Cardiovascular Drugs and Therapy

, Volume 5, Issue 5, pp 933–938 | Cite as

Preconditioning myocardium with ischemia

  • Robert B. Jennings
  • Charles E. Murry
  • Keith A. Reimer
Focused Issue on Stunned Myocardium


Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stunning remains fully developed. Preconditioned, stunned, myocardium differs from control “virgin” myocardium in that adenine nucleotide content is reduced to about 50–70% of control, whereas creatine phosphate (CP) greatly exceeds normal-the so-called CP overshoot. When preconditioned myocardium is subjected to sustained ischemia, ATP utilization and anaerobic glycolysis occur at much slower rates than those observed in virgin myocardium. As a result of the early difference in metabolic rate, a longer period of ischemia is required for the ATP and lactate of the preconditioned tissue to reach the levels associated with irreversible injury. Associated with this change is a delay in myocyte death.

The molecular events responsible for slower ischemic metabolism and associated tolerance of preconditioned, stunned tissue to a new ischemic episode are not known. Among the reactions that could cause a reduction in energy metabolism is reduced ∼P expenditure by stunned myocardium attempting to contract during the initial phase of ischemia. However, results from in vivo and in vitro experiments suggest that although stunning may be necessary for preconditioning to develop, it alone is not sufficient to cause preconditioning. Alternatively, metabolic changes may be explained by depressed activity of the mitochondrial ATP ase during the epsiode of sustained ischemia. However, no direct experimental evidence supporting this hypothesis is available up to the present time.

Key Words

anaerobic glycolysis demand for ∼P ATP adenosine reversible injury irreversible injury 


