Enhanced neointimal growth in cultured rabbit aorta following in vivo balloon angioplasty

We have used in vivo balloon catheterization in combination with in vitro o rgan culture to develop a model system for vascular neointima formation. A Fogarty balloon catheter was used to deendothelialize and rupture the inter nal elastic lamina of aortae in adult rabbits. After three d of recovery, a ortae were harvested, divided into segments, and placed into organ culture. We obtained a daily index of cell proliferation in cultured vessels using [H-3]thymidine incorporation into DNA. Also, segments were collected and pr ocessed for routine histology or immunohistochemistry. Aortic segments that had undergone ballooning 3 d before harvest and then cultured exhibited di ffuse neointimal growth after several d in vitro, whereas those from sham-o perated (nonballooned) rabbits showed generally only a single endothelial c ell layer that is characteristic of normal intima. Aortae that were harvest ed, balloon-damaged in vitro, and then cultured exhibited no neointimal gro wth. The neointima that developed in cultured segments from in vivo balloon ed rabbits was primarily of smooth muscle cell origin as determined by posi tive immunostaining for or-smooth muscle actin. The intima:media thickness ratios were significantly higher in aortic segments from ballooned rabbits at harvest and after 4 or 7 d in culture compared with those from nonballoo ned rabbits. Also, the [H-3]thymidine index was higher in the in vivo ballo oned aorta compared to non-ballooned or in vitro ballooned vessel. We concl ude that ballooning in vivo followed by exposure to blood-borne elements pr oduces an enhanced proliferative response in cultured vessels that is disti nct from other in vitro models of neointimal growth.