Advertisement

Molecular Mechanisms in “Stunned” Myocardium

  • Wolfgang Schaper

Summary

In a recent overview on stunning, Bolli [1] listed the three pillars on which theories on stunning rest: its causation by oxygen radicals, the amplification of damage by Ca2+ overload, and the resulting excitation contraction uncoupling. Our own experiments with SOD and catalase do not convince us that stunning is caused by free radicals, because we and others were unable to show improvement. An important pathway of radical generation, i.e., xanthine oxidase, does not exist in the hearts of several families of mammals, but stunning can of course be produced in these species. We agree with Bolli that stunning represents a disturbance of electromechanical coupling, but we acknowledge the controversy that exists with regard to the subcellular seat of the defect. Our results would support hypotheses that pinpoint the defect to the sarcoplasmic reticulum. However, the possibility of multiple defects should also be considered: Our finding of altered Ca2+ ATPase expression and Kusuoka’s finding of altered myofibrillar Ca2+ sensitivity are not necessarily mutually exclusive but may be complementary, or may represent different stages of ischemic damage. Our finding of decreased myosin expression may help to explain the long persistence of the contractile defect. From the available evidence, the hypothetial possibility evolves that stunning is not just an injury, but rather the unmasking of a regulatory mechanism to protect the heart against premature or further damage. The observation that coronary occlusion causes both stunning and preconditioning by a parallel, and not by a sequential, mechanism and that a multitude of genes alter their expression in order to protect the myocyte argue for a regulatory change.

