The Cellular Basis of Stunned Myocardium

  • Hideo Kusuoka
  • Eduardo Marban
  • Myron L. Weisfeldt


Contractility is decreased after ischemia, even when there is no histologic evidence of irreversible injury; myocardium so afflicted has come to be known as ‘stunned.’ The contractility lesion in stunned myocardium might affect at least one of three major factors in force generation; the [Ca2+] transient, myofilament Ca2+-sensitivity and maximal Ca2+-activated force. Our results indicate that contractile dysfunction in stunned myocardium is characterized by a decline in maximal force and a shift to higher Ca in the myocardial sensitivity to extracellular Ca. The latter may reflect either a decrease in myofilament Ca2+-sensitivity or a decrease in the [Ca2+] transient. Reperfusion with a solution of low Ca concentration or an acidic solution ameliorated functional recovery, indicating that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning. Recent research suggests that the lower intramyocardial level at ATP may be an epiphenomenon and not a causal factor in stunning. Thus, we favor the hypothesis that calcium is the crucial mediator of reversible post-ischemic dysfunction.


Contractile Dysfunction Stun Myocardium Contractile Reserve Develop Pressure Reperfused Ischemic Heart 
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.
    Weiner JM, Apstein CS, Arthur JH, Pirzada FA, Hood Jr WB (1976) Persistence of myocardial injury following brief periods of coronary occlusion. Cardiovasc Res 10 678–686PubMedCrossRefGoogle Scholar
  2. 2.
    Braunwald E, Kloner RA (1982) The stunned myocardium: prolonged postischemic ventricular dysfunction. Circulation 60: 1146–1149CrossRefGoogle Scholar
  3. 3.
    Satler LF, Kent KM, Fox LM, Goldstein HA, Green CE, Rogers WJ, Pollas RS, Del Negro AA, Pearle DL, Rackley CE (1986) The assessment of contractile reserve after thrombolytic therapy for acute myocardial infarction. Am Heart J 111: 821–825PubMedCrossRefGoogle Scholar
  4. 4.
    Braunwald E, Kloner RA (1985) Myocardial reperfusion: a double-edged sword? J Clin Invest 76: 1713–1719PubMedCrossRefGoogle Scholar
  5. 5.
    Becker LC, Levine JH, DiPaula AF, Guarnieri T, Aversano T (1986) Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation. J Am Coll Cardiol 7: 580–589PubMedCrossRefGoogle Scholar
  6. 6.
    Neely JR, Grotyohann LW (1984) Role of glycloytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 55: 816–824PubMedGoogle Scholar
  7. 7.
    Shine KL, Douglas AM (1983) Low calcium reperfusion of ischemic myocardium. J Mol Cell Cardiol 15: 251–260PubMedCrossRefGoogle Scholar
  8. 8.
    Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E (1987) 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 79: 950–961PubMedCrossRefGoogle Scholar
  9. 9.
    Kitakaze M, Weisman HF, Marban E (1988) Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts. Circulation 77: 685–695PubMedCrossRefGoogle Scholar
  10. 10.
    Kitakaze M, Weisfeldt ML, Marban E (1988) Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 82: 920–927PubMedCrossRefGoogle Scholar
  11. 11.
    Kusuoka H, Weisfeldt ML, Zweier JL, Jacobus WE, Marba E (1986) Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate. Circ Res 59: 270–282PubMedGoogle Scholar
  12. 12.
    Marban E, Kusuoka H, Yue DT, Weisfeldt ML, Wier WG (1986) Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart. Mechanism and characteristics of steady contractile activation in intact myocardium. Circ Res 59: 262–269PubMedGoogle Scholar
  13. 13.
    Grinwald PM (1982) Calcium uptake during post-ischemic reperfusion in the isolated rat heart: influence of extracellular sodium. J Mol Cell Cardiol 14: 359–365PubMedCrossRefGoogle Scholar
  14. 14.
    Renlund DG, Gerstenblith G, Lakatta EG, Jacobus WE, Kallman CH, Weisfeldt ML (1984) Perfusate sodium during ischemia modifies post-ischemic functional and metabolic recovery in the rabbit heart. J Mol Cell Cardiol 16: 795–801PubMedCrossRefGoogle Scholar
  15. 15.
    Kitakaze M, Pike MM, Chacko VP, Marban E (1987) Direct measurement of cystolic free calcium during ischemia and reperfusion in ferret hearts, (abstract) Circulation 76: 380Google Scholar
  16. 16.
    Kloner RA, Deboer LWV, Darsee JR, Ingwall JS, Hale S, Tumas J, Braunwald E (1981) Prolonged abnormalities of myocardium salvaged by reperfusion. Am J Physiol 241: H591–H599PubMedGoogle Scholar
  17. 17.
    Mauser M, Hoffmeister HM, Nienaber C, Schaper W (1985) Influence of ribose, adenosine, and AICAR on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog. Circ Res 56: 220–230PubMedGoogle Scholar
  18. 18.
    Stahl L, Weiss HR, Becker LC (1988) Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 77:865–872PubMedCrossRefGoogle Scholar
  19. 19.
    Kusuoka H, Inoue M, Marban E (1988) Decreased efficiency of energy utilization in stunned myocardium, (abstract) Circulation 78: 11–261Google Scholar
  20. 20.
    Zweier JL, Flaherty JT, Weisfeldt ML (1987) Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci USA 84: 1404–1407PubMedCrossRefGoogle Scholar
  21. 21.
    Przyklenk K, Koner RA (1986) Superoxide dismutase plus catalase improve contractile function in the canine model of the ‘stunned myocardium’. Circ Res 58: 148–156PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1989

Authors and Affiliations

  • Hideo Kusuoka
    • 1
  • Eduardo Marban
    • 2
  • Myron L. Weisfeldt
    • 2
  1. 1.The First Department of MedicineOsaka University School of MedicineOsakaJapan
  2. 2.Division of Cardiology, Department of MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations