ALLOGRAFT CONDUIT WALL CALCIFICATION IN A MODEL OF CHRONIC ARTERIAL GRAFT-REJECTION

Early allograft vascular wall degeneration has emerged as a major impo rtant complication in young patients. To explain this mechanism, we re viewed studies on explants of allograft valved conduits implanted hete rotopically into the infrarenal aorta in inbred rats (LEW; RT1(1), and CAP-RT1(C)). The following strain combinations (isografts and allogra fts) were used: syngeneic, LEW-> LEW, strongly allogeneic, and CAP > L EW (RT1- and non-RT1-incompatible). Second-set skin grafting was perfo rmed 3 weeks after the heterotrophic implant to test for immunogenicit y and presensitization. The animals (LEW) were sacrificed serially an days 20, 30, 50, and 100 for immunofluorescence and SEM studies. Endot helial disruption was observed on day 30, while valve leaflets appeare d normal. Humoral allograft rejection was demonstrated and associated with production of antibodies (IgG) against the endothelial cells and around the smooth muscle cells, and in areas of smooth cell necrosis, through 100 days. Neointimal repopulation by host cells and migrated s mooth muscle cells was also observed in both viable and allovital graf ts. Allovital grafts demonstrated more disorganized collagen and elast ic fibers, as well as calcific degeneration in the media and neointima on day 50; the viable conduits showed such structural changes on day 100. In conclusion, vascular wails of allovital conduits calcified ear lier than the viable conduits without discernible calcification of the valves. There is therefore evidence to prove causative relationships between cellular viability, immune response, and fibroproliferative ca lcific degeneration in allograft vascular conduits.