Keywords

Xanthine Oxidase Ischemic Precondition Coronary Occlusion Stun Myocardium Xanthine Dehydrogenase 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bolli R. Mechanism of myocardial “stunning.” Circulation 1990; 82: 723–738.PubMedCrossRefGoogle Scholar
  2. 2.
    Glower D, Hoffmeister M, Newton JR, et al. Relationship between altered diastolic properties and systolic function after reversible ischemic injury (Abstr). Circulation 1983;68 (Suppl III):III253.Google Scholar
  3. 3.
    Stahl L, Aversano T, Becker L. Selective enhancement of function of stunned myocardium by increased flow. Circulation 1986; 74: 843–851.PubMedCrossRefGoogle Scholar
  4. 4.
    Ito B, Tate H, Kobayashi M, Schaper W. Reversibly injured, post-ischemic canine myocardium retains normal contractile reserve. Circ Res 1987; 61: 834–846PubMedGoogle Scholar
  5. 5.
    Heyndrickx G, Baig H, Nellens P, et al. Depression of regional blood flow and wall thickening after brief coronary occlusions. Am J Physiol 1979; 234: H653–H659.Google Scholar
  6. 6.
    Hearse D, Crome R, Yelion DM, Wyse R. Metabolic and flow correlates of myocardial ischaemia. Cardiovasc Res 1983; 17: 452–458.PubMedCrossRefGoogle Scholar
  7. 7.
    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. Circ Res 1985; 56: 220–230.PubMedGoogle Scholar
  8. 8.
    Greenfield R, Swain J. Disruption of myofibrillar energy use: Dual mechanisms that may contribute to post ischemic dysfunction in stunned myocardium. Circ Res 1987; 60: 283–289.PubMedGoogle Scholar
  9. 9.
    Neubauer S, Hamman BL, Perry SB, et al. Velocity of the creatine kinase reaction decreases in postischemic myocardium: A 31P-NMR magnetization transfer study of the isolated ferret heart. Circ Res 1988; 63: 1–15.PubMedGoogle Scholar
  10. 10.
    Swain J, Sabina RL, Hines JJ, et al. Repetitive episodes of brief ischaemia (12 min) do not produce a cumulative depletion of high energy phosphate compounds. Cardiovasc Res 1984; 18: 264–269.PubMedCrossRefGoogle Scholar
  11. 11.
    Hoffmeister HM, Mauser M, Sass S, et al. Ninety minutes of coronary occlusion: Prevention of infarcts by short intermittent reperfusion (Abstr). Circulation 1984;70(Suppl II):II261.Google Scholar
  12. 12.
    Hoffmeister HM, Mauser M, Sass S, Schaper W. Intermittent short time reperfusion prevents development of myocardial infarction (Abstr). J Mol Cell Cardiol 1984; 16 (Suppl II): 160.Google Scholar
  13. 13.
    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.PubMedGoogle Scholar
  14. 14.
    Murry C, Reimer KA, Long JB, Jennings RB. Reconditioning with ischemia protects ischemic myocardium (Abstr). Circulation 1985; 72 (Suppl III): 475.Google Scholar
  15. 15.
    Schott RJ, Rohmann S, Braun ER, Schaper W. Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 1990; 66: 1133–1142.PubMedGoogle Scholar
  16. 16.
    Schott RJ, Schaper W. Effects of transient coronary occlusion: Experience with myocardial stunning and preconditioning. Isr J Med Sci 1989; 25: 479–482.PubMedGoogle Scholar
  17. 17.
    Schaper W, Ito B. The energetics of “stunned” myocardium. In: deJong JW, ed. Myocardial Energy Metabolism. Martinus Nijhoff Publishers, Dordrecht: 1988: 203–213.CrossRefGoogle Scholar
  18. 18.
    Schaper W, Buchwald A, Hoffmeister HM, Ito B, et al. “Stunned” myocardium is a problem of energy utilization and not of energy supply (Abstr). Circulation 1985;72 (Suppl III):III119.Google Scholar
  19. 19.
    Becker L, Levine JH, DiPaula A, et al. Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation. J Am Coll Cardiol 1986; 7: 580–589.PubMedCrossRefGoogle Scholar
  20. 20.
    Krause S, Jacobus W, Becker L. Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic “stunned” myocardium (Abstr). Circulation 1986; 74 (Suppl II): 67.Google Scholar
  21. 21.
    Marban E, Litakaze M, Kusuoka H, et al. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci 1987; 84: 6005–6009.PubMedCrossRefGoogle Scholar
  22. 22.
    Kusuoka H, Koretsune Y, Chacko VP, et al. Excitation-contraction coupling in postischemic myocardium. Does failure of activator Cat` transients underlie stunning? Circ Res 1990; 66: 1268–1276.PubMedGoogle Scholar
  23. 23.
    Kobayashi M, Schmidt T, Schaper W. Regional myocardial oxygen consumption and segmental function in “stunned” myocardium of the pig (Abstr). Circulation 1987; 76 (Suppl IV): 1510.Google Scholar
  24. 24.
    Schaper W, Schott R, Kobayashi M. Reperfused myocardium. Stunning, preconditioning and reperfusion injury. In: Heusch G, ed. Pathophysiology and Rational Phannacotherapy of Myocardial Ischemia. Darmstadt: Steinkopff Verlag, 1990: 175–197.Google Scholar
  25. 25.
    Rohmann S, Schott RJ, Harting J, Schaper W. Ischemic preconditioning is not a function of stunned myocardium in swine (Abstr). Z Kardiol 1990; 79: 127.Google Scholar
