GRAFT CORONARY-DISEASE - OLD AND NEW DIMENSIONS

This article reviews briefly the histopathologic description of the le sions and the new research thrusts in the etiology of graft coronary d isease. There are now over 36,000 cardiac allografts (including those of combined heart-lung) worldwide. Immunosuppressive management has mo dulated acute rejection. However, graft coronary vascular disease (GCD ) is the major cause of death or retransplantation after the first pos toperative year. Graft coronary disease is seen as early as 3 months o r as late as 21 years posttransplant. Infants, children, and adults ar e affected. The pathology of GCD can affect all the major coronary ves sels along their entire length. including major branches and intramyoc ardial vessels. The characteristic lesion is that of concentric intima l proliferation eventually blocking the entire lumen; smaller diameter vessels may be blocked entirely before the larger epicardial vessels. Angioplasty and coronary artery bypass surgery is therefore not optim al. The intimal proliferation is due mainly to transmigration and tran sformation of smooth muscle cells through small gaps in the internal e lastic membrane. Recent studies have outlined vascular endothelial cel l activation of various kinds (triggered by rejection and other proces ses), including cytokines, growth factors, extracellular matrix protei ns, adhesion molecules, and mediators such as interleukin-1 (IL-1), in terleukin-2 (IL-2), platelet-derived growth factor (PDGF), tumor growt h factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha). Cellular and humoral rejection mechanisms also are likely involved. N onimmunologic factors contributing to GCD include hyperlipidemia, diab etes mellitus, cytomegaloviral (CMV) infection, as well as prolonged i schemic time when harvesting the heart. So far, many of these etiologi c studies have produced variable and sometimes conflicting results, an d none are conclusive. Future goals in the study of GCD include improv ed ischemic protection, more target-selective immunosuppression, block ing of vascular activation pathways, and the development of graft tole rance and even xenografting. More research in this discouraging aspect of cardiac transplantation is required. (C) 1997 by Elsevier Science Inc.