RESUMEN
BACKGROUND AND PURPOSE: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. METHODS: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. RESULTS: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P=0.008). CONCLUSIONS: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.
Asunto(s)
Aneurisma de la Aorta Abdominal/terapia , Neointima/patología , Stents , Animales , Aneurisma de la Aorta Abdominal/patología , Arterias/patología , Implantación de Prótesis Vascular , Movimiento Celular , Embolización Terapéutica , Procedimientos Endovasculares , Proteínas Fluorescentes Verdes/metabolismo , Aneurisma Intracraneal/terapia , Masculino , Neointima/terapia , Ratas , Ratas Endogámicas Lew , Trombosis/patologíaRESUMEN
BACKGROUND: Advances in stent-assisted coiling have incrementally expanded endovascular treatment options for complex cerebral aneurysms. After successful coil consolidation and aneurysm occlusion, endovascular scaffolds are no longer needed. Thus, bioresorbable stents that disappear after aneurysm healing could avoid future risks of in-stent thrombosis and the need for lifelong antiplatelet therapy. OBJECTIVE: To assess the applicability and compatibility of a bioresorbable magnesium- alloy stent (brMAS) for assisted coiling. METHODS: Saccular sidewall aneurysms were created in 84 male Wistar rats and treated with brMAS alone, brMAS + aspirin, or brMAS + coils + aspirin. Control groups included no treatment (natural course), solely aspirin treatment, or conventional cobalt-chromium stent + coils + aspirin treatment. After 1 and 4 weeks, aneurysm specimens were harvested and macroscopically, histologically, and molecularly examined for healing, parent artery perfusion status, and inflammatory reactions. Stent degradation was monitored for up to 6 months with micro-computed and optical coherence tomography. RESULTS: Aneurysms treated with brMAS showed advanced healing, neointima formation, and subsequent stent degradation. Additional administration of aspirin sustained aneurysm healing while reducing stent-induced intraluminal and periadventitial inflammatory responses. No negative interaction was detected between platinum coils and brMAS. Progressive brMAS degradation was confirmed. CONCLUSIONS: brMAS induced appropriate healing in this sidewall aneurysm model. The concept of using bioresorbable materials to promote complete aneurysm healing and subsequent stent degradation seems promising. These results should encourage further device refinements and clinical evaluation of this treatment strategy for cerebrovascular aneurysms.
Asunto(s)
Implantes Absorbibles , Aneurisma Intracraneal/terapia , Stents , Implantes Absorbibles/normas , Animales , Aspirina/administración & dosificación , Embolización Terapéutica/métodos , Estudios de Factibilidad , Aneurisma Intracraneal/diagnóstico por imagen , Masculino , Ratas , Ratas Wistar , Stents/normas , Resultado del TratamientoRESUMEN
BACKGROUND: Experimental studies to assess aneurysm occlusion or perfusion typically rely on macroscopic examination or histological analysis but cannot assess dynamic perfusion. OBJECTIVE: To describe an easy-to-implement and inexpensive fluorescence angiographic technique for the in vivo assessment and imaging of the dynamic perfusion status of aneurysms and their underlying blood vessels in a rat model. METHODS: In a rat sidewall aneurysm model, the angiographic setup included 2 bandpass filters, a video camera, and a bicycle spotlight. After 48 rats underwent fluorescein angiography, dissections were performed to confirm the perfusion status by macroscopic and histologic examination of the aneurysm. RESULTS: Direct injection of 0.2 mL fluorescein 10% Faure achieved strong, clear visibility in all 48 aneurysms. Macro-/microscopic examination identified residual perfusion in 25 and complete healing in 23 aneurysms. Fluorescein imaging identified 21 of these 25 aneurysms (84%) with residual perfusion and 22 of 23 aneurysms (96%) with no residual perfusion. CONCLUSION: Our fluorescein imaging technique proved efficient for the evaluation of aneurysm patency and parent artery integrity in this experimental setting. Fluorescein is nontoxic, can be re-administered if needed, and, in this technique, can expand the armamentarium for the preclinical evaluation of dynamic perfusion status.