  26. 26.
    Frass O. Gesteigerde Genexpression fur Calciumregulienende Proteine im Stunned myocardiun des Schweinherzens. Thesis, Giessen 1991.Google Scholar
  27. 27.
    Eddy LJ, Stewart JR, Jones HP, et al. Free radical-producing enzyme, xanthine oxidase, is undetectable in human hearts. Am J Physiol 1987; 253: H709–H711.PubMedGoogle Scholar
  28. 28.
    Flaig W, Braun W, Schaper W. Lack of xanthine and uric acid production in the pig heart during the following myocardial ischaemia (Abstr). J Mol Cell Cardiol 1986; 18 (Suppl II): 38.Google Scholar
  29. 29.
    Kehrer J, Piper H, Sies H. Xanthine oxidase is not responsible for reoxygenation injury in isolated-perfused rat heart. Free Rad Res Commun 1987; 3: 69–78.CrossRefGoogle Scholar
  30. 30.
    Muxfeldt M, Schaper W. The activity of xanthine oxidase in heart of pigs, guinea pigs, rabbits, rats, and humans. Basic Res Cardiol 1987; 82: 486–492.PubMedCrossRefGoogle Scholar
  31. 31.
    Podzuweit T, Braun W, Müller A, Schaper W. Xanthine oxidase-derived free oxygen radicals are not involved in the genesis of arrhythmias and infarction in the ischemic pig heart (Abstr). Fed Proc 1987; 46: 5774Google Scholar
  32. 32.
    Braun E, Rohmann S, Schott RJ, Schaper W. Superoxiddismutase (Sod) and Katalase (Kat) haben keinen Einfluß auf die Infarktgröße nach Praeconditionierung (Abstr). Z Kardiol 1990; 79: P130.Google Scholar
  33. 33.
    Vogelaers D, Degriek Y, Heyndrickx G. Failure of the iron chelator deferoxamine to improve functional recovery in stunned myocardium in a model of sequential coronary artery occlusion in conscious dogs (Abstr). Circulation 1990;82 (Suppl 1I0:1846.Google Scholar
  34. 34.
    Jarasch E, Grund C, Bruder G. Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium. Cell 1981; 25: 67–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Podzuweit T, Braun W, Müller A, Schaper W. Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals. Basic Res Cardiol 1987; 87: 493–505.CrossRefGoogle Scholar
  36. 36.
    Becker-Stötzel H, Podzuweit T, Schaper W. Aortenendothelien von Rind and Schwein unterscheiden sich wesentlich im Transport and Stoffwechsel von Purinen (Abstr). Z Kardiol 1989;78 (Suppl D:230.Google Scholar
  37. 37.
    McFalls EO, Pantely GA, Ophuis TO, et al. Relation of lactate production to postischemic reduction in function and myocardial oxygen consumption after partial coronary occlusion in swine (Abstr). Cardiovasc Res 1987; 21: 856–862.PubMedCrossRefGoogle Scholar
  38. 38.
    Laxson DD, Homans DC, Dai X, et al. Oxygen consumption and coronary reactivity in postischemic myocardium. Circ Res 1989; 64: 9–20.PubMedGoogle Scholar
  39. 39.
    Stahl L, Weiss H, Becker L. Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 1988; 77: 865–872.PubMedCrossRefGoogle Scholar
  40. 40.
    Bretschneider HJ, Cott LA, Hellige G, et al. A new hemodynamic parameter consisting of 5 additive determinants for estimation of the 02-consumption of the left ventricle. In: Proceedings of International Congress of Physiological Sciences,1971, München.Google Scholar
  41. 41.
    Rooke G, Feigl E. Work as a correlate of canine left ventricular oxygen consumption, and the problem of catecholamine oxygen wasting. Circ Res 1982; 50: 273–286.PubMedGoogle Scholar
  42. 42.
    Brunken R, Kottou S, Nienaber CA, et al. PET detection of viable tissue in myocardial segments with persistent defects at T1–201 SPECT. Radiology 1989; 172: 65–73.PubMedGoogle Scholar
  43. 43.
    Brand T, Rohmann S, Sharma HS, Schaper W. Protooncogene induction in the early phase of cardiac hypertrophy in rats (Abstr). Eur J Cell Biol 1989; 48 (Suppl 26): 16.Google Scholar
  44. 44.
    Fleischmann KE, Brand T, Sharma HS, et al. Gene expression in a preconditioning model (Abstr). Circulation 1990;82 (Suppl II0:III464.Google Scholar
  45. 45.
    Schlesinger M. Heat shock proteins. J Biol Chem 1990; 265: 12111–12114.PubMedGoogle Scholar
  46. 46.
    Schott R, Nao B, Strieter R, et al. Heat shock does not “precondition” canine myocardium (Abstr). Circulation 1990;82 (Suppl III):III464.Google Scholar
  47. 47.
    Schaper Jutta, Froede R, Buck A, Bleese N. Impaired myocardial ultrastructure and cytoskeleton in cardiomyopathic human myocardium. In: Schultheiß HP, ed. New Concepts in Viral Heart Disease, Berlin: Springer-Verlag, 1988: 295–302.Google Scholar
  48. 48.
    Schaper Jutta, Froede R, Hein S, et al. Ultrastructural changes and damage of the cytoskeleton in dilated cardiomyopathy (Abstr). J Mol Cell Cardiol 1989; 21 (Suppl IV): 46.Google Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • Wolfgang Schaper

There are no affiliations available

Personalised recommendations