The continuing challenge of cardiac transplant arteriosclerosis.
Coronary arteriosclerosis of the graft, a manifestation of CAV, continues to limit the long-term success of cardiac transplantation. It is characterized by vascular injury induced by a variety of noxious stimuli, including the humoral and cellular immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classical risk factors. The proliferative and obstructive vascular lesions are thought to develop through repetitive endothelial injury followed by repair response. T lymphocytes, macrophages and neutrophils migrate to the subendothelial area via the activity of endothelial adhesion molecules, and, in turn, produce various cytokines and growth factors which cause progression of the process. Development of anti-endothelial antibodies may progress CAV in specific settings. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern of intimal proliferation observed in distal segments. In addition to the morphological alterations, functional endothelial and smooth muscle cell alterations may occur independently and transiently. The use of cyclosporine A levels > 3 mg/kg/day, HMG-CoA-reductase inhibitors and calcium antagonists has been shown to decrease the progression of CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules, cytokines and antiendothelial antibodies, as well as, antiproliferative drugs, methods to augment endogenous nitric oxide bioavailability and newer immunosuppressive regimens may be protective to endothelial injury and subsequent development of CAV. Revascularization procedures have an established, but very limited role in the setting of significant focal lesions. The ethical dilemma surrounding retransplantation, however, is considerable because of the scarcity of donor hearts.
Weis
M
M
Medizinische Klinik und Poliklinik I, University Hospital Grosshadern, Munich, Germany.
Meiser
B M
BM
Reichart
B
B
von Scheidt
W
W
D000818:Animals; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D012086:Reoperation; D012307:Risk Factors; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents