AbstractsBiology & Animal Science

Inflammation and mechanical injury as possible reasons for chronic graft failure

by Luise Kraas




Institution: Freie Universität Berlin
Department:
Degree: PhD
Year: 2014
Record ID: 1098805
Full text PDF: http://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000097261


Abstract

Abdominal and thoracic aneurysms have a rising prevalence due to demographic changes. Patients undergoing elective surgery often present with multiple comorbidities. Endovascular aneurysm repair using stent grafts is an attractive, minimally invasive, alternative to conventional open repair but regular radiological surveillance is necessary since long-term stent graft failure can occur years after implantation. Objectives: Test the safety and biocompatibility of a chrome-cobalt custom made stent graft at 6 months implantation in the thoracic and abdominal sheep aorta. Methods: Stent grafts were analyzed radiologically and macroscopically for patency, stenosis and migration in situ. Microscopic cross sections were stained with hematoxylin-eosin, Weigert hematoxylin-phloxine-saffron and immunohistochemically for CD3+ T-lymphocytes to assess the chronic foreign body reaction, neointima formation, media atrophy, angiogenesis and inflammatory reaction. Results: Radiologic and macroscopic evaluation showed no significant changes such as endoleakage, migration or occlusion and found only slight scalloping. Microscopy analysis showed significant neointima hyperplasia (mean± SD) in the abdominal (intima: 19.5 ±9.3 µm vs. neointima: 347.8 ±212.8) and the thoracic aorta (intima: 16.3 ±8.7 µm vs. neointima 359 ±117.8 µm) and a significant media reduction in the abdominal (352 ± 85 µm) and thoracic (1453± 519 µm) parts bearing the stent graft when compared to non-stented controls from the same sheep (abdominal: 581 ± 181 µm; thoracic: 2205± 391µm). Trend analysis showed that media changes could correlate with a higher rupture score, changes in the media lamella unit structure and higher CD3+ cell counts, while neointima hyperplasia could correlate with angiogenesis but not rupture. Interestingly, the inflammatory reaction pattern depended more on the animal-specific, healthy intima and media thickness than on the stent diameter or stent/ vessel ratio. This might demonstrate the importance of genetic and developmental factors on inflammatory response in every individual after stent grafting. In addition, all stents showed multinucleated foreign body giant cell granulomas and secondary Langhans-type granulomas covering the stent surface, demonstrating an ongoing, chronic inflammation driven by innate and adaptive immunity. This aortic animal model evaluated the safety and biocompatibility of a long-term chrome-cobalt stent graft and identified chronic inflammation of the foreign body type and atrophic media rupture due to chronic mechanical injury as the main risk factors for long-term stent failure. Die weltweite Prävalenz des abdominellen und thorakalen Aortenaneurysmas steigt durch zunehmendem demographischen Wandel sowie Veränderungen des Lebensstiles. Die betroffenen Patienten haben häufig mehrere Komorbiditäten und die endovaskuläre Aneurysmentherapie stellt daher eine attraktive, weil minimal invasive, Therapiealternative zur elektiven Laparotomie oder Thorakotomie dar. Allerdings ist eine regelmäßige…