Myocardial Protection From Reperfusion Injury With Adenosine

  • Jakob Vinten-Johansen
  • Zhi-Qing Zhao
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 194)


Adenosine has recently been moved into the limelight for its clinically applicable physiological effects. Certainly, its cardiovascular effects have long been recognized,1 and its vasodilator effects have been proposed as a central mechanism of autoregulation of coronary blood flow.2 In addition, its negative inotropic and chronotropic effects have been understood for many years.3,4 However, it has not been until the last decade that adenosine has been appreciated for its cardioprotective potential against ischemic-reperfusion injury. Since the observations of Olafsson et al,5 there has been a virtual explosion of research focused on unraveling the mechanisms by which this endogenous autacoid protects the heart from non-lethal as well as lethal injury after ischemia and reperfusion. As investigative efforts have progressed, the temporal dynamics and mechanisms by which adenosine exerts cardioprotection have become more intriguing, and more complex. Adenosine has potential to exert cardioprotection during all three windows of cardioprotection (pretreatment or preconditioning, ischemia and reperfusion). Therefore, adenosine has emerged as a broad-spectrum cardioprotective agent that exerts protection endogenously as well as by pharmacological application (exogenously). However, the observation of adenosine as protagonist of injury by its stimulation of neutrophil-mediated events, a provider of substrate for enhanced generation of superoxide anions via xanthine oxidase of its metabolites xanthine and hypoxanthine, and antagonist to injury via numerous mechanisms offers an intriguing challenge to investigators to elucidate its entire spectrum of physiological and molecular effects. During which of these windows adenosine exerts its effects on the participants in the injury processes will determine its optimal therapeutic use.6 This chapter will focus on the mechanisms of myocardial protection by endogenous and exogenous adenosine, and receptor-specific analogs with specific reference to mechanisms involved in reperfusion injury; a full discussion of adenosine regulating agents is beyond its scope.


Infarct Size Reperfusion Injury Myocardial Protection Myocardial Stunning Blood Cardioplegia 
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.
    Drury AN, Szent-Györgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol (Lond) 1929;68:213–237.Google Scholar
  2. 2.
    Berne RM, Knabb RM, Ely SW, et al. Adenosine in the local regulation of blood flow: a brief overview. Fed Proc 1983;42:3136–3142.PubMedGoogle Scholar
  3. 3.
    Belardinelli L, West A, Crampton R, et al. Chronotropic and dromotropic actions of adenosine. In: Berne RM, Rall TW, Rubio R, eds. The regulatory function of adenosine. The Hague: Martinus Nijhoff, 1983:378–398.Google Scholar
  4. 4.
    Froldi G, Belardinelli L. Species-dependent effects of adenosine on heart rate and atrioventricular nodal conduction. Mechanism and physiological implications. Circ Res 1990;67:960–978.PubMedCrossRefGoogle Scholar
  5. 5.
    Olafsson B, Forman MB, Puett DW, et al. Reduction of reperfusion injury in the canine preparation by intracoronary adenosine: importance of the endothelium and the no-reflow phenomenon. Circulation 1987;76:1135–1145.PubMedCrossRefGoogle Scholar
  6. 6.
    Vinten-Johansen J, Hammon JW, (jrJr.) Cardioprotection by adenosine: Is it a question of effective dose, timing, or the target compartment? Letters to the editor. J Thorac Cardiovasc Surg 1996;112:202–204.PubMedCrossRefGoogle Scholar
  7. 7.
    Van Wylen DGL. Relationship between intracoronary adenosine, interstitial fluid purine metabolites, and coronary blood flow. Drug Devel Res 1994;31:330Google Scholar
  8. 8.
    Cronstein BN, Kramer SB, Weissmann G, et al. Adenosine: a physiological modulator of superoxide anion generation by human neutrophils. J Exp Med 1983;158:1160–1177.PubMedCrossRefGoogle Scholar
  9. 9.
