Adenosine Cardioprotection and Potential Mechanisms

  • Robert D. Lasley
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 194)


The purine nucleoside adenosine exerts numerous physiological effects in normal mammalian myocardium, including modulation of coronary blood flow and negative chronotropic, dromotropic, and anti-adrenergic properties. The cellular mechanisms of these effects have, for the most part, been well delineated.1 In the last several years it has been established that adenosine also exerts effects in ischemic and reperfused myocardium. Infusion of adenosine prior to ischemia enhances postischemic ventricular function and reduces infarct size. Endogenous adenosine also appears to modulate myocardial ischemic and reperfusion injury. This review will summarize the beneficial effects of adenosine in reversibly and irreversibly injured myocardium and address potential mechanisms of action.


Infarct Size Ischemic Precondition Cardioprotective Effect Myocardial Stunning Endogenous Adenosine 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Belardinelli L, Shryock JC, Song Y, Wang D, Srinivas M (1995) Ionic basis of the electrophysiological actions of adenosine on cardiomyocytes. FASEB Journal 9:359–365.PubMedGoogle Scholar
  2. 2.
    Lasley RD, Rhee JW, Van Wylen DGL, Mentzer RM (1990) Adenosine A1, receptor mediated protection of the globally ischemic isolated rat heart. J Mol Cell Cardiol 22:39–47.PubMedCrossRefGoogle Scholar
  3. 3.
    Lasley RD, Mentzer RM (jrJr) (1992) Adenosine improves the recovery of postischemic myocardial function via an adenosine A1, receptor mechanism. Am J Physiol 263:H1460–H1465.PubMedGoogle Scholar
  4. 4.
    Lasley RD, Konyn PJ, Hegge JO, Mentzer RM Jr (1995) The effects of ischemic and adenosine preconditioning on interstitial fluid adenosine and myocardial infarct size. Am J Physiol 269:H1460–H1466.PubMedGoogle Scholar
  5. 5.
    Mentzer RM Jr, Biinger R, Lasley RD (1993) Adenosine enhanced preservation of myocardial function and energetics. Possible involvement of the adenosine A., receptor system. Cardiovasc Res 27:28–35.CrossRefGoogle Scholar
  6. 6.
    Zhou Z, Bünger R, Lasley RD, Hegge JO, Mentzer RM Jr (1993) Adenosine pretreatment increases cytosolic phosphorylation potential and attenuates postischemic cardiac dysfunction in swine. Surg Forum 44:249–252.Google Scholar
  7. 7.
    Yao Z, Gross GJ (1993) Glibenclamide antagonizes adenosine Al receptor-mediated cardioprotection in stunned canine myocardium. Circulation 88:235–244.PubMedCrossRefGoogle Scholar
  8. 8.
    Graver GJ, Baird AJ, Sleph PG (1996). Lack of a pharmacologic interaction between ATP-sensitive potassium channels and adenosine A(l) receptors in ischemic rat hearts. Cardiovasc Res 31:511–517.Google Scholar
  9. 9.
    Lasley RD, Mentzer RM Jr (1993): Pertussis toxin blocks adenosine A1 receptor mediated protection of the ischemic rat heart. J Mol Cell Cardiol 25:815–821.PubMedCrossRefGoogle Scholar
  10. 10.
    Randhawa MPS Jr, Lasley RD, Mentzer RM Jr (1995): Salutary effects of exogenous adenosine on canine myocardial stunning in vivo. J Thorac Cardiovasc Surg 110:63–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Sekili S, Jeroudi MO, Tang XL, Zughaib M, Sun JZ, Bolli R (1995) Effect of adenosine on myocardial’ stunning’ in the dog. Circ Res 76:82–94.PubMedCrossRefGoogle Scholar
  12. 12.
    Van Wylen DGL, Willis J, Sodhi J, Weiss RJ, Lasley RD, Mentzer RM (1990) Cardiac microdialysis to estimate interstitial adenosine and coronary blood flow. Am J Physiol 258:H1642–H1649.Google Scholar
  13. 13.
    Yao Z, Gross GJ (1994) A comparison of adenosine-induced cardioprotection and ischemic preconditioning in dogs. Efficacy, time course, and role of KATP channels. Circulation 89:1229–1236.PubMedCrossRefGoogle Scholar
  14. 14.
    Liu GS, Thornton J, Van Winkle D, Stanley AWH, Olsson RA, Downey JM (1991) Protection against infarction afforded by preconditioning is mediated by A1, adenosine receptors in rabbit heart. Circulation 84:350–356.PubMedCrossRefGoogle Scholar
  15. 15.
    Lasley RD, Noble MA, Konyn PJ, Mentzer RM Jr (1995) Different effects of an adenosine A1, analogue and ischemic preconditioning in isolated rabbit hearts. Ann Thorac Surg 60:1698–1703.PubMedCrossRefGoogle Scholar
  16. 16.
    Homeister JW, Hoff PT, Fletcher DD, Lucchesi BR (1990): Combined adenosine and lidocaine administration limits myocardial reperfusion injury. Circulation 82:595–608.PubMedCrossRefGoogle Scholar
  17. 17.
    Dorheim TA, Hoffman A, Van Wylen DGL, Mentzer RM Jr (1991) Enhanced interstitial fluid adenosine attenuates myocardial stunning. Surgery 110: 136–145.PubMedGoogle Scholar
