurysms. This study aimed to validate the accuracy of the rabbit elastase model in predicting aneurysm recurrence in humans treated with platinum coils. Elastase-induced saccular aneurysms were induced in rabbits and embolized with conventional platinum coils. The recurrence rates of aneurysms were retrospectively analyzed. Morphologic characteristics of aneurysms, angiographic outcomes, and histologic healing were evaluated. A total of 28 (15.3%) of 183 aneurysms recurred. The aneurysm recurrence rate observed in this study (15.3%) is similar to those reported in multiple analyses of aneurysm recurrence rates in humans (7%-27%). The rate of recurrence was higher in aneurysms treated without balloon assistance (19/66, 28.8%) compared with those treated with balloon assistance (9/117, 7.7%). Aneurysms treated with balloon-assisted coiling had a lower recurrence rate (OR = 0.17; 95% CI, 0.05-0.47; P = .001) and higher occlusion rate (OR = 6.88; 95% CI, 2.58-20.37; P < .001) compared with those treated without balloon-assisted coiling. In this rabbit elastase-induced aneurysm model, packing density and aneurysm volume were weak predictors of aneurysm recurrence; however, the packing density was a good predictor of the occlusion rate (OR = 1.05; 95% CI, 1.02-1.10; P = .008). The rabbit elastase aneurysm model may mimic aneurysm recurrence rates observed in humans after platinum coil embolization. Moreover, balloon assistance and high packing densities were significant predictors of aneurysm recurrence and occlusion.

WEB Device Shape Changes in Elastase-Induced Aneurysms in Rabbits.

While WEB devices have been shown to be safe and effective for aneurysm treatment, WEB-shape modification compression has been associated with incomplete aneurysm occlusion. We explored the relationship between occlusion rates and WEB-shape modification in different WEB device types in an experimental aneurysm model. Elastase-induced aneurysms were created in rabbits and treated with dual-layer (n = 12), single-layer (n = 12), or single-layer sphere (n = 12) WEB devices. Aneurysms were followed up either at 3 or 12 months. Angiographic occlusion was graded using the WEB Occlusion Scale: grade I, complete; grade II, complete but recess filling; grade III, residual neck; or grade IV, residual aneurysm. WEB-shape modification and histologic features were also analyzed. Grade I or II occlusion was seen in 16 (44%) aneurysms, and grade I, II, or III ("adequate") occlusion was observed in 22 (61.1%) aneurysms at follow-up. WEB-shape modification was observed in 22 (61.1%) aneurysms. WEB-shape modification was higher in single-layer (9/12) and dual-layer (10/12) devices compared with single-layer sphere devices (3/12). Aneurysms with WEB-shape modification had a higher level of thrombus organization in the dome compared with those without WEB-shape modification (68% [15/22] versus 50% [7/14]). WEB-shape modification was not correlated with angiographic or histologic outcomes but was significantly correlated with levels of fibrosis and smooth muscle cells in the aneurysm. WEB-shape modification is not associated with incomplete aneurysm occlusion of WEB devices in the rabbit model but may be related to connective tissue formation and the healing response to WEB device implantation.

Adaptive Remodeling in the Elastase-induced Rabbit Aneurysms.

Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry. Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits. Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation. The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6 ± 14.3 μm. Collagen fibers in this layer were multi-directional (AI = 0.56 ± 0.15) with low tortuosity (1.08 ± 0.02) compared with adjacent circumferentially aligned medial fibers (AI = 0.78 ± 0.12) and highly tortuous adventitial fibers (1.22 ± 0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging. A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.

An Effective and Simple Way to Establish Elastase-Induced Middle Carotid Artery Fusiform Aneurysms in Rabbits.

