Skip to main content
PMC home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1988 Nov;149(5):572–582.

Cardiac transplantation. Selection, immunosuppression, and survival.

L W Stevenson, H Laks, P I Terasaki, B D Kahan, D C Drinkwater
PMCID: PMC1026534  PMID: 3074557

Abstract

Cardiac transplantation has evolved from an experiment to an accepted therapy for severe heart failure. Increasing competition for donor organs mandates a greater emphasis on selection and timing for transplantation and paradoxically forces more reliance on aggressive medical therapy for all patients after evaluation. The growth of recipient and donor pools may enhance the opportunity for assessing histocompatibility, for which distinguishing between autoantibodies and human leukocyte antigen-determined reactivity is important, and some general nonresponders may be detected. Therapy with cyclosporine has improved the outcome after transplantation, but further refinement is needed, perhaps with pharmacologic synergy, to minimize nephrotoxicity and maximize specific immunosuppression. Survival is more than 80% at 1 year, after which the incidence of acute rejection and infection declines and accelerated atherosclerosis becomes prominent. Although resuming employment is not always possible, the overall quality of life is excellent after cardiac transplantation.

Full text

PDF
576

Images in this article

580Image
on p.580

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adu D., Lote C. J., Michael J., Turney J. H., McMaster P. Does cyclosporine inhibit renal prostaglandin synthesis? Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985;21:969–972. [PubMed] [Google Scholar]
  2. Bantle J. P., Nath K. A., Sutherland D. E., Najarian J. S., Ferris T. F. Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med. 1985 Mar;145(3):505–508. [PubMed] [Google Scholar]
  3. Barnard C. N. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J. 1967 Dec 30;41(48):1271–1274. [PubMed] [Google Scholar]
  4. Baxter C. R., Duggin G. G., Horvath J. S., Hall B. M., Tiller D. J. Cyclosporin A and renal prostaglandin biosynthesis. Res Commun Chem Pathol Pharmacol. 1984 Jul;45(1):69–80. [PubMed] [Google Scholar]
  5. Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
  6. Brown Z., Neild G. H. Cyclosporine inhibits prostacyclin production by cultured human endothelial cells. Transplant Proc. 1987 Feb;19(1 Pt 2):1178–1180. [PubMed] [Google Scholar]
  7. Calne R. Y., White D. J., Thiru S., Evans D. B., McMaster P., Dunn D. C., Craddock G. N., Pentlow B. D., Rolles K. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet. 1978 Dec 23;2(8104-5):1323–1327. doi: 10.1016/s0140-6736(78)91970-0. [DOI] [PubMed] [Google Scholar]
  8. Carrier M., Emery R. W., Riley J. E., Levinson M. M., Copeland J. G. Cardiac transplantation in patients over 50 years of age. J Am Coll Cardiol. 1986 Aug;8(2):285–288. doi: 10.1016/s0735-1097(86)80041-9. [DOI] [PubMed] [Google Scholar]
  9. Clark D. A., Stinson E. B., Griepp R. B., Schroeder J. S., Shumway N. E., Harrison D. C. Cardiac transplantation in man. VI. Prognosis of patients selected for cardiac transplantation. Ann Intern Med. 1971 Jul;75(1):15–21. doi: 10.7326/0003-4819-75-1-15. [DOI] [PubMed] [Google Scholar]
