Cardiac transplantation and diseaseSirolimus therapy in cardiac transplantation
Section snippets
Prevention of acute heart allograft rejection
The efficiency of de novo rapamycin therapy in preventing acute allograft rejection in human heart transplant recipients was first tested in a pilot clinical trial in 2001.11 Eleven heart transplant recipients received an initial rapamycin loading dose of 10 to 15 mg followed by a daily dose of 10 mg up to a target plasma level of 10 ng/mL. All patients were treated with a standard prednisone regimen, and eight also received basilixicimab (20 mg) on postoperative days 1 and 4. On average,
Treatment of refractory acute allograft rejection
Rapamycin therapy has been proposed by some as a useful adjunct in the treatment of acute allograft rejection that is not reversible with a standard treatment regimen. The rationale for this is that (a) rapamycin in vitro displays an immunosuppressive potency 10 to 100 times greater than that of calcineurin inhibitors13; (b) rapamycin and calcineurin inhibitors have different sites of action2; and (c) rapamycin appears to be less nephrotoxic than calcineurin inhibitors.11 In animal models,
Induction of transplantation tolerance
Although advances in immunosuppressive therapy have led to improved posttransplantation survival, the central long-term aim of posttransplantation therapy remains transplantation tolerance. The most critical mechanism of transplantation tolerance is depletion of antigen-activated T cells.20 Therefore, drugs that interfere with the death of activated T cells (eg, cyclosporine) can inhibit tolerance, whereas drugs that induce their death can promote it. When not dividing, T cells become
Prevention and treatment of cardiac allograft vasculopathy
Because mTOR is widely distributed among signaling pathways in many tissues, the antiproliferative effects of rapamycin are not limited to lymphoid cells. Blockade of mTOR by rapamycin results in inhibition of cell cycle in several tissue types, including endothelial, fat, myocardial, skeletal muscle, macrophage, fibroblast, pancreatic, hepatic, bone marrow, and kidney cells.24
Because the growth and migration of vascular smooth muscle cells are important for neointimal proliferation after
Conclusions
Rapamycin can effectively prevent acute graft rejection and inhibit refractory acute graft rejection in heart transplant recipients by exerting potent immunosuppressive and antiproliferative effects without adversely affecting renal function. This supports the use of rapamycin therapy in heart transplant recipients. especially in those with renal dysfunction, for whom treatment with calcineurin inhibitors is contraindicated. Rapamycin may also halt and even reverse the progression of cardiac
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Cited by (23)
Impact on Renal Function of the Use of Sirolimus in Cardiac Transplantation
2007, Transplantation ProceedingsCitation Excerpt :In the other patients, renal function (valued according to the creatinine and urea levels) was stable without needing to establish extra-renal purification techniques. Other authors have observed these findings.8 The difference observed between the average level of creatinine of patients with CRF who needed hemodialysis and those who did not need it was close.
Sirolimus-induced Alveolar Hemorrhage
2007, Journal of Heart and Lung TransplantationCardiac transplant experience with cyclosporine
2004, Transplantation ProceedingsImmunosuppression, diagnosis, and treatment of cardiac allograft rejection
2004, Seminars in Thoracic and Cardiovascular SurgeryTransplantation for end-stage heart disease
2016, Management of Heart Failure: Volume 2: Surgical, Second Edition