Objective Elastase-induced aneurysms in rabbits have been proposed as a preclinical tool for device development, but there is still much deficiency in those aneurismal models. So we need to explore the efficient and convenient animal models for the investigation of intracranial aneurysms. Then, we compared and analyzed three methods of elastase-induced carotid artery aneurysms in rabbits and aimed to find a simple, effective, and reproducible method for creating elastase-induced aneurysms. Methods 42 standard feeding male adult Japanese white rabbits (3.05 ± 0.65 kg) were randomly divided into 3 groups and treated with elastase ablation to create common carotid artery (RCCA) aneurysm models: Group A (root-RCCA medication group, n = 12), Group B (mid-RCCA medication group, n = 18), and Group C (ligated RCCA+medication group, n = 12). For Group A, the origin of the RCCA was blocked by two temporary aneurysm clips, and the resulting 2 cm cavity was infused with elastase for 20 min, then the clip was removed and the RCCA was not ligated. For Group B, the middle part of RCCA was treated the same way as Group A and the RCCA was not ligated. For Group C, the middle part of RCCA was treated as Group B, but the distal RCCA was ligated. After the aneurysm models were created for 3 weeks, prior to sacrificing the animals, color Doppler ultrasound and angiography were performed for blood flow measurements inside the aneurysms. Histological analysis (such as SMA-α, CD31, CD34, CD68, collagen IV, and Ki67) and the other relevant indexes were compared between the ideal model's aneurysmal tissues and the human intracranial aneurysm's tissues to confirm whether we have successfully established elastase-induced aneurysm models. Results Compared with human intracranial aneurysm specimens by the color Doppler ultrasound, angiography, and changes in the inner diameter of arteries, all three methods have successfully established the elastase-induced aneurysm models. Histology showed that biological responses were similar to both human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Group A and Group B had the same morphology, but Group A had a higher mortality rate than Group B. Group B and Group C had different morphology. The aneurysm of Group C was more similar to human cerebral aneurysms but had a higher mortality rate than Group B. Group B was confirmed not only as an alternative method but also as a more safe and effective method for creating elastase-induced aneurysm models. Conclusion Through analysis and comparison, the Group B is proven to be the simplest, reproducible, and most effective modeling method. The aneurysm model established by Group B can be used for basic research related to aneurysm mechanism. We have provided a new and effective method for basic research on aneurysm.

Tissue-engineered aneurysm models for in vitro assessment of neurovascular devices.

Preclinical testing of neurovascular devices is crucial for successful device design and is commonly performed using in vivo organisms such as the rabbit elastase-induced aneurysm model; however, simple in vitro models may help further refine this testing paradigm. The purpose of the current work was to evaluate, and further develop, tissue-engineered blood vessel mimics (BVMs) as simple, early-stage models to assess neurovascular devices in vitro prior to animal or clinical use. The first part of this work used standard straight-vessel BVMs to evaluate flow diverters at 1, 3, and 5 days post-deployment. The second part developed custom aneurysm-shaped scaffolds to create aneurysm BVMs. Aneurysm scaffolds were characterized based on overall dimensions and microstructural features and then used for cell deposition and vessel cultivation. It was feasible to deploy flow diverters within standard BVMs and cellular linings could withstand and respond to implanted devices, with increasing cell coverage over time. This provided the motivation and foundation for the second phase of work, where methods were successfully developed to create saccular, fusiform, and blister aneurysm scaffolds using a wax molding process. Results demonstrated appropriate fiber morphology within different aneurysm shapes, consistent cell deposition, and successful cultivation of aneurysm BVMs. It is feasible to use tissue-engineered BVMs for assessing cellular responses to flow diverters, and to create custom aneurysm BVMs. This supports future use of these models for simple, early-stage in vitro testing of flow diverters and other neurovascular devices.

Rabbit aneurysm models mimic histologic wall types identified in human intracranial aneurysms

BackgroundSemiquantitative scales correlate histopathologic findings in the walls of human aneurysms with rupture status.ObjectiveTo apply a semiquantitative scale to the rabbit elastase-induced aneurysm model to determine whether rabbit histologic types...

Abstract 11: Intra-arterial Infusion of Allogeneic Mesenchymal Stem/Stromal Cells is Safe and Enhances Histological Healing in Rabbit Elastase Aneurysms

Introduction: Poor healing of coiled intracranial aneurysms results in recanalization and recurrence of the aneurysm in one in five patients. One recent study has shown that intra-arterial infusion of Mesenchymal Stem/Stromal Cells (MSCs) can stop dilation of experimental aneurysms in rabbits. Another study in a mouse model suggests that intravenous delivery of MSCs reduces the risk of aneurysm rupture. MSCs are known for their ability to establish a regenerative microenvironment by inhibiting inflammation, producing trophic factors, and recruiting local progenitors to replace lost cells. In this study, we have conducted a randomized preclinical trial to assess the potential of MSC therapy in improving the healing of coiled aneurysms. Hypothesis: Combined coiling and intra-arterial injection of 5 million allogeneic MSCs will be safe, and will result in superior histological healing of experimental elastase-induced aneurysms in rabbits at 4 weeks post-treatment. Methods: Bone marrow-derived MSCs were isolated from three rabbit donors in a serum-free fashion and were characterized individually. Elastase-induced carotid aneurysms were created in 9 New Zealand White Rabbits. Each subject was randomized to receive one of the following treatments: 1) coiling (treatment group), 2) coiling with an intra-arterial injection of saline solution (vehicle group) and coiling with an intra-arterial injection of 5 million allogeneic MSCs (treatment group). The animals were followed up for 4 weeks, at the end of which a final angiogram and histological analysis was performed. Results: Intra-arterial cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Histological results showed consistent superior healing in cell therapy group compared with vehicle and control groups. Angiographic results were not significantly different among different study arms. Conclusions: Intra-arterial MSC therapy for intracranial aneurysms is feasible, safe and effective at a proof-of-concept level.

