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Novel Mechanisms Mediating Stunned Myocardium

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Abstract

Myocardial stunning is defined as the prolonged contractile dysfunction following an ischemic episode that does not result in necrosis, which also occurs in patients with coronary artery disease. There is also evidence to consider myocardial stunning as a fundamental component of hibernating myocardium. Various experimental approaches (from a brief episode to prolonged partial ischemia) and animal models (from rodents to large mammals) have been developed to investigate the pathogenesis of myocardial stunning. Three hypotheses to explain the mechanism, i.e. oxygen radical, Troponin I degradation, and Ca2+, have been proposed. The first was tested primarily using large mammalian models, whereas the others were tested primarily using rodent models. Recently, the Ca2+ handling hyothesis has been tested in a large mammalian swine model of myocardial stunning, in which both Ca2+ and transients and L-type Ca2+ current density were decreased. Relaxation function and phospholamban phosphorylation are also radically different in large mammalian and rodent models. In addition, troponin I degradation, which was identified as the mechanism of stunning in rodent models, was not found in stunned swine myocardium. Interestingly, the large mammalian model demonstrates that stunning elicits broad changes in gene and protein regulation, some of which have not been observed in the heart previously. The overall genomic adaptation upregulates the expression of survival genes that prevent irreversible damage. Pursuing these new concepts derived from large mammalian models of ischemia/reperfusion will provide more comprehensive mechanistic information underlying myocardial stunning and will serve to devise new therapeutic modalities for patients.

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  1. Department of Cell Biology and Molecular Medicine, Department of Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ

    Song-Jung Kim, Christophe Depre & Stephen F. Vatner

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Kim, SJ., Depre, C. & Vatner, S.F. Novel Mechanisms Mediating Stunned Myocardium. Heart Fail Rev 8, 143–153 (2003). https://doi.org/10.1023/A:1023040718319

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