The effect of cyclosporin�A on the level of big endothelin in patients one year after orthotopic heart transplantation

Abstract

Orthotopic heart transplantation (OHTx) is currently an established method for the treatment of end-stage heart failure. Persistent elevated plasma endothelin-1 (ET-1) levels have been reported after successful OHTx, the etiology of which is not yet fully understood. Immunosuppressive therapy is assumed to be one of the possible factors affecting ET-1 levels in the body. The present study evaluated the effect of cyclosporin A (CyA) on big ET-1 levels (a precursor of ET-1) in patients 1 year after successful OHTx. The study population comprised 34 patients after OHTx (28 males, 6 females, mean age 49.56+/-11.83 years) divided into two groups according to immunosuppressive protocol (17 patients on cyclosporine-azathioprine-prednisone and 17 patients on cyclosporine-mycophenolate mofetil-prednisone therapy). Plasma levels of big ET-1 and CyA were available for all patients. The control groups consisted of 10 healthy individuals (8 males, 2 females, mean age 41.1+/-11.55 years) and 20 patients with severe heart failure (15 males, 5 females, mean age 54.45+/-8.49 years), respectively. Big ET-1 plasma levels were found to be elevated in OHTx patients in comparison with healthy controls (13.63+/-11.3 fmol/ml vs 2.99+/-1.98 fmol/ml, P=0.005). Big ET-1 plasma levels correlated with plasma CyA levels in patients treated with cyclosporine-azathioprine-prednisone ( r=0.53, P=0.03). This was not the case in either in the OHTx patients as a whole or in the subgroup of patients on cyclosporine-mycophenolate mofetil-prednisone therapy. The plasma levels of big ET-1 are dependent on CyA plasma levels 1 year after successful OHTx in patients treated with the immunosuppressive combination of cyclosporine, azathioprine, and prednisone. As this finding was not observed in the mycophenolate group of patients, mycophenolate mofetil might affect the alteration of the endothelin metabolism.

Follicle growth and oocyte development after ovary transplantation into back muscle of immune-intact adult castrated male mice

“…It was found that cyclosporine A plus steroids was also needed for ovarian allografts to survive (Cornier et al 1985, Scott et al 1987. Based on previous reports (Kocik et al 2004), three suppressants were used in our study, we found that they worked well without serious side effects or infection; the main physiological indexes were normal, including diet, temperature, spleen size, and blood vessel re-establishment around the grafts after transfer. Although there was also an inflammatory infiltration around some grafts with immunosuppressant treatment, our study strongly showed that both the recovery rate (23.5%) and structure of the grafts without immunosuppressants were much worse than the control (recovery rate, 67%), and that the immunosuppressive therapy was effective in ovarian transplantation in mice.…”

“…Based on the study of Kocik et al (2004), a combination of cyclosporine, azathioprine, and prednisone was used as immunosuppressants in this study. Before immunosuppressant treatment, the cyclosporine (BBI Co., Kitchener, Ontario, Canada) was first dissolved in absolute ethanol, and then redissolved in olive oil to a final concentration of 15 mg/ml (4% ethanol; Zhang et al 2003).…”

Recent Developments on Endothelin Antagonists as Immunomodulatory Drugs - from Infection to Transplantation Medicine

“…Enhanced levels of ET-1 lead to constriction of smooth muscle cells and cell proliferation, as could be shown in cell culture experiments [193,194]. The plasma levels of big ET-1 are dependent on CNI plasma levels 1 year after successful heart transplantation in patients [195]. Previous studies using ET A receptor antagonism have used concomitant immunosuppressive therapy [15]; thus, the potential immunomodulatory actions of ET-1 and the actual contribution of ET-1 to chronic rejection were masked because of the immunosuppressive agents.…”