    Kitakaze M, Hori M, Sato H, et al. Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs. Circ Res 1991;69:1402–1408.PubMedCrossRefGoogle Scholar
  10. 10.
    Colli S, Tremoli E. Multiple effects of dipyridamole on neutrophils and mononuclear leukocytes: adenosine-dependent and adenosine-independent mechanisms. J Lab Clin Med 1991;118:136–145.PubMedGoogle Scholar
  11. 11.
    Mullane K. Neutrophil and endothelial changes in reperfusion injury. Trends Cardiovasc Med 1991;l:282–289.CrossRefGoogle Scholar
  12. 12.
    Dreyer WJ, Michael LH, West MW, et al. Neutrophil accumulation in ischemic canine myocardium: Insights into time course, distribution, and mechanism of localization during early reperfusion. Circulation 1991;84:400–411.PubMedCrossRefGoogle Scholar
  13. 13.
    Lucchesi BR, Werns SW, Fantone JC. The role of neutrophils and free radicals in ischemic myocardial injury. J Mol Cell Cardiol 1989;21:1241–1251.PubMedCrossRefGoogle Scholar
  14. 14.
    Mullane KM. Myocardial ischemia-reperfusion injury: Role of neutrophils and neutrophil-derived mediators. In: Marone G, Lichtestein L, Condorelly M, Fauci AS, eds. Human Inflammatory Disease: Clinical Immunology. 1st ed. Toronto: Decker, Inc. 1988:143Google Scholar
  15. 15.
    Mehta JL, Nichols WW, Mehta P. Neutrophils as potential participants in acute myocardial ischemia: Relevance to reperfusion. J Am Coll Cardiol 1988; 11:1309–1316.PubMedCrossRefGoogle Scholar
  16. 16.
    Roberts PA, Newby AC, Hallett MB, et al. Inhibition by adenosine of reactive oxygen metabolite production by human polymorphonuclear leucocytes. Biochem J 1985:227:669–674.PubMedGoogle Scholar
  17. 17.
    Cronstein BN, Rosenstein ED, Kramer SB, et al. Adenosine: a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 1985;135:1366–1371.PubMedGoogle Scholar
  18. 18.
    Cronstein BN, Levin RI, Belanoff J, et al. Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endotheiial cells. J Clin Invest 1986;78:760–770.PubMedCrossRefGoogle Scholar
  19. 19.
    Wollner A, Wollner S, Smith JB. Acting via A2 receptors, adenosine inhibits the upregulation of Mac-1 (CD11 b/CD 18) expression on FMLP-stimulated neutrophils. Am J Resp Cell & Mol Biol 1993;9:179–185.Google Scholar
  20. 20.
    Gruber HE, Hoffer ME, McAllister DR, et al. Increased adenosine concentration in blood from ischemic myocardium by AICA Riboside. Effects on flow, granulocytes, and injury. Circulation 1989;80:1400–14U.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhao Z-Q, Sato H, Williams MW, et al. Adenosine A2-Receptor Activation Inhibits Neutrophil-Mediated Injury to Coronary Endothelium. Am J Physiol 1996;271;H1456–1464.PubMedGoogle Scholar
  22. 22.
    Nolte D, Lorenzen A, Lehr HA, et al. Reduction of postischemic leukocyte-endothelium interaction by adenosine via A2 receptor. Naunyn-Schmiedebergs Archives of Pharmacology 1992;346.234–237.CrossRefGoogle Scholar
  23. 23.
    Nolte D, Lehr HA, Messmer K. Adenosine inhibits postischemic leukocyte-endothelium interaction in postcapillary venules of the hamster. Am J Physiol 1991;261:H651–5.PubMedGoogle Scholar
  24. 24.
    Williams MW, Jordan JE, Fernandez AZ, et al. Adenosine (ADO) inhibits unactivated neutrophil (PMN) adherence to thrombin stimulated coronary vascular endothelium (EC) by a p-selectin mechanism. FASEB J 1996; 10:A280(Abstract)Google Scholar
  25. 25.
