Allograft conduit wall calcification in a model of chronic arterial graft rejection.
Early allograft vascular wall degeneration has emerged as a major important complication in young patients. To explain this mechanism, we reviewed studies on explants of allograft valved conduits implanted heterotopically into the infrarenal aorta in inbred rats (LEW; RT1I and CAP-RT1C). The following strain combinations (isografts and allografts) were used: syngeneic, LEW- > LEW, strongly allogeneic, and CAP > LEW (RT1- and non-RT1-incompatible). Second-set skin grafting was performed 3 weeks after the heterotrophic implant to test for immunogenicity and presensitization. The animals (LEW) were sacrificed serially on days 20, 30, 50, and 100 for immunofluorescence and SEM studies. Endothelial disruption was observed on day 30, while valve leaflets appeared 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 smooth muscle cells was also observed in both viable and allovital grafts. Allovital grafts demonstrated more disorganized collagen and elastic 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 walls of allovital conduits calcified earlier 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 calcific degeneration in allograft vascular conduits.
Yankah
A C
AC
German Heart Institute Berlin, Germany.
Wottge
H U
HU
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D001012:Aorta, Abdominal / Q000473:pathology / Q000601:surgery; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000209:etiology* / Q000473:pathology; D006084:Graft Rejection / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G