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.

Hemodynamic analysis of fast and slow aneurysm occlusions by flow diversion in rabbits

PurposeTo assess hemodynamic differences between aneurysms that occlude rapidly and those occluding in delayed fashion after flow diversion in rabbits.MethodsThirty-six elastase-induced aneurysms in rabbits were treated with flow diverting devices....

Endothelial Progenitor Cells Contribute to Neointima Formation in Rabbit Elastase‐Induced Aneurysm after Flow Diverter Treatment

Endothelial progenitor cells (EPCs) are involved in vascular repair and homeostasis after vascular injuries. In this study, we aimed to explore whether bone marrow (BM)-derived EPCs contribute to neointima formation and reendothelialization in rabbit elastase-induced aneurysm after flow diverter treatment. Elastase-induced aneurysms were created in New Zealand male rabbits. Three weeks after model creation, flow diverter was implanted to cover the induced aneurysm neck. Autologous EPCs were isolated from bone marrow, expanded ex vivo, double labeled with Hoechst 33,342 and CFSE(carboxyfluorescein diacetate succinimidyl ester), and transplanted transvenously into the rabbits. The rabbits were assigned into three groups. The first group received autologous transfusion of double-labeled EPCs from the first day after stent implantation, and the second group received transfusion from the fifteenth day. The autologous transfusion was given at a 3-day interval and continued for 2weeks. Fluorescence-labeled cells were tracked under fluorescence microscope at the aneurysm neck and parent artery in the two groups. The third group was established as control group without EPCs transplantation. Scanning electron microscope was used to investigate the reendothelialization rate between the former two groups and the control group. In the first group, double-positive EPCs were found in 3/5 rabbits and mainly located in the subendothelial space and around the stent struts. In the second group, double-positive EPCs were found in 2/5 rabbits and mainly located on the surface of neointima. More endothelial-like cells were observed on the neointima of aneurysm neck and stented parent artery in the groups with EPCs transplantation than control group without EPCs transplantation, but the difference on the number of these cells did not reach statistical significance. BM-derived EPCs participate in neointima formation and reendothelialization in elastase-induced aneurysm after flow diverter treatment. The EPCs may differentiate into different cell types according to the stages of neointima formation in vivo.

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.

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

Creation of Bifurcation-Type Elastase-Induced Aneurysms in Rabbits

Elastase incubation was performed in the LCCA in 13 New Zealand white rabbits. Three weeks after incubation, DSA demonstrated that 10 (10/13, 77%) bifurcation-type aneurysms at the origin of the LCCA were present; mean aneurysm neck, width, and height values were 3.7 ± 1.1, 3.8 ± 0.9, and 8.7 ± 2.3 mm, respectively. The LCCA can be used to create bifurcation aneurysms in rabbits.

Correlation of aneurysm occlusion with actual metal coverage at neck after implantation of flow-diverting stent in rabbit models

A remarkable curing rate has been achieved in the treatment of intracranial intractable aneurysms by using flow-diverting stents (FDS). An appropriate metal coverage (MC) of this device influences the hemodynamics of aneurysm significantly but little to branches in vitro. The MC changes after elongation or compression and the actual changes are still unknown in vivo. In this paper, we analyzed the correlation of aneurysm occlusion with actual MC after implantation of FDS in rabbit models. FDS was implanted across the necks of 22 elastase-induced aneurysms in rabbits. Animals were performed for angiography at 4weeks and sacrificed at 3months after angiography for pathology. Tissue was explanted with stent for micro-computed tomography scan, and local shape of stent at neck was reconstructed. Actual MC at neck was calculated, and the correlations of aneurysm occlusion with effective factors were analyzed. Greater than 95% angiographic aneurysm occlusion rates for the FDS, which covered the neck of aneurysms, were 61.9% at 4weeks and 57.9% by angiography at 3months. Aneurysm occlusion was positively correlated with local MC of stent at neck (r (s) = 0.486; P = 0.026). A 35% actual MC at the neck predicted greater than 95% angiographic aneurysm occlusion with a specificity of 100% and sensitivity of 53.8%. Aneurysm occlusion was positively correlated with local MC of stent at the neck. The FDS with 35% MC can predict greater than 95% angiographic aneurysm occlusion.