    Fernandez AZ, Williams MW, Jordan JE, et al. Neutrophil (PMN) adherence to thrombin stimulated coronary vascular endothelium is inhibited by an adenosine (ADO) A2-receptor mechanism. FASEB J 1996;10:A611(Abstract)Google Scholar
  26. 26.
    Zahler S, Becker BF, Raschke P, et al. Stimulation of endothelial adenosine A1, receptors enhances adhesion of neutrophils in the intact guinea pig coronary system. Cardiovasc Res 1994;28:1366–1372.PubMedCrossRefGoogle Scholar
  27. 27.
    Raschke P, Becker BF. Adenosine and PAF dependent mechanisms lead to myocardial reperfusion injury by neutrophils after brief ischaemia. Cardiovasc Res 1995;29:569–576.PubMedGoogle Scholar
  28. 28.
    Gunther GR, Herring MB. Inhibition of neutrophil superoxide production by adenosine released from vascular endothelial cells. Ann Vase Surg 1991;5:325–330.CrossRefGoogle Scholar
  29. 29.
    Hoffmeister HM, Mauser M, Schaper W. Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium. Bas Res Cardiol 1985;80:445–458.CrossRefGoogle Scholar
  30. 30.
    Ambrosio G, Jacobus WE, Mitchell MC, et al. Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts. Am J Physiol 1989;256:H560–H566.PubMedGoogle Scholar
  31. 31.
    Sekili S, Jeroudi MO, Tang X, et al. Effect of adenosine on myocardial’ stunning’ in the dog. Circ Res 1995;76:82–94.PubMedCrossRefGoogle Scholar
  32. 32.
    Randhawa MPS, (jrJr.), Lasley RD, Mentzer RM, (jrJr.) Salutary effects of exogenous adenosine administration on in vivo myocardial stunning. J Thorac Cardiovasc Surg 1995; 110:63–74.PubMedCrossRefGoogle Scholar
  33. 33.
    Jeroudi MO, Tang X-L, Abd-Elfattah AS, et al. Effect of adenosine A1,-receptor activation on myocardial stunning in intact dogs. Circulation 1994;90 (No 4, Part 2):I–479(Abstract)Google Scholar
  34. 34.
    Lasley RD, Rhee JW, Van Wylen DGL, et al. Adenosine A1, receptor mediated protection of the globally ischemic isolated rat heart. J Mol Cell Cardiol 1990;22:39–47.PubMedCrossRefGoogle Scholar
  35. 35.
    Lasley RD, Mentzer RM. Adenosine improves recovery of postischemic myocardial function via an adenosine A1, receptor mechanism. Am J Physiol 1992;263:H1460–H1465.PubMedGoogle Scholar
  36. 36.
    Lasley RD, Mentzer RM, (jrJr.) Protective effects of adenosine in the reversibly injured heart. Ann Thorac Surg 1995;60:843–846.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhou Z, Bunger R, Lasley RD, et al. Adenosine pretreatment increases cytosolic phosphorylation potential and attenuates postischemic cardiac dysfunction in swine. Surg Forum 1993;249–251.Google Scholar
  38. 38.
    Janier MF, Vanoverschelde JJ, Bergmann SR. Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms. Am J Physiol 1993;264:H163–H170.PubMedGoogle Scholar
  39. 39.
    Bolli R. Role of neutrophils in myocardial stunning after brief ischaemia: the end of a six year old controversy (1987-1993) [comment]. Cardiovasc Res 1993;27:728–730.PubMedCrossRefGoogle Scholar
  40. 40.
    Juneau CF, Ito BR, del Balzo U, et al. Severe neutrophil depletion by leucocyte filters or cytotoxic drug does not improve recovery of contractile function in stunned porcine myocardium [see comments]. Cardiovasc Res 1993;27:720–727.PubMedCrossRefGoogle Scholar
  41. 41.
