Skip to main content
SpringerLink
Log in

Role of Adenosine in the Treatment of Myocardial Stunning

  • Chapter
Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion

Summary

Adenosine is an endogenous nucleoside produced from the breakdown of adenosine triphosphate (ATP) that possesses a number of complex cellular and metabolic effects that could ameliorate postischemic contractile dysfunction (myocardial stunning). Potential mechanisms include the repletion of high-energy phosphate stores, reduced myocardial oxygen consumption, a decrease in oxygen-derived free radicals, restoration of calcium homeostasis, and an increase in regional myocardial blood flow. Experimental studies have shown that adenosine can reduce myocardial stunning with or without a concomitant increase in the total myocardial ATP stores. Adenosine may be a useful pharmacologic strategy in the prevention and treatment of ventricular dysfunction following episodes of regional or global ischemia, although further studies are needed to clarify the precise cellular mechanisms involved.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol 1988; 12: 239–249.

    Article  PubMed  CAS  Google Scholar 

  2. Braunwald E, Kloner RA. Myocardial reperfusion: A double-edged sword. J Clin Invest 1985; 76: 1713–1719.

    Article  PubMed  CAS  Google Scholar 

  3. Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 1975; 56: 978–985.

    Article  PubMed  CAS  Google Scholar 

  4. Lavalle M, Cox D, Patrick TA, Vatner SF. Salvage of myocardial function by coronary artery reperfusion 1, 2 and 3 hours after occlusion in conscious dogs. Circ Res 1983; 53: 235–247.

    Google Scholar 

  5. Bush LR, Buja LM, Samowitz W. Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs. Circ Res 1983; 53: 248–263.

    PubMed  CAS  Google Scholar 

  6. Matsuzaki M, Gallagher KP, Kemper WS, White F, Ross J Jr. Sustained regional dysfunction produced by prolonged coronary stenosis: Gradual recovery after reperfusion. Circulation 1983; 68: 170–182.

    Article  PubMed  CAS  Google Scholar 

  7. Wijns W, Serruys PW, Slager CJ, et al. Effect of coronary occlusion during percutaneous transluminal angioplasty in humans on left ventricular chamber stiffness and regional diastolic pressure-radius relation. J Am Coll Cardiol 1986; 7: 455–463.

    Article  PubMed  CAS  Google Scholar 

  8. Ledingham S, Katayama O, Lachno D, Patel N. Yacoub M. Beneficial effect of adenosine during reperfusion following prolonged cardioplegic arrest. Cardiovasc Res 1990; 24: 247–253.

    Article  PubMed  CAS  Google Scholar 

  9. Owen P, Dennis S, Opie LH. Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. Circ Res 1990; 66: 344–354.

    PubMed  CAS  Google Scholar 

  10. Reimer KA, Jennings RB. Myocardial ischemia, hypoxia and infarction. In: Fozzard HA, ed. The heart and cardiovascular system. New York: Raven Press, 1986: 1133–1201.

    Google Scholar 

  11. Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and energy balance of the heart. Ann Rev Physiol 1974; 36: 413–459.

    Article  CAS  Google Scholar 

  12. Opie LH. Myocardial ischemia-Metabolic pathways and implications of increased glycolysis. Cardiovasc Drugs Ther 1990; 4: 777–790.

    Article  PubMed  Google Scholar 

  13. Jennings RB, Reimer KA, Hill ML, Mayer SE. Total ischemia in dog hearts, in vitro: 1. Comparison of high energy phosphate production, utilization, and depletion, and of adenine nucleotide catabolism in total ischemia in vitro vs. severe ischemia in vivo. Circ Res 1981; 49: 892–900.

    PubMed  CAS  Google Scholar 

  14. Reimer KA, Jennings RB, Hill ML. Total ischemia in dog hearts, in vitro. 2. High energy phosphate depletion and associated defects in energy metabolism, cell volume regulation and sarcolemmal integrity. Circ Res 1981; 49: 901–911.

