Cardiac Allograft Vasculopathy: An Ongoing Challenge in the Care of Heart Transplant Recipients
Year: 2012
Type: book-chapter
Abstract: The endomyocardial biopsy has limited sensitivity in the recognition of vasculopathy because it samples only the smallest of intramyocardial arteries and arterioles, which often www.intechopen.comCardiac Transplantation 80 do not show histologic features of CAV.Reported histologic changes seen in the small arteries in endomyocardial biopsies include concentric intimal thickening with or without foamy macrophages, subendothelial accumulation of lymphocytes, and perivascular fibrosis (Pardo et al., 1997).Evidence of myocardial ischemia, such as myocytolysis, frank coagulation necrosis, and healing ischemic lesions as well as interstitial, perivascular, and replacement fibrosis can be seen (Neish et al., 1992).Identification of myocardial injury should raise the suspicion of CAV as the cause of graft dysfunction.The absence of these findings, however, does not necessarily rule out the presence of CAV. PathogenesisThe development of CAV represents a complex interaction between acute and chronic immune activation via an allo-immune pathway and alloantigen-independent non-immune mechanisms that ultimately lead to inflammation and endothelial injury, the precursor to CAV. (Figure 2).Immunologic events appear to be most important, since CAV develops in the donor's coronary arteries but not the recipient's vasculature.The donor coronary artery endothelial cells express major histocompatibility complex (MHC) class I and class II antigens, and thus appear to be primary targets of the cell-mediated and humoral immune responses.These antigens are thought to be recognized by recipient CD8+ and CD4+ T cells and these activated lymphocytes secrete cytokines (interleukins, interferons, and tumor necrosis factors), which promote proliferation and further activation of allo-reactive T cells, monocytes, and macrophages.Macrophages are then recruited to the intima where they elaborate cytokines (IL-1, IL-6, tumor necrosis factor TNF alpha) and growth factors [platelet derived growth factor (PDGF), insulin-like growth factor-I (IGF-I), transforming growth factor-alpha (TGF-alpha), TGF-beta-1], leading to smooth muscle cell proliferation and synthesis of extracellular matrix (Libby P & Tanaka H, 1994).T cell activation also stimulates the expression of adhesion molecules, [intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin] thereby "activating" endothelial cells, enabling recruitment of proinflammatory cells from the vasculature and the initiation of the immune response and subsequent development of CAV.(Briscoe et al., 1995) Pathologic characteristic CAV Native CAD Lesion morphologyDiffuse, concentric (variable) Focal, proximal, eccentric Vessels involved Intramyocardial, epicardial branchesEpicardial, spares intramyocardial branches
Source: InTech eBooks
DOI: 10.5772/27421
Authors: Brian Clarke, Kiran Khush
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W1495668676