Circulation, Vol 82, 723-738, Copyright © 1990 by American Heart Association
R Bolli
Among the numerous mechanisms proposed for myocardial stunning, three
appear to be more plausible: 1) generation of oxygen radicals, 2) calcium
overload, and 3) excitation-contraction uncoupling. First, the evidence for
a pathogenetic role of oxygen-derived free radicals in myocardial stunning
is overwhelming. In the setting of a single 15- minute coronary occlusion,
mitigation of stunning by antioxidants has been reproducibly observed by
several independent laboratories. Similar protection has been recently
demonstrated in the conscious animal, that is, in the most physiological
experimental preparation available. Furthermore, generation of free
radicals in the stunned myocardium has been directly demonstrated by spin
trapping techniques, and attenuation of free radical generation has been
repeatedly shown to result in attenuation of contractile dysfunction.
Numerous observations suggest that oxyradicals also contribute to stunning
in other settings: after global ischemia in vitro, after global ischemia
during cardioplegic arrest in vivo, and after multiple brief episodes of
regional ischemia in vivo. Compelling evidence indicates that the critical
free radical damage occurs in the initial moments of reflow, so that
myocardial stunning can be viewed as a sublethal form of
oxyradical-mediated "reperfusion injury." Second, there is also
considerable evidence that a transient calcium overload during early
reperfusion contributes to postischemic dysfunction in vitro; however, the
importance of this mechanism in vivo remains to be defined. Third,
inadequate release of calcium by the sarcoplasmic reticulum, with
consequent excitation- contraction uncoupling, may occur after multiple
brief episodes of regional ischemia, but its role in other forms of
postischemic dysfunction has not been explored. It is probable that
multiple mechanisms contribute to the pathogenesis of myocardial stunning.
The three hypotheses outlined above are not mutually exclusive and in fact
may represent different steps of the same pathophysiological cascade. Thus,
generation of oxyradicals may cause sarcoplasmic reticulum dysfunction, and
both of these processes may lead to calcium overload, which in turn could
exacerbate the damage initiated by oxygen species. The concepts discussed
in this review should provide not only a conceptual framework for further
investigation of the pathophysiology of reversible ischemia-reperfusion
injury but also a rationale for developing clinically applicable
interventions designed to prevent postischemic ventricular dysfunction.
ARTICLES
Mechanism of myocardial "stunning"
Department of Medicine, Baylor College of Medicine, Houston, Tex 77030.
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A. M. Jayawant, E. R. Stephenson Jr, G. S. Matte, G. A. Prophet, K. F. LaNoue, J. W. Griffith, and R. J. Damiano Jr Potassium-channel opener cardioplegia is superior to St. Thomas’ solution in the intact animal Ann. Thorac. Surg., July 1, 1999; 68(1): 67 - 74. [Abstract] [Full Text] [PDF]
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 B. Ostadal, I. Ostadalova, and N. S. Dhalla Development of Cardiac Sensitivity to Oxygen Deficiency: Comparative and Ontogenetic Aspects Physiol Rev, July 1, 1999; 79(3): 635 - 659. [Abstract] [Full Text] [PDF]
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L. C. Becker, R. W. Jeremy, J. Schaper, and W. Schaper Ultrastructural assessment of myocardial necrosis occurring during ischemia and 3-h reperfusion in the dog Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H243 - H252. [Abstract] [Full Text] [PDF]
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H. Schad, W. Heimisch, G. P. Eising, and N. Mendler Effect of dopamine and atrial pacing on stunned myocardium Eur. J. Cardiothorac. Surg., June 1, 1999; 13(6): 710 - 717. [Abstract] [Full Text] [PDF]
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J. M.J. Lamers Preconditioning and limitation of stunning: one step closer to the protected protein(s)? Cardiovasc Res, June 1, 1999; 42(3): 571 - 575. [Full Text] [PDF]
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N. G. Perez, E. Marban, and H. E Cingolani Preservation of myofilament calcium responsiveness underlies protection against myocardial stunning by ischemic preconditioning Cardiovasc Res, June 1, 1999; 42(3): 636 - 643. [Abstract] [Full Text] [PDF]
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X.-S. Cheng, H. Shimokawa, H. Momii, J.-i. Oyama, N. Fukuyama, K. Egashira, H. Nakazawa, and A. Takeshita Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo Cardiovasc Res, June 1, 1999; 42(3): 651 - 659. [Abstract] [Full Text] [PDF]