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  1. 1.
    Jennings RB, Murry CE, Steenbergen CJr., Reimer KA. Development of cell injury in sustained acute ischemia. Circulation 1990;82 (Suppl):II2-II12.Google Scholar
  2. 2.
    Jennings RB, Schaper J, Hill ML, et al. Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure. Circ Res 1985;56:262–278.Google Scholar
  3. 3.
    Jennings RB, Murry CE, Reimer KA. Myocardial effects of brief periods of ischemia followed by reperfusion. In: Kellermann JJ, Braunwald E, eds. Advances in cardiology, Vol. 37. Basel: Karger, 1990:7–31.Google Scholar
  4. 4.
    Reimer KA, Murry CE, Jennings RB. Cardiac adaptation to ischemia: Ischemic preconditioning increases myocardial tolerance to subsequent ischemic episodes. Circulation 1990;82:2266–2268.Google Scholar
  5. 5.
    Reimer KA, Hill ML, Jennings RB. Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 1981; 13:229–239.Google Scholar
  6. 6.
    Bolli R. Mechanism of myocardial “stunning.’ Circulation 1990;82:723–738.Google Scholar
  7. 7.
    Knowlton AA, Brecher P, Ngou S, Apstein CS. Brief cardiac ischemia induces expression of heat shock protein (Abstr). Circulation 1989;80:II237.Google Scholar
  8. 8.
    Fleischmann KE, Brand T, Sharma HS, et al. Gene expression in a preconditioning model (Abstr). Circulation 1990;82 (Suppl):III464Google Scholar
  9. 9.
    Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay in lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–1136.Google Scholar
  10. 10.
    Murry CE, Richard VJ, Jennings RB, Reimer KA. Myocardial protection is lost before contractile function recovers from ischemic preconditioning. Am J Physiol (Heart Circ Physiol) 1991;260:H796-H804.Google Scholar
  11. 11.
    Basuk WL, Reimer KA, Jennings RB. Effect of repetitive brief episodes of ischemia on cell volume, electrolytes and ultrastructure. J Am Coll Cardiol 1986;8 (Suppl):33A-41A.Google Scholar
  12. 12.
    Hoffmeister HM, Mauser M, Schaper W. Repeated short periods of regional myocardial ischemia: Effect on local function and high energy phosphate levels. Basic Res Cardiol 1986;81:361–371.Google Scholar
  13. 13.
    Henrichs KJ, Matsuoka H, Schaper W. Influence of repetitive coronary occlusions on myocardial adenine nucleosides, high energy phosphates and ultrastructure. Basic Res Cardiol 1987;82:557–565.Google Scholar
  14. 14.
    Lange R, Ingwall JS, Hale SL, et al. Effects of recurrent ischemia on myocardial high energy phosphate content in canine heart. Basic Res Cardiol 1984;79:469–478.Google Scholar
  15. 15.
    Swain JL, Sabina RL, Hines JJ, et al. Repetitive episodes of brief ischemia (12 min) do not produce a cumulative depletion of high energy phosphate compounds. Cardiovasc Res 1984;18:264–269.Google Scholar
  16. 16.
    Li GC, Vasquez JA, Gallagher KP, Lucchesi BR. Myocardial protection with preconditioning. Circulation 1990;82: 609–619.Google Scholar
  17. 17.
    Schott RJ, Rohmann S, Braun ER, Schaper W. Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 1990;66:1133–1142.Google Scholar
  18. 18.
    Downey JM, Jordan M. Preconditioning limits infarct size in rabbits. Circulation 1989;80 (Suppl):II238.Google Scholar
  19. 19.
    Reimer KA, Murry CE, Yamasawa I, et al. Four brief periods of myocardial ischemia cause no cumulative ATP loss or necrosis. Am J Physiol 1986;251:H1306-H1315.Google Scholar
  20. 20.
    Jennings RB, Reimer KA, Steenbergen CJr. Myocardial ischemia revisited. The osmolar load, membrane damage, and reperfusion (editorial). J Mol Cell Cardiol 1986;18: 769–780.Google Scholar
  21. 21.
    Jennings RB, Reimer KA, Steenbergen CJr, Murry CE. Energy metabolism in myocardial ischemia. In: Dhalla NS, Innes IR, Beamish RE, eds. Myocardial ischemia. Boston: Martinus Nijhoff Publishers, 1987:185–198.Google Scholar
  22. 22.
    Nao BS, McClanahan TB, Groh MA, et al. The time limit of effective ischemic preconditioning in dogs (Abstr). Circulation 1990;82 (Suppl):III271.Google Scholar
  23. 23.
    Downey JM, Thornton JD, Liu GS, Stanley AWH. Preconditioning does not involve the synthesis of a protective protein. Circulation 1990;82:III271.Google Scholar
  24. 24.
    Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during sustained ischemia. Circ Res 1990;66:913–931.Google Scholar
  25. 25.
    Jennings RB, Reimer KA. Lethal myocardial ischemic injury. Am J Pathol 1981;102:241–255.Google Scholar
  26. 26.
    Rouslin W, Ericsson JLE, Solaro RJ. Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle. Am J Physiol 1986;250:H503-H508.Google Scholar
  27. 27.
    Jones RN, Reimer KA, Hill ML, Jennings RB. Effect of hypothermia on changes in high energy phosphate production and utilization in total ischemia. J Mol Cell Cardiol 1982;14 (Suppl):123–130.Google Scholar
  28. 28.
    Rouslin W. The mitochondrial adenosine 5′-triphosphatase in slow and fast heart rate hearts. Am J Physiol 1987; 252:H622-H627.Google Scholar
  29. 29.
    Thornton JD, Van Winkle DM, Downey JM. Preconditioning protection is mediated through adenosine receptors (Abstr). Circulation 1990;82 (Suppl):III464.Google Scholar
  30. 30.
    Schott R, Nao B, Strieter M, et al. Heat shock does not “precondition” canine myocardium (Abstr). Circulation 1990;82:III464.Google Scholar
  31. 31.
    Jennings RB, Murry CE, Reimer KA. Energy metabolism in preconditioned and control myocardium: Effect of total ischemia. J Mol Cell Cardiol 1990, in press.Google Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Robert B. Jennings
    • 1
  • Charles E. Murry
    • 2
  • Keith A. Reimer
    • 1
  1. 1.Department of PathologyDuke University Medical CenterDurhamUSA
  2. 2.Department of PathologyUniversity of Washington School of MedicineSeattleUSA

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