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Role of Ischemia/Reperfusion Injury in Organ Transplantation

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The Role of Immune Mechanisms in Cardiovascular Disease
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Abstract

Reperfusion of oxygenated blood into previously ischemic tissue is essential to prevent the progression of cellular injury due to the decreased nutritional blood flow, i.e., the decreased delivery of oxygen and metabolic substrates, as well as the removal of harmful metabolic byproducts. However, it has become obvious that reperfusion also initiates a complex series of pathologic events that contribute to, rather than prevent, further tissue damage. Moreover, a growing body of evidence indicates that ischemia/reperfusion injury is initiated by events that occur at the level of the microcirculation. In the first part of this overview, we will delineate the major components of the microcirculatory manifestations of ischemia reperfusion injury. In the second part, we will focus on a distinct pathophysiological condition in which these microcirculatory manifestations of ischemia/reperfusion injury are operative: the loss of long-term allograft function after organ transplantation.

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References

  1. Cala PM, Anderson SE, Cragoe EJ (1988) Na/H exchange-dependent cell volume and pH regulation and disturbances. Comp Biochem Physiol Physiol 90A: 551–555

    Article  CAS  Google Scholar 

  2. Nakayama S, Kramer GC, Carlsen RC, Holcroft JW (1985) Infusion of very hypertonic saline to bled rats: membrane potentials and fluid shifts. J Surg Res 38: 180–186

    Article  PubMed  CAS  Google Scholar 

  3. Flores J, DiBona DR, Beck CH, Leaf A (1972) The role of cell swelling in ischemic renal damage and the protective effect of hypertonic solute. J Clin Invest 51: 118–126

    Article  PubMed  CAS  Google Scholar 

  4. Gidlöf A, Lewis DH, Hammersen F (1987) The effect of prolonged total ischemia on the ultrastructure of human skeletal muscle capillaries. A morphometric analysis. Int J Mi-crocirc Clin Exp 7: 67–86

    Google Scholar 

  5. Mazzoni MC, Borgstrom P, Intaglietta M, Arfors KE (1989) Lumenal narrowing and endothelial cell swelling in skeletal muscle capillaries during hemorrhagic shock. Circ Shock 29: 27–29

    PubMed  CAS  Google Scholar 

  6. Nolte D, Bayer M, Lehr HA, Becker M, Krombach F, Kreimeier U, Messmer K (1992) Attenuation of post-ischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran. Am J Physiol 263: H1411–H1416

    PubMed  CAS  Google Scholar 

  7. Menger MD, Steiner D, Messmer K (1992) Microvascular ischemia-reperfusion injury in striated muscle: significance of “no-reflow”. Am J Physiol 263: H1892–H1900

    PubMed  CAS  Google Scholar 

  8. Messmer K, Sack FU, Menger MD, Bartlett R, Barker JH, Hammersen F (1988) White cell-endothelium interaction during postischemic reperfusion of skin skeletal muscle. Adv Exp Med Biol 242: 95–98

    PubMed  CAS  Google Scholar 

  9. Lehr HA, Hübner C, Nolte D, Kohlschütter A, Messmer K (1991) Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters. Proc Natl Acad Sci USA 88: 6726–6730

    Article  PubMed  CAS  Google Scholar 

  10. Menger MD, Pelikan S, Steiner D, Messmer K (1992) Microvascular ischemia-reperfusion injury in striated muscle: significance of “reflow paradox”. Am J Physiol 263: H1901–H1906

    PubMed  CAS  Google Scholar 

  11. Becker M, Menger MD, Lehr HA (1994) Heparin-released superoxide dismutase inhibits post-ischemic leukocyte adhesion to venular endothelium. Am J Physiol 267: H925–H930

    PubMed  CAS  Google Scholar 

  12. Willy C, Thiery J, Menger MD, Messmer K, Arfors KE, Lehr HA (1995) Impact of vitamin E supplement in standard laboratory animal diet on microvascular manifestation of ische-mia/reperfusion injury. Free Radic Biol Med 19: 919–926