  18. 18.
    Hudspeth DA, Williams MW, Zhao ZQ, Sato H, Nakanishi K, McGee DS, Hammon JW Jr, Vinten-Johansen J, Van Wylen DGL (1994) Pentostatin-augmented interstitial adenosine prevents postcardioplegia injury in damaged hearts. Ann Thorac Surg 58:719–727.PubMedCrossRefGoogle Scholar
  19. 19.
    Kirkeboen KA, Ilebekk A, Tonnessen T, Leistad E, Naess PA, Christensen G, Aksnes G (1994) Cardiac contractile function following repetitive brief ischemia: effects of nucleoside transport inhibition. Am J Physiol 267:H57–H65.PubMedGoogle Scholar
  20. 20.
    Silva PH, Dillon D, Van Wylen DG (1995) Adenosine deaminase inhibition augments interstitial adenosine but does not attenuate myocardial infarction. Cardiovasc Res 29:616–623.PubMedGoogle Scholar
  21. 21.
    Martin BJ, Lasley RD, Mentzer RM Jr (1996): Infarct size reduction with the nucleoside transport inhibitor R75231 in swine. Am J Physiol In Press.Google Scholar
  22. 22.
    Zhao ZQ, McGee S, Nakanishi K, Toombs CF, Johnston WE, Ashar MS, Vinten-Johansen J (1993) Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit. Circulation 88:709–719.PubMedCrossRefGoogle Scholar
  23. 23.
    Hoshida S, Kuzuya T, Nishida M, Yamashita N, Oe H, Hori M, Kamada T, Tada M (1994) Adenosine blockade during reperfusion reverses the infarct limiting effect in preconditioned canine hearts. Cardiovasc Res 28:1083–1088.PubMedCrossRefGoogle Scholar
  24. 24.
    Cronstein BN, Levin RI, Belanoff J, Weissmann G, Hirschhorn R (1986) Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells. J Clin Invest 78:760–770.PubMedCrossRefGoogle Scholar
  25. 25.
    Murry CE, Jennings RB, Reimer KA (1986): Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136.PubMedCrossRefGoogle Scholar
  26. 26.
    Auchampach JA, Gross GJ (1993): Adenosine Al receptors, KATP channels, and ischemic preconditioning in dogs. Am J Physiol 264:H1327–H1336.PubMedGoogle Scholar
  27. 27.
    Lasley RD, Anderson GM, Mentzer RM Jr (1993): Ischemic and hypoxic preconditioning enhance postischemic recovery of function in the rat heart. Cardiovasc Res 27:565–570.PubMedCrossRefGoogle Scholar
  28. 28.
    Ganote CE, Armstrong S, Downey JM (1993) Adenosine and Al selective agonists offer minimal protection against ischaemic injury to isolated rat cardiomyocytes. Cardiovasc Res 27:1670–1676.PubMedCrossRefGoogle Scholar
  29. 29.
    Kirsch GE, Codina J, Birnbaumer L, Brown AM (1990) Coupling of ATP-sensitive K+ channels to Al receptors by G proteins in rat ventricular myocytes. Am J Physiol 259:H820–H826.PubMedGoogle Scholar
  30. 30.
    Ito H, Vereecke J, Carmeliet E (1994) Mode of regulation by G protein of the ATP-sensitive K+ channel in guinea-pig ventricular cell membrane. J Physiol 478:101–107.PubMedGoogle Scholar
  31. 31.
    Toombs CF, McGee DS, Johnston WE, Vinten-Johansen J (1993) Protection from ischaemic-reperfusion injury with adenosine pretreatment is reversed by inhibition of ATP sensitive potassium channels. Cardiovasc Res 27:623–629.PubMedCrossRefGoogle Scholar
  32. 32.
    Xu J, Wang L, Hurt CM, Pelleg A (1994): Endogenous adenosine does not activate ATP-sensitive potassium channels in the hypoxic guinea pig ventricle in vivo. Circulation 89:1209–1216.PubMedCrossRefGoogle Scholar
  33. 33.
    Miura T, Goto M, Miki T, Sakamoto J, Shimamoto K, Iimura O (1995) Glibenclamide, a blocker of ATP-sensitive potassium channels, abolishes infarct size limitation by preconditioning in rabbits anesthetized with xylazine/pentobarbital but not with pentobarbital alone. J Cardiovasc Pharmacol 25:531–538.PubMedCrossRefGoogle Scholar
  34. 34.
    Ytrehus K, Liu Y, Downey JM (1994): Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol 266:H1145–H1152.PubMedGoogle Scholar
  35. 35.
    Mitchell MB, Meng X, Ao L, Brown JM, Harken AH, Banerjee A (1995) Preconditioning of isolated rat heart is mediated by protein kinase C. Circ Res 76:73–81.PubMedCrossRefGoogle Scholar
  36. 36.
    Henry P, Demolombe S, Puceat M, Escande D (1996) Adenosine A(l) stimulation activates delta-protein kinase c in rat ventricular myocytes. Circ Res 78:161–165.PubMedCrossRefGoogle Scholar
  37. 37.
    Przyklenk K, Sussman MA, Simkhovich BZ, Kloner RA (1995) Does ischemic preconditioning trigger translocation of protein kinase C in the canine model? Circulation 92:1546–1557.PubMedCrossRefGoogle Scholar
  38. 38.
    Lasley RD, Anderson GM, Mentzer RM Jr (1994) Adenosine attenuates phorbol ester-induced negative inotropic and vasoconstrictive effects in rat hearts. Am J Physiol 266:H2159–H2166.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Robert D. Lasley

There are no affiliations available

Personalised recommendations