    PubMed  CAS  Google Scholar 

  15. Schrader J. Metabolism of adenosine and sites of production in the heart. In: Berne RM, Rall TW, Rubio R, eds. Regulatory function of adenosine. The Hague: Martinus/Nijhoff Publishers, 1983: 133–156.

    Google Scholar 

  16. Clanachan AS, Heaton TP, Parkinson FE. Drug interactions with nucleoside transport systems. In: Gerlach E, Becker BF, eds. Topics and perspectives in adenosine research. Berlin: Springer-Verlag, 1987: 118–130.

    Google Scholar 

  17. McCord JM. Oxygen-derived free radicals in postischemic tissue. N Engl J Med 1985; 312: 159–163.

    Article  PubMed  CAS  Google Scholar 

  18. Pasque MK, Spray TL, Pellom GL, et al. Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart. J Thorac Cardiovasc Surg 1982; 83: 390–398.

    PubMed  CAS  Google Scholar 

  19. DeBoer LWV, Ingwall JS, Kloner RA, Braunwald E. Prolonged derangements of canine myocardial purine metabolism after a brief coronary occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci USA 1980; 77: 5471–5475.

    Article  PubMed  CAS  Google Scholar 

  20. Ramkumar V, Pierson G, Stiles GL. Adenosine receptors: Clinical implications and biochemical mechanisms. Progr Drug Res 1988; 32: 196–245.

    Google Scholar 

  21. Segal M. Intracellular analysis of a postsynaptic action of adenosine in the rat hyppocampus. Eur J Pharmacol 1982; 79: 193–199.

    Article  PubMed  CAS  Google Scholar 

  22. Swain JL, Hines JJ, Sabina RL, Holmes FW. Accelerated repletion of ATP and GTP pools in postischemic canine myocardium using a precursor of purine de novo synthesis. Circ Res 1982; 51: 102–105.

    PubMed  CAS  Google Scholar 

  23. Carlsson L, Abrahamsson T, Almgren O. Local release of noradrenaline during acute ischemia. An experimental study in the isolated perfused rat heart. J Cardiovasc Pharmacol 1985; 7: 791–798.

    Article  PubMed  CAS  Google Scholar 

  24. Richardt G, Waas W, Kranzhomig R, Mayer E, Schomig A. Adenosine inhibits exocytotic release of endogenous noradrenalin in rat heart: A protective mechanism in early myocardial ischemia. Circ Res 1987; 61: 117–123.

    PubMed  CAS  Google Scholar 

  25. Belardinelli L, West A, Crampton R, Berne RM. Chronotropic and dromotropic effects of adenosine. In: Berne RM, Rall TW, Rubio R, eds. Regulatory function of adenosine. Boston: Martinus/Nijoff, 1983: 377–396.

    Google Scholar 

  26. Mainwaring R, Lasley R, Rubio R, Wyatt DA, Mentzer RM. Adenosine stimulates glucose uptake in the isolated rat heart. Surgery 1988; 103: 445–449.

    PubMed  CAS  Google Scholar 

  27. Wyatt DA, Edmunds MC, Rubio R, Berne RM, Lasley RD, Mentzer RM Jr. Adenosine stimulates glycolytic flux in isolated perfused rat hearts by AI-adenosine receptors. Am J Physiol 1989; 257: H1952 - H1957.

    PubMed  CAS  Google Scholar 

  28. Fredholm BB. Methods used to study the involvement of adenosine in the regulation of lipolysis. In: Paton DM, ed. Methods in pharmacology. New York: Plenum Press, 1985: 337–357.

    Google Scholar 

  29. Forman MB, Virmani R. Pathogenesis and modification of myocardial reperfusion injury. In: Gersh BJ, Rahimtoola SH, eds. Acute myocardial infarction. New York: Elsevier Science Publishing, 1991: 349–370.

    Google Scholar 

  30. Burton KP. Superoxide dismutase enhances recovery following myocardial ischemia. Am J Physiol 1985; 248: H637 - H643.