    Reimer KA, Jennings RB. The “wavefront phenomenon ” of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardial at risk) and collateral flow. Lab Invest 1979;40:633–644.PubMedGoogle Scholar
  42. 42.
    Ma X, Tsao PS, Viehman GE, et al. Neutrophil-mediated vasoconstriction and endothelial dysfunction in low-flow perfusion-reperfused cat coronary artery. Circ Res 1991;69:95–106.PubMedCrossRefGoogle Scholar
  43. 43.
    Ma X, Weyrich AS, Lefer DJ, et al. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res 1993;72:403–412.PubMedCrossRefGoogle Scholar
  44. 44.
    Lefer AM, Tsao PS, Lefer DJ, et al. Role of endothelial dysfunction in the pathogenesis of reperfusion injury after myocardial ischemia. FASEB J 1991;5:2029–2034.PubMedGoogle Scholar
  45. 45.
    Siminiak T, Ozawa T. Neutrophil mediated myocardial injury. [Review]. International Journal of Biochemistry 1993;25:147–156.PubMedCrossRefGoogle Scholar
  46. 46.
    Pitarys CJ, Virmani R, Vildibill HD, (jrJr.), et al. Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 1991;83:237–247.PubMedCrossRefGoogle Scholar
  47. 47.
    Norton ED, Jackson EK, Turner MB, et al. The effects of intravenous infusions of selective adenosine A1,-receptor and A2-receptor agonists on myocardial reperfusion injury. Am Heart J 1992;123:332–338.PubMedCrossRefGoogle Scholar
  48. 48.
    Babbitt DG, Virmani R, Fortran MB. Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model. Circulation 1989;80:1388–1399.PubMedCrossRefGoogle Scholar
  49. 49.
    Homeister JW, Hoff PT, Fletcher DD, et al. Combined adenosine and lidocaine administration limits myocardial reperfusion injury. Circulation 1990;82:595–608.PubMedCrossRefGoogle Scholar
  50. 50.
    Goto M, Miura T, Iliodoromitis EK, et al. Adenosine infusion during early reperfusion failed to limit myocardial infarct size in a collateral deficient species. Cardiovasc Res 1991;25:943–949.PubMedCrossRefGoogle Scholar
  51. 51.
    Toombs CF, McGee DS, Johnston WE, et al. Protection from ischaemic-reperfusion injury with adenosine pretreatment is reversed by inhibition of ATP-sensitive potassium channels. Cardiovasc Res 1993;27:623–629.PubMedCrossRefGoogle Scholar
  52. 52.
    Vinten-Johansen J, Lefer DJ, Nakanishi K, et al. Controlled coronary hydrodynamics at the time of reperfusion reduces postischemic injury. Cor Art Dis 1992;3:1081–1093.CrossRefGoogle Scholar
  53. 53.
    Zhao Z-Q, Nakanishi K, McGee DS, et al. A1-receptor mediated myocardial infarct size reduction by endogenous adenosine is exerted primarily during ischemia. Cardiovasc Res 1994;28:270–279.PubMedCrossRefGoogle Scholar
  54. 54.
    Jordan JE, Zhao Z-Q, Sato H, et al. Adenosine A2 activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence. J Pharmacol Exp Ther 1996Google Scholar
  55. 55.
    Schlack W, Schäfer M, Uebing A, et al. Adenosine A2-receptor activation at reperfusion reduces infarct size and improves myocardial wall function in dog heart. J Cardiovasc Pharmacol 1993;22:89–96.PubMedCrossRefGoogle Scholar
  56. 56.
    Cronstein BN, Daguma L, Nichols D, et al. The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively. J Clin Invest 1990;85:1150–1157.PubMedCrossRefGoogle Scholar
  57. 57.
