Rejection and repair of endothelium in major vessel transplants.
Fresh saphenous vein homografts are gaining popularity as conduits for femoral-popliteal or distal bypass grafts. Aside from major blood group compatibility, there is little clinical evidence that rejection is a significant factor in long-term patency. Some have suggested that blood vessels are weakly antigenic and others indicate that rejection does not endanger long-term patency. Transplantation and toxic damage were produced in experimental animals in order to compare healing processes. Both types of injuries produced early significant endothelial cell proliferation detected by H3-thymidine uptake. This response peaked at 5 days in transplants and ever-expanding islands of proliferating endothelium were present in aortas exposed to 20 percent sodium chloride, leading to healing in 3 to 4 months. In the transplanted vessels, total endothelial destruction occurred at 11 to 28 days, and cells of host origin determined by sex chromatin analysis gradually resurfaced those grafts that maintained patency. At 4 months only two of six carotid artery homografts were patent in unmodified dogs, and eight of nine were patent in animals given 1 mg. per kilogram of Imuran. All patent grafts were resurfaced by host cells. We conclude that rejection does play a role in long-term patency; that donor endothelium of living vascular grafts cannot maintain sufficient proliferative capacity to repair immunological damage; that small doses of Imuran significantly alter the rate of destruction leading to more orderly repair and patency; and that clinical trials utilizing one half the dose of Imuran required for kidney graft survival are likely to improve significantly the long-term patency rate of fresh arterial or venous homografts in man.
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure; D001158:Arteries / Q000637:transplantation*; D001379:Azathioprine / Q000494:pharmacology; D002339:Carotid Arteries / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D004727:Endothelium / Q000648:ultrastructure; D006084:Graft Rejection / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000187:drug effects
D004247:DNA; D001379:Azathioprine