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.

A Modified Technique Improved Histology Similarity to Human Intracranial Aneurysm in Rabbit Aneurysm Model

Persistent undigested elastic membranes and collagen in the tunic media of rabbit elastase-induced aneurysm models lowered their histology similarity to human intracranial aneurysm. Our purpose was to make good the deficiency. Ten New Zealand white rabbits were divided into three groups: six rabbit in two groups for evaluating the difference in various treatments, and four rabbits for long-term observation. We inflated and occluded the right common carotid artery (CCA) by an endovascular technique. The first group of three rabbits was only given 200u elastase in the proximal segment of right CCA; the second group was given 100u elastase and 1.5mg collagenase, then the right CCA was ligated. The first and second groups were studied by magnetic resonance angiography (MRA), sacrificed at three weeks after aneurysm creation, their histology results were obtained and compared with human aneurysm. The third group underwent the same procedure as the second group only for three months of observation with enhanced MRA. Saccular aneurysms formed in all rabbits. Degeneration of the extracellular matrix and atrophy of smooth muscular cells in tunic media were more apparent in the second group. The third group remained stable for more three months. Two modifications included inflating the right CCA with a balloon and adding collagenase incubation can promote an aneurysm model more histologically similar to human aneurysm. In addition the improved aneurysm model remains stability for a long time.

Sensitivity of CFD Based Hemodynamic Results in Rabbit Aneurysm Models to Idealizations in Surrounding Vasculature

Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating the role of hemodynamics in vascular diseases such as cerebral aneurysms and atherosclerosis. However, such models necessarily only include isolated segments of the vasculature. In this work, we evaluate the influence of geometric approximations in vascular anatomy on hemodynamics in elastase induced saccular aneurysms in rabbits. One representative high aspect ratio (AR-height/neck width) aneurysm and one low AR aneurysm were created at the origin of the right common carotid artery in two New Zealand white rabbits. Three-dimensional (3D) reconstructions of the aneurysm and surrounding arteries were created using 3D rotational angiographic data. Five models with varying extents of neighboring vasculature were created for both the high and low AR cases. A reference model included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies were performed and streamlines, wall shear stress (WSS), oscillatory shear index, and cross sectional velocity were compared between the models. The influence of the vascular domain on intra-aneurysmal hemodynamics varied between the low and high AR cases. For the high AR case, even a simple model including only the aneurysm, a small section of neighboring vasculature, and simple extensions captured the main features of the steamline and WSS distribution predicted by the reference model. However, the WSS distribution in the low AR case was more strongly influenced by the extent of vasculature. In particular, it was necessary to include the downstream quadrification and upstream LCCA to obtain good predictions of WSS. The findings in this work demonstrate the accuracy of CFD results can be compromised if insufficient neighboring vessels are included in studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of aspect ratio, hemodynamic parameters of interest, and acceptable magnitude of error when selecting the vascular domain will increase reliability of the results while decreasing computational time.

Five-Year Follow-Up in Elastase-Induced Aneurysms in Rabbits

There is no report regarding patency of elastase-induced aneurysms for more than a 2-year period. Our aim was to report aneurysm patency rates up to 5 years in the elastase-induced aneurysm model in rabbits. Twenty-five elastase-induced aneurysms were created in New Zealand white rabbits and followed for up to 5 years. Thirteen (52%) rabbits died during follow-up for reasons unrelated to the aneurysms. DSA was performed at 1 month and at 2 and 5 years in the 12 surviving subjects. Aneurysm patency and dimensions, including neck diameter and aneurysm width and height, were evaluated at each time point in relation to external sizing devices. Differences of aneurysm sizes (neck width and aneurysm width and height) among time points were compared by using the Student t test. Eleven (92%) of the 12 aneurysms in the subjects that survived for 5 years remained fully patent throughout follow-up. A single narrow-neck aneurysm showed partial thrombosis at the 2- and 5-year time points. Experimental elastase-induced aneurysms in rabbits demonstrate high rates of patency up to 5 years following creation. When planning for very long-term studies, investigators should plan for relatively high rates of mortality unrelated to aneurysm pathology.