Heart allograft rejection

C24. Chollet Martin, S., Depoix, J. P., Hvass, U., Pansard, Y., Vissuzaine, C., and Gougerot Pocidalo, M. A. Raised plasma levels of tumor necrosis factor in heart allograft rejection. Transplant. Proc. 22, 283-286 (1990). 

Zerwes, H.-G., Kovarik, J., Streiff M., Pally, C., Bruns, C., Beerli, C., Lewis, I., Biinteli, R. et al. (2006) Potent pharmacologic inhibitors of CXCR3 do not inhibit rat heart allograft rejection. American Journal of Transplantation, 6 (Supplement 2), 599. 

Among the pyrrole-containing natnral products and therapeutics, PNU-156804 559 expresses promising activity in the suppression of heart allograft rejection [216], and BE18591 561 do so against tnmors [217] (Fig. 13.2). 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Neuringer IP, Chalermskulrat W, Aris R. Obliterative bronchiolitis or chronic lung allograft rejection a basic science review. J Heart Lung Transplant 2005 24 3-19. 

Lancaster, J. R., Jr., Langrehr, J. M., Bergonia, H. A., Murase, N., Simmons, R. L., and Hoffman, R. A. (1992). EPR detection of heme and nonheme iron-containing protein nitrosylation by nitric oxide during rejection of rat heart allograft. J. Biol. Chem. 267, 10994-10998. 

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. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Schofield RS, Hill JA, McGinn CJ, Aranda JM. Hormone therapy in men and risk of cardiac allograft rejection. J Heart Lung Transplant 2002 21(4) 493-5. 

Prolongs the survival rate of transplanted hearts using a model of cardiac allograft rejection in mice [142]... 

Muromonab-CD3 Orthoclone OKT 3 (Ortho Biotech) Acute allograft rejection in renal transplant patients heart and liver transplant rejection... 

Murnmonab-CD3 blocks the function of T cells that are involved in acute renal rejection. Hence, it is indicated for the treatment of acute allograft rejection in heart and liver transplant recipients resistant to standard steroid thcrapie.s. 

Shimizu, H., Takahashi, M., Kaneko, T., Murakami, T., Hakamata, Y., Kudou, S., Kishi, T., Fukuchi, K., Iwanami, S., Kuriyama, K., Yasue, T., Enosawa, S., Matsumoto, K., Takeyoshi, 1., Morishita, Y., Kobayashi, E. KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation 111 (2005) 222-229. 

Excessive apoptosis Neurodegenerative disorders (Alzheimers s disease, Parkinson s disease), hematological disorders, autoimmune disorders (graft versus host disease, type 1 diabetes, rheumatoid arthritis), ischemia, heart failure, inflammation, osteoarthritis, human immunodeficiency virus, bacterial infections, allograft rejection, trauma. 

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