Pharmacological intervention to decrease ischemia-reperfusion injury

  • J. M. Grinyó
Part of the Transplantation and Clinical Immunology book series (TRAC, volume 30)


The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid-organ transplantation. Cell alterations induced by ischemia prime the tissue for the subsequent damage that occurs during the reperfusion phase. Paradoxically, re-establishing blood flow to ischemic tissues may cause greater injury than that induced during the ischemic period. Ischemia-reperfusion injury is a complex sequence of events that mainly involves the vascular endothelium in the microcirculation and neutrophils. Interruption of blood supply and lack of oxygen during ischemia lead to anaerobic metabolism that entails a depletion of adenosine 5 -triphosphate (ATP) [1–3]. Depletion of these nucleotides alters the membrane ionic ATP-dependent pumps which favors the entry of calcium, sodium and water into the cell [4–6]. The catabolism of adenine nucleotides results in an accumulation of hypoxanthine within ischemic cells [7]. Also, ischemia is associated with the proteolytic conversion of xanthine/hypoxanthine dehydrogenase to xanthine/hypoxanthine oxidase [8].


Nitric Oxide Reperfusion Injury Reactive Oxygen Metabolite Proteolytic Conversion Soluble Complement Receptor Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Kamiike W, Burdelski M, Steinhoff G, Ringe B, Lauchart W, Pichlmayer R. Transplantation. 1988; 45: 138–143.PubMedCrossRefGoogle Scholar
  2. 2.
    Geen CJ, Gower JD, Healing G, Cotterill LA, Fuller BJ, Simpkin S. Free Radic. Res. Commun. 1989; 7: 255–264.CrossRefGoogle Scholar
  3. 3.
    Vigués F, Ambrosio S, Bartrons R et al. Transplant. Int. 1994; 7: 96–100.CrossRefGoogle Scholar
  4. 4.
    Fitzpatrick DB, Karmazyn M. J. Pharmacol. Exp. Ther. 1984; 228: 737–757.Google Scholar
  5. 5.
    Wilson DR, Arnold PE, Burke TJ, Scrier RW. Kidney Int. 1984; 25: 519–526.PubMedCrossRefGoogle Scholar
  6. 6.
    Cross HR, Radda GK, Clarke K. Magn. Reson. Med. 1995; 34: 673–685.PubMedCrossRefGoogle Scholar
  7. 7.
    Mandel LJ, Takano T, Soltoff SP, Murdaugh S. J. Clin. Invest. 1988; 81: 1255–1264.CrossRefGoogle Scholar
  8. 8.
    Engerson TD, McKelvey DB, Boggio EB, Snyder SJ, Jones HP. J. Clin. Invest. 1987; 79: 1564–1570.CrossRefGoogle Scholar
  9. 9.
    Freeman BA, Crapo JD. Lab. Invest. 1982; 47: 412–426.PubMedGoogle Scholar
  10. 10.
    Mead JF. Free Radicals in Biology. New York: Academic Press; 1976: vol. 1, pp. 51–68.Google Scholar
  11. 11.
    Whorton AR, Willis CE, Kent RS, Young SL. Lipids. 1984; 19: 17–24.PubMedCrossRefGoogle Scholar
  12. 12.
    Whatley RE, Zimmerman GA, McIntyre TM, Prescott SM. Prog. Lipid. Res. 1990; 29: 45–63.PubMedCrossRefGoogle Scholar
  13. 13.
    Whatley RE, Zimmerman GA, Stevens DL et al. J. Biol. Chem. 1989; 264: 6325–6333.PubMedGoogle Scholar
  14. 14.
    Zimmerman GA, Prescott SM, McIntyre TM. Immunol. Today. 1992; 13: 93–100.PubMedCrossRefGoogle Scholar
  15. 15.
    Imaizumi T, Stafforini DM, Yamada Y, McIntyre TM, Prescott SM, Zimmerman GA. J. Int. Med. 1995; 238: 5–20.CrossRefGoogle Scholar
  16. 16.
    Patel KD, Zimmerman GA, Prescott SM et al. J. Cell. Biol. 1992; 267: 15618–15175.Google Scholar
  17. 17.
    Patel KD, Zimmerman GA, Prescott SM et al. J. Cell. Biol. 1991; 112: 749–759.PubMedCrossRefGoogle Scholar
  18. 18.
