Adenosine and Adenosine Receptor Protection of the Ischemic Heart

  • Robert D. Lasley
  • Robert J. MentzerJr.
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 181)


The purine nucleoside adenosine modulates the myocardial response to an imbalance in oxygen supply and demand by inducing coronary vasodilatation, negative dromotropy and chronotropy, and anti-adrenergic effects (1). Substantial evidence also exists that endogenous and exogenous adenosine modulate the heart’s response to the most severe form of oxygen supply/demand imbalance, i.e. myocardial ischemia. This review will summarize the results of work performed in our laboratory on the effects of adenosine in the ischemic and postischemic heart.


Leave Anterior Descend Myocardial Glucose Uptake Myocardial Glucose Utilization systOliC Wall Thicken Exogenous Adenosine 
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  1. 1.
    Belardinelli L, Linden J, Berne RM. The cardiac actions of adenosine. Prog Cardiovasc Dis 1989;32:73–97.PubMedCrossRefGoogle Scholar
  2. 2.
    Benson ES, Evans GT, Hallaway BE, Phibbs C, Freier EF. Myocardial creatine phosphate and nucleotides in anoxie cardiac arrest and recovery. Am J Physiol 1961;201:687–93.Google Scholar
  3. 3.
    Namm DH. Myocardial nucleotide synthesis from purine bases and nucleosides. Comparison of the rates of formation of purine nucleotides from various precursors and identification of the enzymatic routes for nucleotide formation in the isolated rat heart. Circ Res 1973;33:686–965.PubMedGoogle Scholar
  4. 4.
    Liu MS, Feinberg H. Incorporation of adenosine-8-14C and inosine-8-14C into rabbit heart adenine nucleotides. Am J Physiol 1971;220:1242–84.PubMedGoogle Scholar
  5. 5.
    Ely SW, Mentzer RM, Jr, Lasley RD, Lee BK, Berne RM. Functional and metabolic evidence of enhanced tolerance to ischemia and reperfusion with adenosine. J Thorac Cardiovasc Surg 1985;90:549–56.PubMedGoogle Scholar
  6. 6.
    Wyatt DA, Ely SW, Lasley RD, Walsh R, Mainwaring R, Berne RM, Mentzer RM, Jr. Purine-enriched asanguineous cardioplegia retards adenosine triphosphate degradation during ischemia and improves postischemic ventricular function. J Thorac Cardiovasc Surg 1989;97:771–78.PubMedGoogle Scholar
  7. 7.
    Reibel DK, Rovetto MJ. Myocardial adenosine salvage rates and restoration of ATP content following ischemia. Am J Physiol 1979;237 (Heart Circ. Physiol 6):H247–H52.PubMedGoogle Scholar
  8. 8.
    Ambrosio G, Jacobus WE, Mitchell MC, Litt MR, Becker LC. Effects of ATP precursors on ATP and free ADP content and functional recovery of postishemic hearts. Am J Physiol 1989;256 (Heart Circ. Physiol. 25):H560–H66.PubMedGoogle Scholar
  9. 9.
    Neely JR, Grotyohann LW. Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 1984;55:816–24.PubMedGoogle Scholar
  10. 10.
    Mallet RT, BHnger R. Metabolic protection of post-ischemic phosphorylation potential and ventricular performance. In: Sideman S, Beyar R, editors. Interactive Phenomena in the Cardiac System, New York, Plenum Press, 1993;233–241.CrossRefGoogle Scholar
  11. 11.
    Lasley RD, Rhee JW, Van Wylen DGL, Mentzer RM. Adenosine A1 receptor mediated protection of the globally ischemic isolated rat heart. J Mol Cell Cardiol 1990;22:39–47.PubMedCrossRefGoogle Scholar
  12. 12.
    Lasley RD, Mentzer RM, Jr. Adenosine improves the recovery of postishemic myocardial function via an adenosine A1 receptor mechanism. Am J Physiol 1992;263:H1460–H65.PubMedGoogle Scholar
  13. 13.
    Lasley RD, Mentzer RM, Jr. Pertussis toxin blocks adenosine A1 receptor mediated protection of the ischemic rat heart. J Mol Cell Cardiol 1993;25:815–21.PubMedCrossRefGoogle Scholar
  14. 14.
    Nees S, Herzog V, Becker BF, Beck M, Des Rosiers C, Gerlach E. The coronary endothelium: a highly active metabolic barrier for adenosine. Basic Res Cardiol 1985;80:515–29.PubMedCrossRefGoogle Scholar
  15. 15.
    Van Wylen DGL, Willis J, Sodhi J, Weiss RJ, Lasley RD, Mentzer RM. Cardiac microdialysis to estimate interstitial adenosine and coronary blood flow. Am J Physiol 1990;258:H1642–H49.PubMedGoogle Scholar
  16. 16.
    Dorheim TA, Wang T, Mentzer RM, Jr, Van Wylen DG. Interstitial purine metabolites during regional myocardial ischemia. J Surg Res 1990;48:491–97.PubMedCrossRefGoogle Scholar
  17. 17.
    Dorheim TA, Hoffman A, Van Wylen DGL, Mentzer RM, Jr. Enhanced interstitial fluid adenosine attenuates myocardial stunning. J Surg 1991;110:136–45.Google Scholar
  18. 18.
    Randhawa MPS, Jr, Lasley RD, Anderson G, Hegge J, Mentzer RM, Jr. Effects of adenosine on flow, function, and interstitial nucleoside levels in normal and stunned myocardium. Surg Forum 1992;43:200–203.Google Scholar