  10. Coffman T. M., Yarger W. E., Klotman P. E. Functional role of thromboxane production by acutely rejecting renal allografts in rats. J Clin Invest. 1985 Apr;75(4):1242–1248. doi: 10.1172/JCI111822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Colombani P. M., Robb A., Hess A. D. Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes. Science. 1985 Apr 19;228(4697):337–339. doi: 10.1126/science.3885394. [DOI] [PubMed] [Google Scholar]
  12. Curtis J. J., Luke R. G., Diethelm A. G., Whelchel J. D., Jones P. Benefits of removal of native kidneys in hypertension after renal transplantation. Lancet. 1985 Oct 5;2(8458):739–742. doi: 10.1016/s0140-6736(85)90627-0. [DOI] [PubMed] [Google Scholar]
  13. Cyclosporine. Heart and lung transplantation. Transplant Proc. 1983 Dec;15(4 Suppl 1-2):2546–2581. [PubMed] [Google Scholar]
  14. Davis R. J., Czech M. P. Amiloride directly inhibits growth factor receptor tyrosine kinase activity. J Biol Chem. 1985 Feb 25;260(4):2543–2551. [PubMed] [Google Scholar]
  15. De Vecchi A., Tarantino A., Montagnino G., Egidi F., Vegeto A., Berardinelli L., Ponticelli C. A controlled prospective trial of triple therapy with low-dose azathioprine, cyclosporine, and methylprednisolone in renal transplantation. Transplant Proc. 1987 Feb;19(1 Pt 3):1933–1934. [PubMed] [Google Scholar]
  16. Elzinga L., Kelley V. E., Houghton D. C., Bennett W. M. Modification of experimental nephrotoxicity with fish oil as the vehicle for cyclosporine. Transplantation. 1987 Feb;43(2):271–274. doi: 10.1097/00007890-198702000-00021. [DOI] [PubMed] [Google Scholar]
  17. Emery R. W., Cork R. C., Levinson M. M., Riley J. E., Copeland J., McAleer M. J., Copeland J. G. The cardiac donor: a six-year experience. Ann Thorac Surg. 1986 Apr;41(4):356–362. doi: 10.1016/s0003-4975(10)62686-0. [DOI] [PubMed] [Google Scholar]
  18. Ertel W., Reichenspurner H., Lersch C., Hammer C., Plahl M., Lehmann M., Kemkes B. M., Osterholzer G., Reble B., Reichart B. Cytoimmunological monitoring in acute rejection and viral, bacterial or fungal infection following transplantation. J Heart Transplant. 1985 Jul-Aug;4(4):390–394. [PubMed] [Google Scholar]
  19. Evans R. W., Manninen D. L., Garrison L. P., Jr, Maier A. M. Donor availability as the primary determinant of the future of heart transplantation. JAMA. 1986 Apr 11;255(14):1892–1898. [PubMed] [Google Scholar]
  20. Fidelus R. K., Laughter A. H. Protein kinase activation and the immunosuppressant cyclosporine. Transplantation. 1986 Feb;41(2):187–192. [PubMed] [Google Scholar]
  21. Fidelus R. K., Laughter A. H., Twomey J. J., Taffet S. M., Haddox M. K. The effect of cyclosporine on ornithine decarboxylase induction with mitogens, antigens, and lymphokines. Transplantation. 1984 Apr;37(4):383–387. doi: 10.1097/00007890-198404000-00014. [DOI] [PubMed] [Google Scholar]
  22. Foegh M. L., Khirabadi B., Ramwell P. W. Prolongation of experimental cardiac allograft survival with thromboxane-related drugs. Transplantation. 1985 Aug;40(2):124–125. doi: 10.1097/00007890-198508000-00002. [DOI] [PubMed] [Google Scholar]
  23. Granelli-Piperno A., Inaba K., Steinman R. M. Stimulation of lymphokine release from T lymphoblasts. Requirement for mRNA synthesis and inhibition by cyclosporin A. J Exp Med. 1984 Dec 1;160(6):1792–1802. doi: 10.1084/jem.160.6.1792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Griño J. M., Sabate I., Castelao A. M., Alsina J. Influence of diltiazem on cyclosporin clearance. Lancet. 1986 Jun 14;1(8494):1387–1387. doi: 10.1016/s0140-6736(86)91699-5. [DOI] [PubMed] [Google Scholar]
