Healing mechanisms in experimental aneurysms I. Vascular smooth muscle cells and neointima formation

Purpose The purpose of this work is to better define healing phenomena in this mode l, in an effort to find strategies to improve long term results of endovasc ular treatment. Methods Lateral wall venous pouch aneurysms were constructed on both carotid arteri es in 30 pigs. The aneurysms were packed with collagen sponges per-operativ ely in 25 animals. Angiography, serial histological studies and immune-hist ochemistry tests were used to study healing phenomena and measure neontima formation at various time intervals from 1 day to 9 weeks after surgery. GD C embolization was performed in 5 other pigs for comparison with the collag en sponge model. Explants from the neointima at the neck of aneurysms as we ll as from the parent artery of 8 pigs were prepared in an attempt to grow and to characterize in vitro cells responsible for healing porcine aneurysm s using immunocytochemistry and enzymatic assays. To confirm the hypothesis that an analogy exists between cells involved in aneurysmal healing and ne ointimal cells found in restenosis, explant outgrowths were scored and comp ared to explants from intact carotid arteries and carotid arteries subjecte d to angioplasty in 3 other animals. In addition, to test the value of neoi ntima measurements in quantifying results, 6 dogs were analysed to correlat e the thickness of the neointima formed at the neck of aneurysms with angio graphic results in animals prone to recurrences. Results Histopathological findings with collagen sponge packing were similar to the ones following coil embolization. Porcine aneurysms had a strong tendency to heal with a thick neointima primarily composed of vascular smooth muscle cells (VSMCs). Aneurysms in dogs did not heal as well and the neointima at the neck of treated lesions was thin. Cells responsible for healing of exp erimental porcine aneurysms could be cultured in vitro, and are activated V SMCs. These cells, similar to those harvested following balloon injury, had a higher colony forming capacity and an accelerated explant outgrowth rate as compared to cells derived from the parent artery. Conclusion Animals which heal poorly harbor a thin or deficient neointima at the neck of treated aneurysms. Favorable healing in porcine aneurysms involves VSMCs which form a thick neointima. These VSMCs can be cultured in vitro. They s hare similar outgrowth characteristics with VSMCs recovered after balloon a ngioplasty. The collagen sponge model may be useful to harvest cells for in vitro experimentation and in the in vivo evaluation of the local delivery of potential therapeutic molecules thought to improve healing following emb olization of aneurysms.