Citations

Background Animal models are essential for evaluating endovascular device safety and efficacy. Rats offer advantages, such as genetic manipulability, lower cost, and shorter healing and breeding cycles, compared to large animals. These features support studying aneurysm healing mechanisms and enable high-throughput testing. We developed an optimal rat aneurysm model for device evaluation. Methods Saccular aneurysms were created at the origins of the left renal artery (LRA) with acetylsalicylic acid (ASA) (LRA/ASA group, n = 7); the right common iliac artery (RCIA) with ASA alone (RCIA/ASA group, n = 6) or ASA plus clopidogrel (CLP) (RCIA/ASA + CLP group, n = 7); and the left common iliac artery (LCIA) with ASA + CLP (LCIA/ASA + CLP group, n = 7). The origins of these arteries were surgically exposed. During temporary ligation of the vessel origin, the vessel was bisected and endoluminal elastase was incubated in the proximal stump for 10 min, followed by release of the proximal ligation and permanent ligation of the stump. Angiographical and histological analysis were performed 4 weeks post-procedure. Results Follow-up digital subtraction angiography revealed mean ± standard deviation aneurysm height/neck dimensions of 1.2 ± 0.4/1.2 ± 0.1, 2.9/3.1, 2.3 ± 0.6/1.9 ± 0.3, and 2.1 ± 0.6/2.0 ± 0.4 mm for the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. The survival rate was 29%, 17%, 71%, and 86% in the LRA/ASA, RCIA/ASA, RCIA/ASA + CLP, and LCIA/ASA + CLP groups, respectively. Histopathological analysis of these aneurysms confirmed the absence of the internal elastic lamina and revealed aneurysmal changes in the arterial wall, resembling the pathological findings observed in human aneurysm specimens. Conclusions Common iliac aneurysm models with ASA + CLP can be used to evaluate the safety and efficacy of endovascular devices.

Purpose Large aneurysms have a higher rupture risk, yet no available in vivo animal model consistently produces large aneurysms for testing endovascular therapies. Recent research suggests that adding calcium chloride (CaCl 2 ) to elastase yields larger aneurysms in a surgical rabbit model. We evaluated whether this effect translates to an endovascular approach by comparing aneurysm sizes created using elastase alone versus a CaCl 2 –elastase combination. Methods Aneurysms were created in the right common carotid artery of New Zealand rabbits. One group received 1 mL porcine elastase; the other received elastase plus 0.055 g CaCl 2 (0.5 M). After four weeks, patency was confirmed via digital subtraction angiography. Two blinded co-authors measured the neck, width, and height of the aneurysms. Aneurysm volumes were estimated using AngioCalc.com. Statistical analyses were performed using either the Mann–Whitney U -test or t -test based on data distribution. Results Twenty-nine (29) New Zealand rabbits were included in the study: six in the CaCl 2 and elastase groups, 23 in the elastase-alone group. All induced aneurysms remained patent at follow-up. Mean neck size was significantly larger in the CaCl 2 + elastase group than in the elastase-alone group (4.4 ± 1.1 mm vs 3.5 ± 0.95 mm; respectively, p = 0.02). Differences in width (4.1 ± 0.92 mm vs 3.4 ± 0.36 mm; p = 0.06), height (9.0 ± 1.1 mm vs 9.1 ± 2.1 mm; p = 0.46), and volume (83.5 ± 38.35 mm ³ vs 53.0 ± 16.94 mm³; p = 0.11) were not significant between CaCl 2 + elastase and elastase-alone, respectively. Conclusions CaCl 2 modestly increased neck size but did not significantly enlarge overall aneurysm dimensions. Further studies are needed to assess its utility in endovascular aneurysm models.