  25. Guthrie L. Arteritis obliterans of Right Upper Extremity associated with Malformation of both Clavicles. Proc R Soc Med. 1908;1(NEUROL):101–103. [PMC free article] [PubMed] [Google Scholar]
  26. Hall B. M., Sheil A. G., Tiller D. J., Hardie I., Mahoney J., Thatcher G., Mathew T., Thompson N., Miach P. Australian multicentre trial in cadaver renal transplantation comparison of short- and long-term cyclosporine A therapy with conventional therapy. Transplant Proc. 1987 Feb;19(1 Pt 3):1833–1834. [PubMed] [Google Scholar]
  27. Hiestand P. C., Mekler P., Nordmann R., Grieder A., Permmongkol C. Prolactin as a modulator of lymphocyte responsiveness provides a possible mechanism of action for cyclosporine. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2599–2603. doi: 10.1073/pnas.83.8.2599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Iaina A., Herzog D., Cohen D., Gavendo S., Kapuler S., Serban I., Schiby G., Eliahou H. E. Calcium entry-blockade with verapamil in cyclosporine A plus ischemia induced acute renal failure in rats. Clin Nephrol. 1986;25 (Suppl 1):S168–S170. [PubMed] [Google Scholar]
  29. Iwaki Y., Terasaki P. I., Heintz R., Cardman L., Hermes M. Enhancing antibody in human renal transplantation. Transplant Proc. 1979 Dec;11(4):1899–1902. [PubMed] [Google Scholar]
  30. Iwaki Y., Terasaki P. I. Sensitization effect. Clin Transpl. 1986:257–265. [PubMed] [Google Scholar]
  31. Kahan B. D., Lorber M. I., Flechner S. M., Van Buren C. T., Jensen C., Wideman C. A. Comparison of five cyclosporine-prednisone regimens for induction of immunosuppression in cadaveric kidney recipients: a retrospective analysis of 245 cases. Transplant Proc. 1986 Apr;18(2 Suppl 1):59–65. [PubMed] [Google Scholar]
  32. Kahan B. D., van Buren C. T., Flechner S. M., Jarowenko M., Yasumura T., Rogers A. J., Yoshimura N., LeGrue S., Drath D., Kerman R. H. Clinical and experimental studies with cyclosporine in renal transplantation. Surgery. 1985 Feb;97(2):125–140. [PubMed] [Google Scholar]
  33. Kawaguchi A., Goldman M. H., Shapiro R., Foegh M. L., Ramwell P. W., Lower R. R. Increase in urinary thromboxane B2 in rats caused by cyclosporine. Transplantation. 1985 Aug;40(2):214–216. doi: 10.1097/00007890-198508000-00022. [DOI] [PubMed] [Google Scholar]
  34. LOWER R. R., SHUMWAY N. E. Studies on orthotopic homotransplantation of the canine heart. Surg Forum. 1960;11:18–19. [PubMed] [Google Scholar]
  35. Lance E. M., Medawar P. Quantitative studies on tissue transplantation immunity. IX. Induction of tolerance with antilymphocytic serum. Proc R Soc Lond B Biol Sci. 1969 Jul 22;173(1033):447–473. doi: 10.1098/rspb.1969.0071. [DOI] [PubMed] [Google Scholar]
  36. LeGrue S. J., Friedman A. W., Kahan B. D. Binding of cyclosporine by human lymphocytes and phospholipid vesicles. J Immunol. 1983 Aug;131(2):712–718. [PubMed] [Google Scholar]
  37. Lelcuk S., Alexander F., Kobzik L., Valeri C. R., Shepro D., Hechtman H. B. Prostacyclin and thromboxane A2 moderate postischemic renal failure. Surgery. 1985 Aug;98(2):207–212. [PubMed] [Google Scholar]
  38. MURRAY J. E., MERRILL J. P., DAMMIN G. J., DEALY J. B., Jr, ALEXANDRE G. W., HARRISON J. H. Kidney transplantation in modified recipients. Ann Surg. 1962 Sep;156:337–355. doi: 10.1097/00000658-196209000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McMillen M. A., Baumgarten W. K., Schaefer H. C., Mitchnick E., Fuortes M., Holman M. J., Tesi R. J. The effect of verapamil on cellular uptake, organ distribution, and pharmacology of cyclosporine. Transplantation. 1987 Sep;44(3):395–401. doi: 10.1097/00007890-198709000-00014. [DOI] [PubMed] [Google Scholar]