    Lorant De, Patel KD, McIntyre TM et al. J. Cell. Biol. 1991; 115: 223–234.PubMedCrossRefGoogle Scholar
  19. 19.
    Inauen W, Granger DN, Meininger DJ, Schelling ME, Ganger Hi, Kviets PR. Am. J. Physiol. 1990; 259: H925–H931.PubMedGoogle Scholar
  20. 20.
    Weiss SJ. N. Engl. J. Med. 1989; 320: 365–376.PubMedCrossRefGoogle Scholar
  21. 21.
    DeForge LE, Fantone JC, Kenney JS, Remick DG. J. Clin. Invest. 1992; 90: 2123–2129.PubMedCrossRefGoogle Scholar
  22. 22.
    Neumann FJ, Ott I, Gawaz M et al. Circulation. 1995; 92: 748–755.PubMedCrossRefGoogle Scholar
  23. 23.
    Huber Ar, Kunkel SL, Todd RF III, Weiss SJ. Science. 1991; 250: 99–102.CrossRefGoogle Scholar
  24. 24.
    Takahashi M, Masuyama J, Ikeda U et al. Cardiovasc. Res. 1995; 29: 670–675.PubMedGoogle Scholar
  25. 25.
    Windsor AJC, Mullen PG, Fowler AA, Sugerman HJ. Br. J. Surg. 1993; 80: 10–17.PubMedCrossRefGoogle Scholar
  26. 26.
    Muller WA, Weigl SA, Deng X, Philips DM. J. Exp. Med. 1993; 178: 449–460.PubMedCrossRefGoogle Scholar
  27. 27.
    Hugo F, Hamdoch T, Mathey D, Shafer H, Bhakdi S. Clin. Exp. Immunol. 1990; 81: 132–136.PubMedCrossRefGoogle Scholar
  28. 28.
    Shafer PJ, Mathey D, Hugo F, Bhakdi S. J. Immunol. 1986; 137: 1945–1949.Google Scholar
  29. 29.
    Weiser MR, Williams JP, Moore FD et al. Clin. Exp. Immunol. 1996; 183: 2343–2348.Google Scholar
  30. 30.
    Firth JD, Ratcliffe PJ. J. Clin. Invest. 1992; 90: 1023–1031.PubMedCrossRefGoogle Scholar
  31. 31.
    Sternberg WC, Makhoul RG, Adelman B. Surgery. 1992; 114: 960–967.Google Scholar
  32. 32.
    Ma X-L, Weyrich AS, Lefer DJ, Lefer AM. Circ. Res. 1993; 72: 403–412.PubMedCrossRefGoogle Scholar
  33. 33.
    Yu L, Gengaro M, Niedberger M, Burke T, Schrier RW. Proc. Natl. Acad. Sci. USA. 1994; 91: 1691–1695.PubMedCrossRefGoogle Scholar
  34. 34.
    Noiri E, Peresleni E, Miller F, Goligorski MS. J. Clin. Invest. 1996; 97: 2377–2383.PubMedCrossRefGoogle Scholar
  35. 35.
    Torras J, Seron D, Herrero I et al. Transplant. Int. 1994; 7(Suppl. 1): S472–S475.CrossRefGoogle Scholar
  36. 36.
    Land W, Schneeberger H, Schleibner S et al. Transplantation. 1994; 57: 211–217.PubMedCrossRefGoogle Scholar
  37. 37.
    Green CJ, Healing G, Simpkin S, Lunee J, Fuller BJ. Comp. Biochem. Physiol. (B). 1986: 85: 113–117.Google Scholar
  38. 38.
    Nishida T, Morita S, Miyamoto K et al. Transplantation. 1996; 61: 194–199.PubMedCrossRefGoogle Scholar
  39. 39.
    Leleuk S, Alexander F, Kobcick L, Valeri CR, Shepro D, Hechman HB. Surgery. 1985; 98: 202–212.Google Scholar
  40. 40.
    Kuzu Ma, Köksoy C, Alaçayir I, Yazar O, Kuterdem E. Transplantation. 1995; 59: 1096–1099.PubMedGoogle Scholar
  41. 41.
    Klausner JM, Paterson IS, Kobcick L et al. Ann. Surg. 1989; 209: 219–224.PubMedCrossRefGoogle Scholar
  42. 42.
    Neumayer HH, Wagner K, Preuschof L, Stanke H, Shultze G, Molzahn M. J. Cardiovasc. Pharmacol. 1986; 8: 785–790.PubMedGoogle Scholar
  43. 43.
    Torras J, Soto K, Riera M et al. Transplant. Int. 1996; 9(Suppl. 1): S455–S459.CrossRefGoogle Scholar
  44. 44.
    Svendsen JH, Hansen PR, Ah S, Baandrup U, Haunse S. Cardiovasc. Res. 1993; 27: 1288–1294.PubMedCrossRefGoogle Scholar
  45. 45.
    Steimle CN, Guynn TP, Morganroth ML, Bolling SF, Carr K, Deeb JM. Ann. Thorac. Surg. 1992; 53: 64–73.PubMedCrossRefGoogle Scholar
  46. 46.
    Sawa Y, Schaper J, Roth M et al. J. Thorac. Cardiovasc. Surg. 1994; 108: 953–959.PubMedGoogle Scholar
  47. 47.