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 S. Ishihara, J. A. Ward, O. Tasaki, B. A. Pruitt Jr., M. A. Javors, R. A. Cassidy, and D. W. Mozingo Biphasic changes in left ventricular function during hyperdynamic endotoxemia Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1999; 276(5): R1516 - R1524. [Abstract] [Full Text] [PDF]
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R. Bolli and E. Marban Molecular and Cellular Mechanisms of Myocardial Stunning Physiol Rev, April 1, 1999; 79(2): 609 - 634. [Abstract] [Full Text] [PDF]
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A. M. Jayawant, E. R. Stephenson Jr, and R. J. Damiano Jr 2,3-Butanedione monoxime cardioplegia: advantages over hyperkalemia in blood-perfused isolated hearts Ann. Thorac. Surg., March 1, 1999; 67(3): 618 - 623. [Abstract] [Full Text] [PDF]
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T W Koh, G S Carr-White, A C DeSouza, F D Ferdinand, J R Pepper, and D G Gibson Effect of coronary occlusion on left ventricular function with and without collateral supply during beating heart coronary artery surgery Heart, March 1, 1999; 81(3): 285 - 291. [Abstract] [Full Text]
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 M. F. Di Carli, J. Maddahi, S. Rokhsar, H. R. Schelbert, D. Bianco-Batlles, R. C. Brunken, and B. Fromm LONG-TERM SURVIVAL OF PATIENTS WITH CORONARY ARTERY DISEASE AND LEFT VENTRICULAR DYSFUNCTION: IMPLICATIONS FOR THE ROLE OF MYOCARDIAL VIABILITY ASSESSMENT IN MANAGEMENT DECISIONS J. Thorac. Cardiovasc. Surg., December 1, 1998; 116(6): 997 - 1004. [Abstract] [Full Text] [PDF]
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A. M. Jayawant and R. J. Damiano Jr The superiority of pinacidil over adenosine cardioplegia in blood-perfused isolated hearts Ann. Thorac. Surg., October 1, 1998; 66(4): 1329 - 1335. [Abstract] [Full Text] [PDF]
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E. Mori, N. Haramaki, H. Ikeda, and T. Imaizumi Intra-coronary administration of L-arginine aggravates myocardial stunning through production of peroxynitrite in dogs Cardiovasc Res, October 1, 1998; 40(1): 113 - 113. [Abstract] [Full Text] [PDF]
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M. B. Vroom Pharmacologic Management of Acute Heart Failure: A Review Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 1998; 2(3): 191 - 203. [Abstract] [PDF]
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C. A. Rinaldi, A. Z. Linka, N. D. Masani, P. G. Avery, E. Jones, H. Saunders, and R. J. C. Hall Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning Circulation, August 25, 1998; 98(8): 749 - 756. [Abstract] [Full Text] [PDF]
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N. G. Perez, W. D. Gao, and E. Marban Novel Myofilament Ca2+-Sensitizing Property of Xanthine Oxidase Inhibitors Circ. Res., August 24, 1998; 83(4): 423 - 430. [Abstract] [Full Text] [PDF]
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M. Uematsu, G. R. Gaudette, J. O. Laurikka, S. Levitsky, and J. D. McCully Adenosine-enhanced ischemic preconditioning decreases infarct in the regional ischemic sheep heart Ann. Thorac. Surg., August 1, 1998; 66(2): 382 - 387. [Abstract] [Full Text] [PDF]
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M. Jayawant, E. R. Stephenson Jr., and R. J. Damiano Jr. Advantages of continuous hyperpolarized arrest with pinacidil over St. Thomas' hospital solution during prolonged ischemia J. Thorac. Cardiovasc. Surg., July 1, 1998; 116(1): 131 - 138. [Abstract] [Full Text]
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N. A. McHugh, G. F. Merrill, and S. R. Powell Estrogen diminishes postischemic hydroxyl radical production Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H1950 - H1954. [Abstract] [Full Text] [PDF]
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A. Sabri, K. L. Byron, A. M. Samarel, J. Bell, and P. A. Lucchesi Hydrogen Peroxide Activates Mitogen-Activated Protein Kinases and Na+-H+ Exchange in Neonatal Rat Cardiac Myocytes Circ. Res., June 1, 1998; 82(10): 1053 - 1062. [Abstract] [Full Text] [PDF]
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D. J Duncker, R. Schulz, R. Ferrari, D. Garcia-Dorado, C. Guarnieri, G. Heusch, and P. D Verdouw "Myocardial stunning": remaining questions Cardiovasc Res, June 1, 1998; 38(3): 549 - 558. [Full Text] [PDF]
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R. A. Kloner, R. Bolli, E. Marban, L. Reinlib, and E. Braunwald Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning : An NHLBI Workshop Circulation, May 19, 1998; 97(18): 1848 - 1867. [Full Text] [PDF]
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