    PubMed  CAS  Google Scholar 

  31. Przyklenk K, Whittaker P, Kloner RA. Direct evidence that oxygen free radicals cause contractile dysfunction in vivo (Abstr). Circulation 1988; 78 (Suppl II): 264.

    Google Scholar 

  32. Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res 1989; 65: 607–622.

    PubMed  CAS  Google Scholar 

  33. Zweier JL, Flaherty JT, Weisfeldt ML. Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci USA 1987; 84: 1404–1407.

    Article  PubMed  CAS  Google Scholar 

  34. Tribble DL, Aw TY, Jones DP. The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology 1987; 7: 377–386.

    Article  PubMed  CAS  Google Scholar 

  35. Engler R. Granulocytes and oxidative injury in myocardial ischemia and reperfusion. Fed Proc 1987; 46: 2395–2396.

    Google Scholar 

  36. Cronstein BN, Kramer SB, Weissmann G, Hirschhorn R. Adenosine: A physiologic modulator of superoxide anion generation by human neutrophils. J Exp Med 1983; 158: 1160–1177.

    Article  PubMed  CAS  Google Scholar 

  37. Tanabe M, Terashita Z, Nishikawa K, Hirata M. Inhibition of coronary circulatory failure and thromboxane A2 release during coronary occlusion and reperfusion. J Cardiovasc Pharmacol 1984; 6: 442–448.

    Article  PubMed  CAS  Google Scholar 

  38. Steenbergen C, Murphy E, Levy L, London RE. Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res 1987; 60: 700–707.

    PubMed  CAS  Google Scholar 

  39. Marban E, Kitakze M, Kusuoka H, Porterfield JK, Yuo DT, Chacko VP. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci USA 1987; 86: 6005–6009.

    Article  Google Scholar 

  40. Krause SM, Jacobus WE, Becker LC. Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic “stunned” myocardium. Circ Res 1989; 65: 526–530.

    PubMed  CAS  Google Scholar 

  41. Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E. Pathophysiology and pathogenesis of stunned myocardium: Depressed Ca2+activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 1987; 79: 950–961.

    Article  PubMed  CAS  Google Scholar 

  42. Przyklenk K, Ghafari GB, Eitzman DT, Kloner RA. Nifedipine administered post reperfusion ablates systolic contractile dysfunction of the postischemic “stunned” myocardium. J Am Coll Cardiol 1989; 13: 1176–1183.

    Article  PubMed  CAS  Google Scholar 

  43. Kuroda Y. Modulation of calcium channels through different adenosine receptors; ADO-1 and ADO-2. In: Stafanovich V, Rudolphi K, Schubert P, eds. Adenosine: receptors and modulation of cell function. Oxford, England: IRL Press Limited, 1985: 233–239.

    Google Scholar 

  44. Schubert P. Synaptic and non-synaptic modulation by adenosine: A differential action of K- and Ca-fluxes. In: Stafanovich V, Rudolphi K, Schubert P, eds. Adenosine: Receptor and modulation of cell function. Oxford, England: IRL Press Limited, 1985: 117–129.

    Google Scholar 

  45. Bolli R, Triana JF, Jeroudi MO. Prolonged impairment of coronary vasodilation after reversible ischemia: Evidence for microvascular “stunning”. Circ Res 1990; 67: 332–343.

    PubMed  CAS  Google Scholar 

  46. Dauber IM, VanBenthuysen KM, McMurtry IF, et al. Functional coronary microvascular injury evident as increased permeability due to brief ischemia and reperfusion. Circ Res 1990; 66: 986–998.

    PubMed  CAS  Google Scholar 

  47. Stahl LD, Aversano TR, Becker LC. Selective enhancement of function of stunned myocardium by increased flow. Circulation 1986; 74: 843–851.

    Article  PubMed  CAS  Google Scholar 

  48. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74 (5): 1124–1136.

    Article  PubMed  CAS  Google Scholar 

  49. Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultra-structural damage during a sustained ischemic episode. Circ Res 1990; 66: 913–931.

    PubMed  CAS  Google Scholar 

  50. 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: 816–824.