    Article  PubMed  CAS  Google Scholar 

  13. Nolte D, Menger MD, Messmer K (1995) Microcirculatory models of ischaemia-reperfu-sion in skin and striated muscle. Int J Microcirc Clin Exp 15 (Suppl): 9–16

    Article  PubMed  Google Scholar 

  14. Hernandez LA, Grisham MB, Twohig B, Arfors KE, Harlan JM, Granger DN (1987) Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol 253: H699–H703

    PubMed  CAS  Google Scholar 

  15. Korthuis RJ, Grisham MB, Granger DN (1988) Leukocyte depletion attenuates vascular injury in post-ischemic skeletal muscle. Am J Physiol 254: H823–H827

    PubMed  CAS  Google Scholar 

  16. Granger DN, Benoit JN, Suzuki M, Grisham MB (1989) Leukocyte adherence to venular endothelium during ischemia-reperfusion. Am J Physiol 257: G683–G688

    PubMed  CAS  Google Scholar 

  17. Lehr HA, Guhlmann A, Nolte D, Keppler D, Messmer K (1991) Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster. J Clin Invest 87: 2036–2041

    Article  PubMed  CAS  Google Scholar 

  18. Granger DN, Kubes P (1994) The microcirculation and inflammation: modulation of leukocyte/endothelial cell adhesion. J Leukoc Biol 55: 662–675

    PubMed  CAS  Google Scholar 

  19. Klausner JM, Paterson IS, Valeri CR, Shepri D, Hechtman HB (1988) Limb ischemia-induced increase in permeability is mediated by leukocytes and leukotrienes. Ann Surg 208: 755–760

    Article  PubMed  CAS  Google Scholar 

  20. Belkin M, LaMorte ML, Wright JG, Hobson RW (1989) The role of leukocytes in the pathophysiology of skeletal muscle ischemic injury. J Vasc Surg 10: 14–17

    PubMed  CAS  Google Scholar 

  21. Carden DL, Smith JK, Korthuis RJ (1990) Neutrophil-mediated microvascular dysfunction in post-ischemic canine skeletal muscle. Role of granulocyte adherence. Circ Res 66: 1436–1444

    PubMed  CAS  Google Scholar 

  22. Jerome SN, Akimitsu T, Korthuis RJ (1994) Leukocyte adhesion, edema, and development of post-ischemic capillary no-reflow. Am J Physiol 267: H1329–H1336

    PubMed  CAS  Google Scholar 

  23. Nolte D, Hecht R, Schmid P, Botzlar A, Menger MD, Neumüller C, Sinowatz F, Vestweber D, Messmer K (1994) Role of Mac-1 and ICAM-1 in ischemia-reperfusion injury in a microcirculation model of BALB/C mice. Am J Physiol 267: H1320–H1328

    PubMed  CAS  Google Scholar 

  24. Maroko RP, Carpenter CB, Chiariello M, Fishbein MC, Radvany P, Knostman JD, Hale SL (1978) Reduction of cobra venom factor of myocardial necrosis after coronary artery occlusion. J Clin Invest 61: 661–670

    Article  PubMed  CAS  Google Scholar 

  25. Kubes P, Ibbotson G, Russell J, Wallace JL, Granger DN (1990) Role of platelet-activating factor in ischemia/reperfusion-induced leukocyte adherence. Am Physiol 259: G300–G305

    CAS  Google Scholar 

  26. Korthuis RJ, Granger DN, Townsley MI, Taylor AE (1985) The role of oxygen free radicals in ischemia-induced increases in canine skeletal muscle vascular permeability. Circ Res 57: 599–609

    PubMed  CAS  Google Scholar 

  27. Suzuki M, Inauen W, Kvietys RP, Grisham MB, Meininger C, Schelling ME, Granger HJ, Granger DN (1989) Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions. Am J Physiol 257: H1740–H1745

    PubMed  CAS  Google Scholar 

  28. Takenaka M, Tatsukawa Y, Dohi K, Ezaki H, Matsukawa K, Kawasaki T (1981) Protective effects of alpha-tocopherol and coenzyme Q10 on warm ischemic damages in the rat kidney. Transplantation 32: 137–141

    Article  PubMed  CAS  Google Scholar 

  29. Cho YW, Terasaki PI, Graver B (1989) Fifteen-year kidney graft survival. In: Terasaki P (ed) Clinical Transplants 1989. Los Angeles UCLA Tissue Typing Laboratory, pp 325–331

    Google Scholar 

  30. Foster MC, Wenham PW, Rowe PA, Burden RP, Morgan AG, Cotton RE, Blarney RW (1989) The late results of renal transplantation and the importance of chronic rejection as a cause of graft loss. Ann R Coll Surg Engl 71: 44–47

    PubMed  CAS  Google Scholar 

  31. Halloran P, Aprile MA, Farewell V, Ludwin D, Smith EK, Tsai SY, Bear RA, Cole EH, Fenton SS, Cattran DC (1988) Factors influencing early renal function in cadaver kidney transplants. Transplantation 45: 122–127

    Article  PubMed  CAS  Google Scholar 

  32. Van Es A, Hermans J, Van Bockel JH, Persijn GG, van Hooff JP, de Graeff J (1983) Effect of warm ischemia time and HLA (A and B ) matching on renal cadaveric graft survival and rejection episodes. Transplantation 36: 255–258

    Article  PubMed  Google Scholar 

  33. Matas A, Gillingham KJ, Sutherland DER (1993) Half-life and risk factors for kidney transplant outcome — importance of death with function. Transplantation 55: 757–761

    Article  PubMed  CAS  Google Scholar 

  34. Gaudin PB, Rayburn BK, Hutchins GM, Kasper EK, Baugham KL, Goodman SN, Lecks LE, Baumgartner WA, Hruban RH (1994) Peritransplant injury to the myocardium associated with the development of accelerated arteriosclerosis in heart transplant recipients. Am J Surg Pathol 18: 338–346

    Article  PubMed  CAS  Google Scholar 

  35. Scoazec JY, Durnad F, Degott C, Delautier D, Bernuau J, Belghiti J, Benhamou JP, Feldmann G (1994) Expression of cyclosporine-dependent adhesion molecules in post-reperfusion biopsy specimens of liver antigens. Gastroenterology 107: 1094–1102

    PubMed  CAS  Google Scholar 

  36. Briscoe DM, Yeung AC, Schoen FJ, Allred EN, Stavrakis G, Ganz P, Cotran RS, Pober JS, Schoen EL (1995) Predictive value of inducible endothelial cell adhesion molecule expression for acute rejection of human cardiac allografts. Transplantation 59: 204–211

    PubMed  CAS  Google Scholar 

  37. Cosimi AB, Conti D, Delmonico FL, Preffer FI, Wee SL, Rothlein R, Faanes R, Colvin RB (1990) In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol 144: 4604–4612

    PubMed  CAS  Google Scholar 

  38. Imaizumi T (1994) Effect of antibodies against neutrophil and endothelial adhesion molecules on reperfusion injury after pulmonary ischemia. Transplant Proc 26: 1851–1854

    PubMed  CAS  Google Scholar 

  39. Slocum MM, Granger DN (1993) Early mucosal and microvascular changes in feline intestinal transplants. Gastroenterology 105: 1761–1768

    PubMed  CAS  Google Scholar 

  40. Isobe M, Yagita H, Okumura K, Ihara A (1993) Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 255: 1125–1127

    Article  Google Scholar 

  41. Haug CE, Colvin RB, Delmonico FL, Auchincloss H, Tolkoff-Rubin N, Preffer FI, Rothlein R, Norris S, Scharschmidt L, Cosimi AB (1993) A phase I trial on immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients. Transplantation 55: 766–773

    Article  PubMed  CAS  Google Scholar 

  42. Marzi I, Knee J, Buhren V, Menger M, Trentz O (1992) Reduction by superoxide dismutase of leukocyte-endothelial cell adherence after liver transplantation. Surgery 111: 90–97

    PubMed  CAS  Google Scholar 

  43. Toledo-Pereyra LH, Simmons RL, Najarian JS (1975) Protection of the ischemic liver by donor pre-treatment before transplantation. J Surg Res 129: 513–517

    CAS  Google Scholar 

  44. Demirbas A, Bozoklu S, Özdemir A, Bilgin N, Haberal M (1993) Effect of alpha tocopherol on the prevention of reperfusion injury caused by free oxygen radicals in the canine kidney autotransplantation model. Transplant Proc 25: 2274

    PubMed  CAS  Google Scholar 

  45. Tanemoto K, Sakagami K, Orita K (1993) Beneficial effect of EPC-K1 on the survival of warm ischemic damaged graft in rat cardiac transplantation. Acta Med Okayama 47: 121–127

    PubMed  CAS  Google Scholar 

  46. Ikeda M, Sumimoto K, Urushihara T, Fukuda Y, Dohi K, Kawasaki T (1994) Prevention of ischemic damage in rat pancreatic transplantation by pretreatment with alpha tocopherol. Transplant Proc 26: 561–562

    PubMed  CAS  Google Scholar 

  47. Rao PN, Walsh TR, Makowka L, Liu T, Demitris AJ, Rubin RS, Snyder JT, Mischinger HJ, Starzl TE (1990) Inhibition of free radical generation and improved survival by protection of the hepatic microvascular endothelium by targeted erythrocytes in orthotopic liver transplantation. Transplantation 49: 1055–1059

    Article  PubMed  CAS  Google Scholar 

  48. Oda T, Nakai I, Mituo M, Yamagashi H, Oka T, Yoshikawa Y (1992) Role of oxygen radicals and synergistic effect of superoxide dismutase and catalase on ischemia-re-perfusion injury of the rat pancreas. Transplant Proc 24: 797–798

    PubMed  CAS  Google Scholar 

  49. Slakey D, Roza A, Pieper G, Johnson C, Adams M (1993) Ascorbic acid and alpha tocopherol prolong rat cardiac allograft survival. Transplant Proc 25: 610–611

    PubMed  CAS  Google Scholar 

  50. Rabl H, Khoschsorur G, Colombo T, Petritsch P, Rauchenwald M, Költringer P, Tatzber F, Esterbauer H (1993) A multivitamin infusion prevents lipid peroxidation and improves transplantation performance. Kidney Int 43: 912–917

    Article  PubMed  CAS  Google Scholar 

  51. Shackleton CR, Ettinger SL, McLoughlin MC, Scudamore CH, Miller RR, Keown PA (1990) Effect of recovery from ischemia injury on class I and class II MHC antigen expression. Transplantation 49: 641–644

    Article  PubMed  CAS  Google Scholar 

  52. Shoskes DA, Parfrey NA, Halloran PF (1990) Increased major histocompatibility complex antigen expression in unilateral ischemia acute tubular necrosis in the mouse. Transplantation 49: 201–207

    Article  PubMed  CAS  Google Scholar 

  53. Adoumie R, Serrick C, Giaid A, Shennib H (1992) Early cellular events in the lung allograft. Ann Thorac Surg 54: 1071–1076

    Article  PubMed  CAS  Google Scholar 

  54. Bishop GA, Waugh JA, Hall BM (1988) Expression of HLA antigens on renal tubular cells in culture: II. Effect of increased HLA antigen expression on tubular cell stimulation of lymphocyte activation and on their vulnerability to cell-mediated lysis. Transplantation 46: 303–310

    Article  PubMed  CAS  Google Scholar 

  55. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87: 1620–1624

    Article  PubMed  CAS  Google Scholar 

  56. Dusting GJ (1995) Nitric oxide in cardiovascular disorders. J Vasc Res 32: 143–161

    Article  PubMed  CAS  Google Scholar 

  57. Kubes P, Kanwar S, Niu XF, Gaboury J (1993) Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. FASEB J 7: 1293–1299

    PubMed  CAS  Google Scholar 

  58. Langher JM, Hoffman R, Lancaster JR, Simmons R (1993) Nitric oxide — a new endogenous immunomodulator. Transplantation 55: 1205–1212

    Article  Google Scholar 

  59. Langher JM, Dull KE, Ochoa J, Billiar T, Ildstad S, Schaut W, Simmons R, Hoffman R (1992) Evidence that nitric oxide production in in vivo allosensitized cells inhibits the development of allospecific CTL. Transplantation 53: 632–640

    Article  Google Scholar 

  60. Mills GD (1991) Molecular basis of “suppressor” macrophages. Arginine metabolism via the nitric oxide synthase pathway. J Immunol 146: 2719–2723

    PubMed  CAS  Google Scholar 

  61. Häyry P, Isoniemi H, Yilmaz S, Mennander A, Lernstrom K, Räisänen-Sokolowski A, Koskinen P, Ustinov J, Lautenschlager I, Taskinen E (1993) Chronic allograft rejection. Immunol Rev 134: 33–81

    Article  PubMed  Google Scholar 

  62. Azuma H, Tilney NL (1994) Chronic graft rejection. Curr Opin Immunol 6: 770–776

    Article  PubMed  CAS  Google Scholar 

  63. Fellström (1995) Vascular mechanisms in the development of chronic rejection. Prog Appl Microcirc 21: 92–99

    Google Scholar 

  64. Ross R (1993) Atherosclerosis: a defense mechanism gone awry. Am J Pathol 143: 987–1002

    PubMed  CAS  Google Scholar 

  65. Poston RN, Haskard DO, Coucher JR, Gall NP, Johnson-Tidey RR (1992) Expression of intracellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 140: 665–673

    PubMed  CAS  Google Scholar 

  66. Azuma H, Heemann UW, Tillius SG, Tilney NL (1994) Cytokines and adhesion molecules in chronic rejection. Clin Transplant 8: 168–180

    PubMed  CAS  Google Scholar 

  67. Gimbrone MA (1995) Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol 75: 67B–70B

    Article  PubMed  CAS  Google Scholar 

  68. Duijvestijn A, Kok M, Miyasaka M, Vriesman PV (1993) ICAM-1 and LFA-1/CD18 expression in chronic renal allograft rejection. Transplant Proc 25: 2867–2868

    PubMed  CAS  Google Scholar 

  69. Rao GN, Berk BC (1992) Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. Circ Res 70: 593–599

    PubMed  CAS  Google Scholar 

  70. Häyry P, Alatalo S, Myllärniemi M, Räisänen-Sokolowski A, Lernström K (1995) Cellular and Molecular Biology of chronic rejection. Transplant Proc 27: 71–74

    PubMed  Google Scholar 

  71. Vender RL, Clemmons DR, Kwock L, Friedman M (1987) Reduced oxygen tension induces pulmonary endothelium to release pulmonary smooth muscle cell mitogen(s). Am Rev Respir Dis 135: 622–627

    PubMed  CAS  Google Scholar 

  72. Hassoun PM, Pasricha PJ, Teufel E, Lee SL, Fanburg BL (1989) Hypoxia stimulates the release by bovine pulmonary artery endothelial cells of an inhibitor of pulmonary artery smooth muscle cell growth. Am J Respir Cell Mol Biol 1: 377–384

