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Ann Thorac Surg 1988;45:158-163
© 1988 The Society of Thoracic Surgeons


Articles

Value of Urinary Polyamines as Noninvasive Markers of Cardiac Allograft Rejection in the Dog

Michel Carrier, M.D.*, Diane H. Russell, Ph.D., Thomas P. Davis, Ph.D., Robert W. Emery, M.D., Jack G. Copeland, M.D.

From the Departments of Cardiovascular and Thoracic Surgery and of Pharmacology, University of Arizona, Tucson, AZ

* Address reprint requests to Dr. Carrier, Montreal Heart Institute, 5000 E Belanger St, Montreal, Que, Canada H1T 1C8


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A noninvasive marker of cardiac allograft rejection would be useful clinically. Lymphocyte proliferation and organ rejection may cause changes in urinary polyamine excretion. To test this hypothesis, cervical heterotopic heart transplantations were performed in a group of 6 nonimmunosuppressed dogs and in a group of 9 dogs treated with cyclosporine (N = 3) or cyclosporine and steroids (N = 6). A group (N = 3) having a sham operation was also studied. Serial biopsies of the transplanted hearts were performed. Urinary polyamine levels were measured daily by high-pressure liquid chromatography of urine specimens. Between 2 and 4 days after transplantation, the transplanted hearts of all animals without immunosuppression demonstrated histological rejection. An early increase in putrescine levels and in total urinary polyamine levels was observed in this group. In the treated groups, histological rejection appeared from the second to the eighth day after transplantation. Each episode of rejection occurred from 1 day to 4 days after a significant increase in urinary polyamine levels compared with the preoperative baseline level (p < 0.01). In contrast, polyamine excretion in 3 dogs after sham operations remained unchanged. Thus, urinary excretion of polyamines increases before the appearance of histological rejection; this suggests that changes in urinary polyamine levels may be a useful marker of cardiac allograft rejection.


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Presented at the Twenty-third Annual Meeting of The Society of Thoracic Surgeons, Toronto, Ont, Canada, Sept 21–23, 1987.


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  1. Billingham ME. Diagnosis of cardiac rejection by endomyocardial biopsy J Heart Transplant 1981;1:25.
  2. Copeland JG, Emery RW, Levinson MM, et al. Cyclosporine: an immunosuppressive panacea? J Thorac Cardiovasc Surg 1986;91:26.[Abstract]
  3. Caves PK, Stinson EB, Billingham ME, et al. Diagnosis of human cardiac allograft rejection by serial cardiac biopsy J Thorac Cardiovasc Surg 1973;66:461.[Medline]
  4. Novitzky D, Rose AG, Cooper DKC, Reichart B. Histopathologic changes at the site of endomyocardial biopsy: potential for confusion with acute rejection J Heart Transplant 1986;5:79.
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  7. Womble JR, Larson DF, Copeland JG, Russell DH. Urinary polyamine levels are markers of altered T lymphocyte proliferation/loss and rejection in heart transplant patients Transplant Proc 1984;16:1573.[Medline]
  8. Russell DH, Durie BGM. Polyamines as biochemical markers of normal and malignant growthIn: Russell DH, Durie BGM, editors. Progress in Cancer Research Therapy. Vol. 8. New York: Raven; 1978. pp. 1-13.
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  11. Menashe M, Faber J, Bachrach U. Formation of N-acetylputrescine and N1-acetylspermidine in cultured human lymphocytes Biochem J 1980;188:263.[Medline]
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  17. Ertel W, Reichenspurner H, Lersch C, et al. Cytoimmunologic monitoring in acute rejection and viral, bacterial or fungal infection following transplantation J Heart Transplant 1985;4:390.[Medline]
  18. Painvin GA, Heimbecker RO, Keown PA, et al. The side effects of cyclosporin A: clinical and histologic finding following 31 canine heterotopic cardiac allotransplantations Curr Surg 1983;Mar/Apr:120.




This Article
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Right arrow Articles by Copeland, J. G.