    PubMed  CAS  Google Scholar 

  51. Liu GS, Thornton J, Van Winkle DM, Stanley AWH, Olsson RA, Downey JM. Protection against infarction afforded by preconditioning is mediated by Al adenosine receptors in the rabbit heart. Circulation 1991; 84: 350–356.

    PubMed  CAS  Google Scholar 

  52. Pitarys CJ II, Virmani R, Vildibill HD Jr., Jackson EK, Forman MB. Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 1991; 83: 237–247.

    PubMed  Google Scholar 

  53. Reibel DK, Rovetto MJ. Myocardial adenosine salvage rates and restoration of ATP content following ischemia. Am J Physiol 1979; 237 (2): H247 - H252.

    PubMed  CAS  Google Scholar 

  54. Foker JE, Einzig S, Wang T. Adenosine metabolism and myocardial preservation: Consequences of adenosine catabolism on myocardial high-energy compounds and tissue blood flow. J Thorac Cardiovasc Surg 1980; 80: 506–516.

    PubMed  CAS  Google Scholar 

  55. Bolling SF, Bies LE, Bove HL, Gallagher KP. Augmenting intracellular adenosine improves myocardial recovery. J Thorac Cardiovasc Surg 1990; 99: 469–474.

    PubMed  CAS  Google Scholar 

  56. DeWitt DF, Jochim KE, Behrendt DM. Nucleotide degradation and functional impairment during cardioplegia: Amelioration by inosine. Circulation 1983; 67 (1): 171–178.

    Article  PubMed  CAS  Google Scholar 

  57. Henrichs KJ, Matsuoka H, Schaper W. Enhanced postischemic ATP repletion by pharmacological inhibition of nucleoside washout and catabolism. J Cardiovasc Pharmacol 1988; 11: 694–700.

    Article  PubMed  CAS  Google Scholar 

  58. Zimmer HG. Normalization of depressed heart function in rats by ribose. Science 1983; 23: 81–82.

    Article  Google Scholar 

  59. Mauser M, Hoffmeister HM, Nienaber C, Schaper W. Influence of ribose, adenosine, and “AICAR” on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog. Cire Res 1985; 56: 220–230.

    CAS  Google Scholar 

  60. Abd-Elfattah AS, Jessen ME, Lekven J, Doherty NE,III, Brunsting LA, Wechsler AS. Myocardial reperfusion injury: Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury. Circulation 1988;78 (Suppl III):III224—III235.

    Google Scholar 

  61. Arnold JMO, Braunwald E, Sandor T, Kloner RA. Inotropic stimulations of reperfused myocardium: Effects on infarct size and myocardial function. J Am Coll Cardiol 1985; 6: 1026–1034.

    Article  PubMed  CAS  Google Scholar 

  62. Becker LC, Levine JH, DiPaula AF, Guarnieri T, Aversano T. Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation. J Am Coll Cardiol 1986; 7: 580–589.

    Article  PubMed  CAS  Google Scholar 

  63. Przyklenk K, Kloner RA. Superoxide dismutase plus catalase improve contractile function in the canine model of the “stunned myocardium”. Cire Res 1986; 58: 148–156.

    CAS  Google Scholar 

  64. Asimakis GK, Sandhu GS, Conti VR, Sordahl LA, Zwischenberger JB. Intermittent ischemia produces a cumulative depletion of mitochondrial adenine nucleotides in the isolated perfused rat heart. Circ Res 1990; 66: 302–310.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Mervyn B. Forman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos E. Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Cape Town, Cape Town, South Africa

    Lionel H. Opie MD, DPhil. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

  2. Division of Cardiology, Stanford University Medical Center, Stanford, California, USA

    Lionel H. Opie MD, DPhil. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Kluwer Academic Publishers

About this chapter

Cite this chapter

Forman, M.B., Velasco, C.E. (1992). Role of Adenosine in the Treatment of Myocardial Stunning. In: Opie, L.H. (eds) Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1517-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-1517-9_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-7923-1793-7

  • Online ISBN: 978-1-4613-1517-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation