Heart transplantation immunosuppression

Muromonab Orthoclone OKT 3 Prophylaxis of rejection after heart transplantation immunosuppression 1986/1992... 

Cardiomyoplasty could gready reduce the overwhelming need for heart transplants. It might also eliminate the need for immunosuppressive dmgs. 

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

APCs, antigen-producing cells MMF, mycophenolate mofetil OKT-3, muronomab-CD3. (Adapted from Mueller XM. Drug immunosuppressive therapy for adult heart transplantation I. Immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 2004 77 354-362, with permission.)... 

Until his death in September 2007, Brano continued to make invaluable contributions to the field of heart transplantation, particularly immunosuppression... 

Mycophenolic acid (MPA) was isolated from cultures of Penicillium spp. in 1896 and was purified in 1913. Initially the compound was studied for its antifungal and antibacterial effects and later for its antitumor effects. Many years later, its immunosuppressive activities were recognized and after further developmental work, an ester prodrug mycophenolate mofetil was developed, which was approved by the United States Food and Drug Administration for the prevention of acute renal allograft rejection in 1995 and for heart transplant recipients in 1998. Mycophenolate mofetil is a cytotoxic agent now used for immunosuppressive therapy and is the mofetil ester of MPA, which is the active immunosuppressive agent. 

A 59-year-old woman taking pravastatin 20 mg/day tolerated immunosuppression with ciclosporin, prednisone, and mycophenolate mofetil for 4 years after heart transplantation. After switching from pravastatin to simvastatin she developed severe muscle weakness and laboratory evidence of muscle breakdown. The biochemical markers of rhabdomyolysis did not normalize until after repeat hemodialysis. Clinical improvement did not occur until after 5 months. 

Organ transplant Immunosuppression Transplantation of liver, kidney, heart, and so forth... 

Mycophenolic acid (Figure 3.36) is produced by fermentation cultures of the fungus Penicillium brevicompactum. It has been known for many years to have antibacterial, antifungal, antiviral, and antitumour properties. It has recently been introduced into medicine as an immunosuppressant drug, to reduce the incidence of rejection of transplanted organs, particularly kidney and heart transplants. It is formulated as the /V-morpholinoethyl ester mycophenolate mofetil (Figure 3.37), which is metabolized after ingestion to mycophenolic... 

Toxicities are numerous and frequently include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, and hirsutism. A significant increase in the incidence of cholelithiasis has been observed in children treated with cyclosporine after heart transplantation. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) has been documented in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because it induces TGF-3, which promotes tumor invasion and metastasis. 

Tange S, Scherer MN, Graeb C, et al. The antineoplastic drug paclitaxel has immunosuppressive properties that can effectively promote allograft survival in a rat heart transplant model. Transplantation 2002 73(2) 216-223. 

A 30-year-old male has had a heart transplant and is being maintained on the immunosuppressant, cyclosporine. He develops a Candida infection and is treated with ketoconazole. Why is this poor therapy ... 

Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Geiran O, Fauchald P, Simonsen S. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999 40(2 Pt 1) 177-86. 

Brann WM, Bennett LE, Keck BM, Hosenpud JD. Morbidity, functional status, and Immunosuppressive therapy after heart transplantation an analysis of the joint international Society for Heart and LungTransplantation/United Network for Organ Sharing Thoracic Registry. J Heart Lung Transplant 1998 17 374-382. 

Cyclosporine was approved for transplant immunosuppression in 1983. It is administered to prevent organ rejection after transplant of kidney, liver, lung, heart, or bone marrow. In addition, it has been given to patients with nephrotic syndrome, rheumatoid arthritis, psoriasis, severe Crohn s disease, and for other medical conditions. 

Xie HG (2010) Personalized immunosuppressive therapy in pediatric heart transplantation progress, pitfalls and promises. Pharmacol Ther 126 146-158... 

Irving CA, Webber SA (2010) Immunosuppressive therapy for pediatric heart transplantation. Curr Treat Options Cardiovasc Med 12 489-502... 

Dengler TJ, Strnad N, Buhring I, et al. Differential immune response to influenza and pneumococcal vaccination in immunosuppressed patients after heart transplantation. Transplantation 1998 66 1340-1347. 

Data are also available for MS patients, where supplementation with 25(OH)2D3 increased serum levels of antiinflammatory cytokine TGF-J3 after 6 months of treatment, whereas no or little effect was observed on TNF-a, IL-13, IFN-y and IL-2 [187]. No information was given on the clinical presentation of these patients after treatment. In type I diabetes, a long-term study proved dietary vitamin D supplementation was clinically beneficial in terms of reduced risk of the disease [165]. Heart transplant recipients that were treated with low-dose l,25(OH)2D3 aiming at reduction of bone loss required significantly less cyclosporin for prevention of organ rejection suggesting a potentially beneficial immunosuppressive role of l,25(OH)2D3 in transplantational medicine [188]. 

Briffa, N.K. et al. (2003) Reduction of immunosuppressant therapy requirement in heart transplantation by calcitriol. Transplantation, 75, 2133-2134. 

In 1989 tacrolimus (FK 506), a second caldneurin inhibitor started its clinical journey [8]. Tacrolimus has an immunosuppressive effect approximately 100 times more potent than CsA and early clinical trials demonstrate that FK 506 was effective in reversing refractory acute rejection in renal, liver and heart transplantation. Subsequently, this drug showed to be at least as effective as CsA in the primary immunosuppression schedules for solid organ and bone marrow transplantation and, similarly to CsA, proved to be a valuable alternative in the treatment of autoimmune diseases [3,9-11]. At the moment, FK 506 is considered the only drug that can substitute CsA in primary immunosuppression schedules and it is currently used in almost 60% of liver transplantation immunosuppressive prescriptions. 

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