    Nees S. Coronary flow increases induced by adenosine and adenine nucleotides are mediated by the coronary endothelium: a new principle of the regulation of coronary flow. Eur Heart J 1989;10:28-35.Google Scholar
  58. 58.
    Balcells E, Suarez J, Rubio R. Functional role of intravascular coronary endothelial adenosine receptors. Eur J Pharmacol 1992;210:l–9.CrossRefGoogle Scholar
  59. 59.
    Todd JC, Zhao Z-Q, Williams MW, et al. Intravascular adenosine at reperfusion reduces infarct size and neutrophil adherence. Ann Thorac Surg 1996;62;1364–1372.PubMedCrossRefGoogle Scholar
  60. 60.
    Headrick JP, Berne RM. Endothelium-dependent and-independent relaxations to adenosine in guinea pig aorta. Am J Physiol 1990;259:H62–H67.PubMedGoogle Scholar
  61. 61.
    Woolfson RG, Patel VC, Neild GH, et al. Inhibition of nitric oxide synthesis reduces infarct size by an adenosine-dependent mechanism. Circulation 1995;91:1545–1551.PubMedCrossRefGoogle Scholar
  62. 62.
    Hasebe N, Shen Y-T, Vatner SF. Inhibition of endothelium-derived relaxing factor enhances myocardial stunning in conscious dogs. Circulation 1993;88:2862–2871.PubMedCrossRefGoogle Scholar
  63. 63.
    Khatchikian6GS, Mikhail EA, Zweier JL, et al. Role of endogenous adenosine in protecting against neutrophil-mediated injury in postischemic hearts. Circulation 1996;92:I–712(Abstract)Google Scholar
  64. 64.
    Liu GS, Thornton J, Van Winkle DM, et al. Protection against infarction afforded by preconditioning is mediated by A1, adenosine receptors in rabbit hearts. Circulation 1991;84:350–356.PubMedCrossRefGoogle Scholar
  65. 65.
    Tsuchida A, Miura T, Miki T, et al. Role of adenosine receptor activation in myocardial infarct size limitation by ischaemic preconditioning. Cardiovasc Res 1992;26:456–461.PubMedCrossRefGoogle Scholar
  66. 66.
    Toombs CF, McGee DS, Johnston WE, et al. Myocardial protective effects of adenosine: Infarct size reduction with pretreatment and continued receptor stimulation during ischemia. Circulation 1992;86:986–994.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhao Z-Q, McGee DS, Nakanishi K, et al. Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit. Circulation 1993;88:709–719.PubMedCrossRefGoogle Scholar
  68. 68.
    Pearson JD, Carleton JS, Hutchings A, et al. Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture. Biochem J 1978;170:265–271.PubMedGoogle Scholar
  69. 69.
    Deussen A, Bading B, Kelm M, et al. Formation and salvage of adenosine by macrovascular endothelial cells. Am J Physiol 1993;264:H692–H700.PubMedGoogle Scholar
  70. 70.
    Smolenski RT, Kochan Z, McDouall R, et al. Endothelial nucleotide catabolism and adenosine production. Cardiovasc Res 1994;28:100–104.PubMedCrossRefGoogle Scholar
  71. 71.
    Deussen A, Möser G, Schrader J. Contribution of coronary endothelial cells to cardiac adenosine production. Pflug Archiv 1986;406:608–614.CrossRefGoogle Scholar
  72. 72.
    Borst MM, Schrader J. Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine. Circ Res 1991;68:797–806.PubMedCrossRefGoogle Scholar
  73. 73.
    van Waeg G, Van den Berghe G. Purine Catabolism in Polymorphonuclear Neutrophils: Phorbol myristate acetate-induced accumulation of adenosine owing to inactivation of extracellularly released adenosine deaminase. J Clin Invest 1991;87:305–312.PubMedCrossRefGoogle Scholar
  74. 74.
    Kitakaze M, Hori M, Morioka T, et al. Attenuation of ecto-5’-nucleotidase activity and adenosine release in activated human polymorphonuclear leukocytes. Circ Res 1993;73:524–533.PubMedCrossRefGoogle Scholar
  75. 75.