  40. Moss N. G., Powell S. L., Falk R. J. Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8222–8226. doi: 10.1073/pnas.82.23.8222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Murray B. M., Paller M. S., Ferris T. F. Effect of cyclosporine administration on renal hemodynamics in conscious rats. Kidney Int. 1985 Nov;28(5):767–774. doi: 10.1038/ki.1985.196. [DOI] [PubMed] [Google Scholar]
  42. Myers B. D., Ross J., Newton L., Luetscher J., Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med. 1984 Sep 13;311(11):699–705. doi: 10.1056/NEJM198409133111103. [DOI] [PubMed] [Google Scholar]
  43. Nephrotoxicity of cyclosporine. N Engl J Med. 1985 Jan 3;312(1):48–50. doi: 10.1056/NEJM198501033120112. [DOI] [PubMed] [Google Scholar]
  44. Neumayer H. H., Wagner K. Diltiazem and economic use of cyclosporin. Lancet. 1986 Aug 30;2(8505):523–523. doi: 10.1016/s0140-6736(86)90398-3. [DOI] [PubMed] [Google Scholar]
  45. Nussenblatt R. B., Austin H. A., 3rd, Palestine A. G., Preuss H. G. Hydergine and cyclosporin nephrotoxicity. Lancet. 1986 May 24;1(8491):1220–1221. doi: 10.1016/s0140-6736(86)91209-2. [DOI] [PubMed] [Google Scholar]
  46. Ozturk G., Terasaki P. I. Non-HLA lymphocyte cytotoxins in various diseases. Tissue Antigens. 1979 Jul;14(1):52–58. doi: 10.1111/j.1399-0039.1979.tb00821.x. [DOI] [PubMed] [Google Scholar]
  47. Paller M. S., Murray B. M. Renal dysfunction in animal models of cyclosporine toxicity. Transplant Proc. 1985 Aug;17(4 Suppl 1):155–159. [PubMed] [Google Scholar]
  48. Park M. S., Terasaki P. I., Bernoco D. Autoantibody against B lymphocytes. Lancet. 1977 Sep 3;2(8036):465–467. doi: 10.1016/s0140-6736(77)91598-7. [DOI] [PubMed] [Google Scholar]
  49. Paulsen W., Magid N., Sagar K., Hastillo A., Wolfgang T. C., Lower R. R., Hess M. L. Left ventricular function of heart allografts during acute rejection: an echocardiographic assessment. J Heart Transplant. 1985 Sep-Oct;4(5):525–529. [PubMed] [Google Scholar]
  50. Penn I. Cancer is a complication of severe immunosuppression. Surg Gynecol Obstet. 1986 Jun;162(6):603–610. [PubMed] [Google Scholar]
  51. Perico N., Benigni A., Zoja C., Delaini F., Remuzzi G. Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A. Am J Physiol. 1986 Oct;251(4 Pt 2):F581–F587. doi: 10.1152/ajprenal.1986.251.4.F581. [DOI] [PubMed] [Google Scholar]
  52. Reem G. H., Cook L. A., Vilcek J. Gamma interferon synthesis by human thymocytes and T lymphocytes inhibited by cyclosporin A. Science. 1983 Jul 1;221(4605):63–65. doi: 10.1126/science.6407112. [DOI] [PubMed] [Google Scholar]
  53. Russell D. H., Kibler R., Matrisian L., Larson D. F., Poulos B., Magun B. E. Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine. J Immunol. 1985 May;134(5):3027–3031. [PubMed] [Google Scholar]
  54. Ryffel B., Siegl H., Petric R., Muller A. M., Hauser R., Mihatsch M. J. Nephrotoxicity of cyclosporine in spontaneously hypertensive rats: effects on blood pressure and vascular lesions. Clin Nephrol. 1986;25 (Suppl 1):S193–S198. [PubMed] [Google Scholar]
  55. Salaman J. R., Griffin P. J. Immunosuppression with a combination of cyclosporin, azathioprine, and prednisolone may be unsafe. Lancet. 1985 Nov 9;2(8463):1066–1067. doi: 10.1016/s0140-6736(85)90932-8. [DOI] [PubMed] [Google Scholar]
