Molecular and cellular mechanisms of myocardial stunning
- PMID: 10221990
- DOI: 10.1152/physrev.1999.79.2.609
Molecular and cellular mechanisms of myocardial stunning
Abstract
The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a single entity but rather as a "syndrome" that has been observed in a wide variety of experimental settings, which include the following: 1) stunning after a single, completely reversible episode of regional ischemia in vivo; 2) stunning after multiple, completely reversible episodes of regional ischemia in vivo; 3) stunning after a partly reversible episode of regional ischemia in vivo (subendocardial infarction); 4) stunning after global ischemia in vitro; 5) stunning after global ischemia in vivo; and 6) stunning after exercise-induced ischemia (high-flow ischemia). Whether these settings share a common mechanism is unknown. Although the pathogenesis of myocardial stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals (oxyradical hypothesis) and by a transient calcium overload (calcium hypothesis) on reperfusion. The final lesion responsible for the contractile depression appears to be a decreased responsiveness of contractile filaments to calcium. Recent evidence suggests that calcium overload may activate calpains, resulting in selective proteolysis of myofibrils; the time required for resynthesis of damaged proteins would explain in part the delayed recovery of function in stunned myocardium. The oxyradical and calcium hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, increased free radical formation could cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. Free radical generation could also directly alter contractile filaments in a manner that renders them less responsive to calcium (e.g., oxidation of critical thiol groups). However, it remains unknown whether oxyradicals play a role in all forms of stunning and whether the calcium hypothesis is applicable to stunning in vivo. Nevertheless, it is clear that the lesion responsible for myocardial stunning occurs, at least in part, after reperfusion so that this contractile dysfunction can be viewed, in part, as a form of "reperfusion injury." An important implication of the phenomenon of myocardial stunning is that so-called chronic hibernation may in fact be the result of repetitive episodes of stunning, which have a cumulative effect and cause protracted postischemic dysfunction. A better understanding of myocardial stunning will expand our knowledge of the pathophysiology of myocardial ischemia and provide a rationale for developing new therapeutic strategies designed to prevent postischemic dysfunction in patients.
Similar articles
-
Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1.Circulation. 2001 Dec 11;104(24):2981-9. doi: 10.1161/hc4801.100038. Circulation. 2001. PMID: 11739316 Review.
-
[Reversible left ventricular dysfunction in coronary disease (part one): myocardial stunning].Med Pregl. 2000 Jan-Feb;53(1-2):39-44. Med Pregl. 2000. PMID: 10953549 Review. Serbian.
-
Basic and clinical aspects of myocardial stunning.Prog Cardiovasc Dis. 1998 May-Jun;40(6):477-516. doi: 10.1016/s0033-0620(98)80001-7. Prog Cardiovasc Dis. 1998. PMID: 9647607 Review.
-
Mechanism of myocardial "stunning".Circulation. 1990 Sep;82(3):723-38. doi: 10.1161/01.cir.82.3.723. Circulation. 1990. PMID: 2203553 Review.
-
[Hibernation, stunning, ischemic preconditioning--new paradigms in coronary disease?].Z Kardiol. 1992 Nov;81(11):596-609. Z Kardiol. 1992. PMID: 1471397 Review. German.
Cited by
-
Myocardial Ischemia-Reperfusion Injury: Unraveling Pathophysiology, Clinical Manifestations, and Emerging Prevention Strategies.Biomedicines. 2024 Apr 4;12(4):802. doi: 10.3390/biomedicines12040802. Biomedicines. 2024. PMID: 38672157 Free PMC article. Review.
-
Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.Front Cardiovasc Med. 2024 Mar 15;11:1376367. doi: 10.3389/fcvm.2024.1376367. eCollection 2024. Front Cardiovasc Med. 2024. PMID: 38559672 Free PMC article.
-
Data-Independent Acquisition Proteomics and N-Terminomics Methods Reveal Alterations in Mitochondrial Function and Metabolism in Ischemic-Reperfused Hearts.J Proteome Res. 2024 Feb 2;23(2):844-856. doi: 10.1021/acs.jproteome.3c00754. Epub 2024 Jan 24. J Proteome Res. 2024. PMID: 38264990
-
Simultaneous assessment of mechanical and electrical function in Langendorff-perfused ex-vivo mouse hearts.Front Cardiovasc Med. 2023 Nov 8;10:1293032. doi: 10.3389/fcvm.2023.1293032. eCollection 2023. Front Cardiovasc Med. 2023. PMID: 38028448 Free PMC article.
-
The roles of intracellular proteolysis in cardiac ischemia-reperfusion injury.Basic Res Cardiol. 2023 Sep 28;118(1):38. doi: 10.1007/s00395-023-01007-z. Basic Res Cardiol. 2023. PMID: 37768438 Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous