AN ASSESSMENT OF NVA2-CYCLOSPOMNE IN PRIMATE CARDIAC TRANSPLANTATION
| Autor: | Margaret E. Billingham, Stuart W. Jamieson, Starkey Td, John C. Baldwin, Kendrick A. Porter, Harry O. Ogunnaike |
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| Rok vydání: | 1987 |
| Předmět: |
medicine.medical_specialty
Time Factors Bilirubin medicine.medical_treatment Urology Cyclosporins Nephrotoxicity chemistry.chemical_compound medicine Animals Blood urea nitrogen Immunosuppression Therapy Heart transplantation Transplantation Creatinine Maintenance dose business.industry Myocardium Immunosuppression Surgery Macaca fascicularis chemistry Cyclosporine Heart Transplantation Kidney Diseases Chemical and Drug Induced Liver Injury business |
| Zdroj: | Transplantation. 43:13-17 |
| ISSN: | 0041-1337 |
| Popis: | The immunosuppressive potency, hepatotoxicity, and nephrotoxicity of Norvaline2-cyclosporine (Nva2-CsA), an analog of cyclosporine (CsA), were tested in a primate cardiac transplant model. After orthotopic cardiac transplantation in cynomolgus monkeys, immunosuppression was maintained with 16 mg/kg/day of either CsA or Nva2-CsA given intramuscularly in two divided daily doses. Immunosuppression was augmented with i.m. methyl-prednisolone, 1.0 mg/kg/day, which was tapered weekly by .1 mg/kg/day to a maintenance dose of .1 mg/kg/day. A group of 6 untransplanted monkeys were treated for a year with this dose of either CsA or Nva2-CsA and steroids. Renal biopsies were performed at one year. Among the transplanted monkeys, mean survival was 77.3 +/- 73 days for the CsA group and 16 +/- 8 days for the Nva2-CsA group. All 11 animals in the Nva2-CsA group died of cardiac rejection, but only 7 of 10 treated with CsA died of rejection. There was mild hepatic and renal dysfunction in both treatment groups, but no significant difference between groups as judged by blood urea nitrogen, creatinine, total bilirubin, serum glutamic oxaloacetic transaminate, and alkaline phosphatase. Cyclosporine levels were significantly higher in the CsA group. There were important morphological changes in both groups on histological examination of the kidneys, with proximal tubular vacuolation and enlargement of the juxtaglomerular apparatus predominating. It is concluded that Nva2-CsA is a less effective immunosuppressant than CsA when given parenterally in equal doses. |
| Databáze: | OpenAIRE |
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