    Torras J, Bordalba JR, Seron D et al. Transplant. Int. 1993; 6: 236–238.CrossRefGoogle Scholar
  48. 48.
    Riera M, Torras J, Herrero I et al. J. Pharmacol. Exp. Ther. (In press).Google Scholar
  49. 49.
    Raschke P, Becker BF. Cardiovasc. Res. 1995; 29: 569–576.PubMedGoogle Scholar
  50. 50.
    Takada Y, Boudjema K, Jaeck D et al. Transplantation. 1995; 59: 10–16.PubMedCrossRefGoogle Scholar
  51. 51.
    Grino JM. Ann. Intern. Med. 1994; 121: 345–347.PubMedGoogle Scholar
  52. 52.
    Tjoelker LW, Wilder C, Eberhardt C et al. Nature. 1995; 374: 549–552.PubMedCrossRefGoogle Scholar
  53. 53.
    Darbinian SH, Roberts RF, Carey JN et al. 16th Annual Meeting of the American Society of Transplant Physicians. Chicago, May 1997. Abstract Book p. 245.Google Scholar
  54. 54.
    Hansen PR. Circulation. 1995; 91: 1872–1885.PubMedCrossRefGoogle Scholar
  55. 55.
    Haller H, Dragun D, Miethke A et al. Kidney Int. 1996; 50: 473–480.PubMedCrossRefGoogle Scholar
  56. 56.
    Sekido N, Mukaida N, Harada A, Nakanishi I, Watanabe I, Matsushima K. Nature. 1993; 365: 654–657.PubMedCrossRefGoogle Scholar
  57. 57.
    Weiman HF, Bartow T, Leppo MK et al. Science. 1990; 249: 146–151.CrossRefGoogle Scholar
  58. 58.
    Chavez-Cartaya RE, DeSola GP, Wright L, Jamieson NV, White DJ. Transplantation. 1995; 59: 1047–1052.PubMedCrossRefGoogle Scholar
  59. 59.
    Nicolini FA, Metha JL, Nichols WW, Donnelly WH, Luostarinen R, Saldeen TGP. Am. Heart J. 1991; 122: 1245–1251.PubMedCrossRefGoogle Scholar
  60. 60.
    Hirano T, Furuyama H, Kawakami Y, Ando K, Tsuchitani T. Can. J. Surg. 1995; 38: 241–248.PubMedGoogle Scholar
  61. 61.
    Murohara T, Guo JP, Lefer AM. J. Pharmacol. Exp. Ther. 1995; 274: 1246–1253.PubMedGoogle Scholar
  62. 62.
    Siegfred MR, Erhardt J, Rider T, Ma X-L, Lefer AM. J. Pharmacol. Exp. Ther. 1992; 260: 668–675.Google Scholar
  63. 63.
    Siegfried MR, Carey C, Max-L, Lefer AM. Am. J. Physiol. 1992; 263: H771–H777.PubMedGoogle Scholar
  64. 64.
    Gellai M, Jugus M, Fletcher T, DeWolf R, Nambi P. J. Clin. Invest. 1994; 93: 900–906.PubMedCrossRefGoogle Scholar
  65. 65.
    Krause SM, Walsh TF, Greenlee WJ, Ranaei R, Williams DL, Kivlighn SD. J. Am. Soc. Nephrol. 1997; 8: 1061–1071.PubMedGoogle Scholar
  66. 66.
    Herrero I, Torras J, Riera M et al. J. Am. Soc. Nephrol. 1997; 8: 657A (abstract).Google Scholar
  67. 67.
    Osborne DL, Aw TY, Cepinskas G, Kvietys PR. J. Clin. Invest. 1994; 94: 1910–1918.PubMedCrossRefGoogle Scholar
  68. 68.
    Saitoh Y, Gu K, Kin S et al. Transplantation. 1995; 60: 1079–1083.PubMedCrossRefGoogle Scholar
  69. 69.
    Yamashita N, Nishida M, Hoshida S et al. J. Clin. Invest. 1994; 94: 2193–2199.PubMedCrossRefGoogle Scholar
  70. 70.
    Gho BCG, Eskildsen-Heldmon YEG, de Zeeuw S, Lamers JMJ, Verdouw PD. Cardiovasc. Drugs Ther. 1996; 10: 775–786.CrossRefGoogle Scholar
  71. 71.
    Chiao H, Kohda Y, McLeroy P, Craig L, Housini Y, Star RA. J. Clin. Invest. 1997; 99: 1165–1172.PubMedCrossRefGoogle Scholar
  72. 72.
    Paul LC, Zhang S. Valentin J-F, Brujin JA. 16th Annual Meeting of the American Society of Transplant Physicians. Chicago, May 1997. Abstract Book p. 190.Google Scholar

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© Springer Science+Business Media Dordrecht 1998

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  • J. M. Grinyó

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