  19. 19.
    Mainwaring RD, Lasley R, Rubio R, Wyatt D, Mentzer R, Jr. Adenosine stimulates glucose uptake in the isolated rat heart. Surgery 1988;103:445–49.PubMedGoogle Scholar
  20. 20.
    Mentzer RM, Jr, BHnger R, Lasley RD. Adenosine enhanced preservation of myocardial function and energetics. Possible involvement of the adenosine A1 receptor system. Cardiovasc Res 1993;27:28–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Angello DA, Coddington NM, Berne RM. Adenosine and insulin mediate glucose uptake in normoxic rat hearts by different mechanisms. Am J Physiol 1993;265:H880–H85.PubMedGoogle Scholar
  22. 22.
    Wyatt DA, Edmunds MC, Rubio R, Berne RM, Lasley RD, Mentzer RM. Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors. Am J Physiol 1989;257 (Heart Circ. Physiol. 26):H1952–H57.PubMedGoogle Scholar
  23. 23.
    Jesmok GJ, Gross GJ, Hardman HF. The effect of adenosine on myocardial metabolism and oxygen consumption in the isolated dog heart preparation. J Mol Cell Cardiol 1978;10:249–61.PubMedCrossRefGoogle Scholar
  24. 24.
    Law WR, Raymond RM. Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo. Am J Physiol 254(Heart Circ Physiol 1988;23):H970–H75.Google Scholar
  25. 25.
    Dale WE, Hale CC, Kim HD, Rovetto MJ. Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. Circ Res 1991;69:791–99.PubMedGoogle Scholar
  26. 26.
    Buxton DB, Kjaer-Pederson K, Nguyen A. Metabolic effects of adenosine in the isolated perfused rat heart. J Mol Cell Cardiol 1992;24:173–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Lasley RD, Mentzer RM, Jr. Adenosine increases lactate release and delays the onset of contracture during global low flow ischemia. Cardiovasc Res 1993;27:96–101.PubMedCrossRefGoogle Scholar
  28. 28.
    Bünger R, Schulze K, Mentzer RM, Jr, Lasley RD. Adenosine improves cellular H handling during low-flow ischemia in perfused guinea pig heart. Drug Dev Res 1994;31:254.Google Scholar
  29. 29.
    Fralix TA, Murphy E, London RE, Steenbergen C. Protective effects of adenosine in the perfused rat heart: changes in metabolism and intracellular ion homeostasis. Am J Physiol 1993;264:C986–C94.PubMedGoogle Scholar
  30. 30.
    Zhou Z, BHnger R, Lasley RD, Hegge JH, Mentzer RM, Jr. Adenosine pretreatment increases cytosolic phosphorylation potential and attenuates postischemic cardiac dysfunction in swine. Surg Forum 1993;44:249–52.Google Scholar
  31. 31.
    Schwartz GG, Schaefer S, Meyerhoff DJ, Gober J, Fochler P, Massie B, Weiner MW. Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig. Circ Res 1990;67:490–500.PubMedGoogle Scholar
  32. 32.
    Dobson JG, Fenton RA, Romano FD. The antiadrenergic actions of adenosine in the heart. In: Gerlach E, Becker BF, editors. Topics and Perspectives in Adenosine Research. Berlin, Heidelberg, Springer-Verlag, 1987;356–368.Google Scholar
  33. 33.
    Lasley RD, Noble MA, Paulsen KL, Mentzer RM, Jr. Adenosine attenuates phorbol ester-induced negative inotropic and vasoconstrictive effects in the isolated rat heart. Am J Physiol 1994;266:H2159–H66.PubMedGoogle Scholar
  34. 34.
    Cushing DJ, Makujina SR, Sabouni MH, Mustafa SJ. Protein kinase C and phospholi-pase C in adenosine receptor-mediated relaxation in coronary artery. Am J Physiol 261 (Heart Circ Physiol 1991;30):H1848–H54.Google Scholar
  35. 35.
    Adkins WK, Barnard JW, Moore TM, Allison RC, Prasad VR, Taylor AE. Adenosine prevents PMA-induced lung injury via an A2 receptor mechanism. J Appl Physiol 1993;74:982–88.PubMedGoogle Scholar
  36. 36.
    Gwathmey JK, Hajjar RJ. Effect of protein kinase C activation on sarcoplasmic reticulum function and apparent myofibrillar Ca2+ sensitivity in intact and skinned muscles from normal and diseased human myocardium. Circ Res 1990;67:744–52.PubMedGoogle Scholar
  37. 37.
    Strasser RH, Braun-Dullaeus R, Walendzik H, Marquetant R. µ 1 -receptor- independent activation of protein kinase C in acute myocardial ischemia. Mechanisms for sensitization of the adenylyl cyclase system. Circ Res 1992;70:1304–12.PubMedGoogle Scholar
  38. 38.
    Lasley RD, Mentzer RM, Jr. The role of adenosine in extended myocardial preservation with the University of Wisconsin solution. J Thorac Cardiovasc Surg 1994;107:1356–63.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Robert D. Lasley
    • 1
  • Robert J. MentzerJr.
    • 1
  1. 1.Department of Surgery, Division of Cardiothoracic SurgeryUniversity of WisconsinMadisonUSA

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