    Vinten-Johansen J, Hammon JW, (jrJr.) Myocardial Protection During Cardiac Surgery. In: Utley J, Gravlee GP, eds. Cardiopulmonary Bypass: Principles and Practice. New York: Williams &Wilkins, 1993:155–206.Google Scholar
  76. 76.
    Vinten-Johansen J, Nakanishi K. Postcardioplegia acute cardiac dysfunction and reperfusion injury. [Review]. J Cardiothorac Vasc Anesth 1993;7:6–18.PubMedCrossRefGoogle Scholar
  77. 77.
    Gayheart PA, Vinten-Johansen J, Johnston WE, et al. Oxygen requirements of the dyskinetic myocardial segment. Am J Physiol 1989;257:H1184–H1191.PubMedGoogle Scholar
  78. 78.
    Allen BS, Rosenkranz ER, Buckberg GD, et al. Studies of controlled reperfusion after ischemia. VII. High oxygen requirements of dyskinetic cardiac muscle. J Thorac Cardiovasc Surg 1986;92:543–552.PubMedGoogle Scholar
  79. 79.
    Buckberg GD. Myocardial protection: An overview. Semin Thorac Cardiovasc Surg 1993;5:98–106.PubMedGoogle Scholar
  80. 80.
    Galiňianes M, Chambers DJ, Hearse DJ. Should adenosine continue to be ignored as a cardioprotective agent in cardiac operations? J Thorac Cardiovasc Surg 1993;105:180-183.Google Scholar
  81. 81.
    Woolfson RG, Patel VC, Yellon DM. Pre-conditioning with adenosine leads to concentration-dependent infarct size reduction in the isolated rabbit heart. Cardiovasc Res 1996;31:148–151.PubMedGoogle Scholar
  82. 82.
    Jennings RB. Myocardial ischemia-observation, definitions, and speculations. J Mol Cell Cardiol 1970;l:345–349.CrossRefGoogle Scholar
  83. 83.
    Thornton JD, Liu GS, Olsson RA, et al. Intravenous pretreatment with A1,-selective adenosine analogues protects the heart against infarction. Circulation 1992;85:659–665.PubMedCrossRefGoogle Scholar
  84. 84.
    Randhawa MPS, Jr., Lasley RD, Mentzer, (jrJr.) Adenosine and the stunned heart. J Card Surg 1993;8(Suppl):332–337.PubMedGoogle Scholar
  85. 85.
    Friedrichs GS, Kilgore KS, Manley PJ, et al. Effects of heparin and N-Acetyl heparin on ischemia/reperfusion-induced alterations in myocardial function in the rabbit isolated heart. Circ Res 1994;75:701–710.PubMedCrossRefGoogle Scholar
  86. 86.
    Hearse DJ, Stewart DA, Braimbridge MV. Cellular protection during myocardial ischemia. The development and characterization of a procedure for the induction of reversible ischemic arrest. Circulation 1976;54:193–202.PubMedCrossRefGoogle Scholar
  87. 87.
    Schubert T, Vetter H, Owen P, et al. Adenosine cardioplegia: Adenosine versus potassium cardioplegia: Effects on cardiac arrest and postischemic recovery in the isolated rat heart. J Thorac Cardiovasc Surg 1989;98:1057–1065.PubMedGoogle Scholar
  88. 88.
    Thelin S, Hultman J, Ronquist G. Effects of adenosine infusion on the pig heart during normothermic ischemia and reperfusion. Scand J Thorac Cardiovasc Surg 1991;25:207–213.PubMedCrossRefGoogle Scholar
  89. 89.
    de Jong JW, van der Meer P, van Loon H, et al. Adenosine as adjunct to potassium cardioplegia: Effect on function, energy metabolism, and electrophysiology. J Thorac Cardiovasc Surg 1990;100:445–454.PubMedGoogle Scholar
  90. 90.