    PubMed  CAS  Google Scholar 

  73. Michiels C, De Leener F, Arnould T, Dieu M, Remacle J (1994) Hypoxia stimulates human endothelial cells to release smooth muscle cell mitogens: role of prostaglandins and bFGF. Exp Cell Res 213: 43–54

    Article  PubMed  CAS  Google Scholar 

  74. Yilmaz S, Paavonen T, Häyry P (1992) Chronic rejection of rat kidney allografts. II. The impact of prolonged ischemia on transplant histology. Transplantation 53: 823–827

    Article  PubMed  CAS  Google Scholar 

  75. Tullius SG, Heemann U, Hancock WW, Azuma H, Tilney NL (1994) Long-term kidney isografts develop functional and morphologic changes that mimic those of chronic allograft rejection. Ann Surg 220: 425–435

    Article  PubMed  CAS  Google Scholar 

  76. Wanders A, Akyürek MI, Waltenberger J, Ren ZP, Stafberg C, Funa K, Larsson E, Fellström B (1995) Ischemia-induced transplant arteriosclerosis in the rat. Arterioscler Thromb Vasc Biol 15: 145–155

    PubMed  CAS  Google Scholar 

  77. Land W, Schneeberger H, Schleibner S, Illner WD, Abendroth D, Rutili G, Arfors KE, Messmer K (1994) The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants. Transplantation 57: 211–217

    Article  PubMed  CAS  Google Scholar 

  78. Schneeberger H, Illner WD, Abendroth D, Bulkley G, Rutili F, Williams M, Thiel M, Land W (1989) First clinical experience with superoxide dismutase in kidney transplantation: results of a double-blind randomized study. Transplant Proc 121: 1245–1246

    Google Scholar 

  79. Marubayashi S, Dohi K, Sunimoto K, Oku J, Ochi K, Kawasaki T (1989) Changes in activity of oxygen free radical scavengers and in levels of endogenous antioxidants during hepatic ischemia and subsequent reperfusion. Transplant Proc 21: 1317–1318

    PubMed  CAS  Google Scholar 

  80. Serino F, Citterio F, Lippa S, Oradei A, Agnes S, Nanni G, Pozzetto A, Littarru G, Castagneto M (1990) Coenzyme Q, alpha tocopherol and delayed function in human kidney transplantation. Transplant Proc 22: 1375–1378

    PubMed  CAS  Google Scholar 

  81. Goode HF, Webster NR, Howdle PD, Leek JP, Lodge JPA, Sadek SA, Walker BE (1994) Reperfusion injury, antioxidants and hemodynamics during orthotopic liver transplantation. Hepatology 19: 354–359

    Article  PubMed  CAS  Google Scholar 

  82. Princemail J, Defraigne JO, Franssen C, Bonnet P, Deby-Dupont G, Pirenne J, Deby C, Lamy M, Limet M, Meurisse M (1993) Evidence for free radical formation during human kidney transplantation. Free Radic Biol Med 15: 343–348

    Article  Google Scholar 

  83. Riemersma RA, Wood DA, Macintyre CCA, Elton RA, Gey KF, Oliver MF (1991) Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene. Lancet 337: 1–5

    Article  PubMed  CAS  Google Scholar 

  84. Enstrom JE, Kanim LE, Klein MA (1992) Vitamin C intake and mortality among a sample of the United States population. Epidemiology 3: 194–202

    Article  PubMed  CAS  Google Scholar 

  85. Gey KF, Moser UK, Jordan P, Stählin HB, Eichholzer M, Lüdin E (1993) Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiologic update with special attention to carotene and vitamin C. Am J Clin Nutr 57 (Suppl): 787S–797S

    PubMed  CAS  Google Scholar 

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Lehr, HA., Messmer, K. (1997). Role of Ischemia/Reperfusion Injury in Organ Transplantation. In: Schultheiss, HP., Schwimmbeck, P. (eds) The Role of Immune Mechanisms in Cardiovascular Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60463-8_15

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  • DOI: https://doi.org/10.1007/978-3-642-60463-8_15

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