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

The New Zealand rabbit elastase-induced arterial aneurysm of the right common carotid artery remains a widely used model for assessing the effectiveness and safety of new neuroendovascular devices.1 This model offers a simple and reliable platform for pre-clinical in vivo investigations, crucial for comprehending the biological processes underlying aneurysm healing after endovascular treatment.2 Notably, the induced aneurysm exhibits morphological, hemodynamic, and histological characteristics similar to human intracranial aneurysms. The creation of the aneurysm is performed using open and endovascular techniques. Each step of the procedure requires a meticulous and controlled gesture to ensure reproducibility of the aneurysm and minimize animal misuse. In video 1 we present a step-by-step procedural guide for aneurysm creation and follow-up. We hope this resource will help in promoting this model and provide useful guidance for researchers in the field. Video 1 Surgical procedure of creating elastase-induced aneurysms in rabbits.

Introduction: Numerous endovascular tools exist for the treatment of intracranial aneurysms with an increased use of flow-diverting devices in recent years. However, the biological mechanisms leading to aneurysm healing or potential complications such as delayed aneurysm ruptures after flow-diverter treatment are not yet well established. We used RNA-sequencing technology to identify genes relevant for biological impact of coils and flow-diverters in elastase-induced saccular aneurysms in rabbits and to identify genes and pathways of potential clinical interest. Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery. Aneurysms were treated with coils (n=5) or flow-diverters (Pipeline Embolic Device, Covidien, CA) (n=4). Untreated aneurysms (n=6) were used as controls. Messenger RNA and microRNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology. RNA-seq results were analyzed by using the Ingenuity Pathway Analysis tool. Results: Using RNA sequencing for coiled versus non-treated aneurysms, 464 genes were found to be differentially expressed with 58 genes down regulated and 406 genes up regulated. Using the same criteria for the flow-diverter treated aneurysms, 177 genes were found to be differentially expressed with 8 genes down regulated and 169 genes up regulated. Comparing coiled versus flow-diverter treated aneurysms, 13 genes were significantly differentially expressed with 8 down regulated and 5 up regulated genes. Genes identified with the highest interest for aneurysms healing were fibroblast growth factor-23, matrix metalloproteinases (MMP)-1, Scinderin and Basigin (implicated in MMP-2 and MMP-9 regulation). Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions. Conclusions: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and cellular migration that could explain the different biological mechanisms implicated in aneurysms healing either after coiling or flow-diverter treatments and could explain potential device-related complications.

Background Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model. Methods FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH. Results Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively). Conclusion These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.

Abstract Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion (n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.

Background To develop a preclinical thromboembolic occlusion model for studying revascularization strategies. Methods Clot analog with barium sulfate was injected into the distal aorta in 9 New Zealand white rabbits. The situation of aorta occlusion was compared among fibrin-rich (n=4), red blood cell (RBC)-rich (n=3), and whole blood clot analogs (n=2) using digital subtraction angiography. Arterial geometries, histologic features and circumferential stretch of the distal aorta in rabbits were compared with the common carotid artery in swine and the distal internal carotid artery (ICA) in humans. Aspiration thrombectomy and mechanical thrombectomy using a stent retriever were performed in two rabbits. Results The aortic bifurcation was occluded after a single delivery of clot in 4 cases. It was occluded after the second clot injection in the 5 remaining rabbits. Fragmentation of RBC-rich clots occurred during clot injection in 2 cases. The mean diameters of the distal aorta and right common iliac artery in rabbits were 3.7±0.4 and 2.8±0.3 mm, respectively; the mean diameters of human ICA, and first and second segments of the middle cerebral artery (M1, M2) were 3.6±0.4, 3.1±0.4, and 2.4±0.4 mm, respectively. Arterial revascularization was achieved in both rabbits. Geometric, mechanical and histological factors of the distal aorta in rabbit were more close to human distal ICA than swine carotid artery. Conclusion Arterial occlusion can be achieved at the aortic bifurcation in rabbits, which is comparable to human ICA bifurcation. This thrombectomy model has the potential to be used for testing of thrombectomy devices.

AbstractEmbolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold‐standard procedure, but it is time‐consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert–Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.