    Galiflanes M, Hearse DJ. Exogenous adenosine accelerates recovery of cardiac function and improves coronary flow after long-term hypothermic storage and transplantation. J Thorac Cardiovasc Surg 1992;104:151–158.Google Scholar
  91. 91.
    Fremes SE, Zhang J, Furukawa RD, et al. Cardiopulmonary bypass, myocardial management, and support techniques. Adenosine pretreatment for prolonged cardiac storage. An evaluation with St. Thomas’ Hospital and University of Wisconsin solutions. J Thorac Cardiovasc Surg 1995;110:293–301.PubMedCrossRefGoogle Scholar
  92. 92.
    Boiling SF, Bies LE, Bove EL, et al. Augmenting intracellular adenosine improves myocardial recovery. J Thorac Cardiovasc Surg 1990;99:469–474.Google Scholar
  93. 93.
    Boiling SF, Bies LE, Bove EL. Effect of ATP synthesis promoters on postischemic myocardial recovery. J Surg Res 1990;49:205–211.CrossRefGoogle Scholar
  94. 94.
    Ledingham S, Katayama 0, Lachno D, et al. Beneficial effect of adenosine during reperfusion following prolonged cardioplegic arrest. Cardiovasc Res 1990;24:247–253.PubMedCrossRefGoogle Scholar
  95. 95.
    Rosenkranz ER, Okamoto F, Buckberg GD, et al. Studies of controlled reperfusion after ischemia. II. Biochemical studies: failure of tissue adenosine triphosphate levels to predict recovery of contractile function after controlled reperfusion. J Thorac Cardiovasc Surg 1986;92:488–501.PubMedGoogle Scholar
  96. 96.
    Hohlfeld T, Hearse DJ, Yellon DM, et al. Adenosine-induced increase in myocardial ATP: Are there beneficial effects for the ischaemic myocardial? Bas Res Cardiol 1989;84:499–509.CrossRefGoogle Scholar
  97. 97.
    Hudspeth DA, Nakanishi K, Vinten-Johansen J, et al. Adenosine in blood cardioplegia prevents postischemic dysfunction in ischetnically injured hearts. Ann Thorac Surg 1994;58:1637–1644.PubMedCrossRefGoogle Scholar
  98. 98.
    Nakanishi K, Zhao Z-Q, Vinten-Johansen J, et al. Coronary artery endothelial dysfunction after ischemia, blood cardioplegia, and reperfusion. Ann Thorac Surg 1994;58:191–199.PubMedCrossRefGoogle Scholar
  99. 99.
    Dignan RJ, Dyke CM, Abd-Elfattah AS, et al. Coronary artery endothelial cell and smooth muscle dysfunction after global myocardial ischemia. Ann Thorac Surg 1992;53:311–317.PubMedCrossRefGoogle Scholar
  100. 100.
    Sellke FW, Friedman M, Wang SY, et al. Adenosine and AICA-riboside fail to enhance microvascular endothelial preservation. Ann Thorac Surg 1994;58:200–206.PubMedCrossRefGoogle Scholar
  101. 101.
    Nakanishi K, Zhao Z-Q, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg 1995;109:1146–1154.PubMedCrossRefGoogle Scholar
  102. 102.
    Sato H, Zhao Z-Q, McGee DS, et al. Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury. J Thorac Cardiovasc Surg 1995; 110:302–314.PubMedCrossRefGoogle Scholar
  103. 103.
    Boiling SF, Bies LE, Gallagher KP, et al. Enhanced myocardial protection with adenosine. Ann Thorac Surg 1989;47:809–815.CrossRefGoogle Scholar
  104. 104.
    Gottlieb RA, Burleson K.O, Kloner RA, et al. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 1994;94:1621–1628.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Jakob Vinten-Johansen
  • Zhi-Qing Zhao

There are no affiliations available

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