  56. Schüler S., Warnecke H., Hetzer R. Prevention of toxic side effects of cyclosporine in heart transplantation. Transplant Proc. 1987 Feb;19(1 Pt 3):2518–2521. [PubMed] [Google Scholar]
  57. Simmons R. L., Canafax D. M., Strand M., Ascher N. L., Payne W. D., Sutherland D. E., Najarian J. S. Management and prevention of cyclosporine nephrotoxicity after renal transplantation: use of low doses of cyclosporine, azathioprine, and prednisone. Transplant Proc. 1985 Aug;17(4 Suppl 1):266–275. [PubMed] [Google Scholar]
  58. Solis E., Kaye M. P. The Registry of the International Society for Heart Transplantation: third official report--June 1986. J Heart Transplant. 1986 Jan-Feb;5(1):2–5. [PubMed] [Google Scholar]
  59. Stahl R. A., Kudelka S. Chronic cyclosporine A treatment reduces prostaglandin E2 formation in isolated glomeruli and papilla of rat kidneys. Clin Nephrol. 1986;25 (Suppl 1):S78–S82. [PubMed] [Google Scholar]
  60. Stevenson L. W., Bellil D., Grover-McKay M., Brunken R. C., Schwaiger M., Tillisch J. H., Schelbert H. R. Effects of afterload reduction (diuretics and vasodilators) on left ventricular volume and mitral regurgitation in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1987 Sep 15;60(8):654–658. doi: 10.1016/0002-9149(87)90376-6. [DOI] [PubMed] [Google Scholar]
  61. Stevenson L. W., Donohue B. C., Tillisch J. H., Schulman B., Dracup K. A., Laks H. Urgent priority transplantation: when should it be done? J Heart Transplant. 1987 Sep-Oct;6(5):267–272. [PubMed] [Google Scholar]
  62. Stevenson L. W., Fowler M. B., Schroeder J. S., Stevenson W. G., Dracup K. A., Fond V. Poor survival of patients with idiopathic cardiomyopathy considered too well for transplantation. Am J Med. 1987 Nov;83(5):871–876. doi: 10.1016/0002-9343(87)90644-9. [DOI] [PubMed] [Google Scholar]
  63. Stevenson L. W., Lewis W., MacAlpin R. N., Clark S. Acute reversible cardiogenic shock: immune-mediated with mild histologic change. Am Heart J. 1986 Mar;111(3):611–613. doi: 10.1016/0002-8703(86)90079-7. [DOI] [PubMed] [Google Scholar]
  64. Stevenson L. W., Tillisch J. H. Maintenance of cardiac output with normal filling pressures in patients with dilated heart failure. Circulation. 1986 Dec;74(6):1303–1308. doi: 10.1161/01.cir.74.6.1303. [DOI] [PubMed] [Google Scholar]
  65. Stiller C. R., Keown P. A., Heinrichs D., Martell R., Dupre J., Jenner M., Rodger W., Wolfe B. The effect of cyclosporine of renal function in newly diagnosed diabetics. Transplant Proc. 1985 Aug;17(4 Suppl 1):202–208. [PubMed] [Google Scholar]
  66. Stork J. E., Rahman M. A., Dunn M. J. Eicosanoids in experimental and human renal disease. Am J Med. 1986 Jan 17;80(1A):34–45. doi: 10.1016/0002-9343(86)90930-7. [DOI] [PubMed] [Google Scholar]
  67. Szentpetery S., Thames M., Hanrahan J., Morris J., Lower R. R. Cardiac transplantation in the sixth decade of life. Transplant Proc. 1987 Feb;19(1 Pt 3):2492–2494. [PubMed] [Google Scholar]
  68. Szentpetery S., Thames M., Hanrahan J., Morris J., Lower R. R. Cardiac transplantation in the sixth decade of life. Transplant Proc. 1987 Feb;19(1 Pt 3):2492–2494. [PubMed] [Google Scholar]
  69. Vincent H. H., Wenting G. J., Jeekel J., Schalekamp M. A., Weimar W. Dihydroergotoxine (hydergine) to prevent cyclosporine nephrotoxicity in kidney transplant recipients. Transplant Proc. 1987 Feb;19(1 Pt 2):1737–1738. [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES