| Background Cardiac allograft vasculopathy(CAV) is a significant obstacle to improving outcomes in heart transplant recipients. Intravascular ultrasonography, a more sensitive technique, detects intimal thickening in up to 58% of patients at 1 year posttransplant and detects CAV in 75% of patients at 3 years. The predominant feature of CAV is a diffuse,concentric fibrous intimal hyperplasia that appears along the entire length of the affected arteries. The diffuse,obliterative nature of CAV means that changes to vascular architecture are nonreversible. Once established, the only effective treatment for the condition is retransplan-tation, but it is infrequently performed because of the limited supply of suitable organs.Because of the paucity of effective therapies for CAV, attention has been directed most toward disease prevention. Although use of 3-Hydroxy-3-methyllglutaryl coenzyme A reductase inhibitors, angio-tensin-converting enzyme inhibitors or angiotensin receptor blockers, antioxidant vitamins C and E, calcium channel blocker and all-trans retinoic acid have some effects on retarding the progression of CAV, but long-term outcomes are needed to determine whether these benefits are sustainable. Because vasculopathy is the end result of both immune- and nonimmune-mediated endothelial activation that triggers smooth muscle cell proliferation, preventing its development may best be accomplished by using an immunosuppressive drug with potent antiproliferative and antimigrative effects on vascular smooth muscle cells(VSMCs). Traditionally used immunosuppressive agents such as calcineurin inhibitors (CNIs), corticosteroids, and purine biosynthesis inhibitors have hitherto shown little efficancy for preventing CAV, mycophenolate mofetil may havs some efficacy in this regard. Nevertheless, it is clear that better treatment options for prevention of CAV are required. Rapamycin (Rapa,Sirolimus) combine effective immunosuppression with antiprolife-...
|
PDF Full Text Request