Mechanisms of myocardial “stunning”

Bolli, R.

doi:10.1016/1053-0770(91)90347-v

Cited by 33 publications

(14 citation statements)

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“…Com- parisons of infarct size alone may underestimate the effects of POC-mediated attenuation of reperfusion injury because infarct size does not reflect the impact of myocardial stunning. Moreover, measurements of cardiac mechanical performance incorporate more of the immediate effects of reperfusioninduced cardiac dysfunction, such as dysrhythmias and stunning (3).…”

Section: Discussionmentioning

confidence: 99%

Regulating RISK: a role for JAK-STAT signaling in postconditioning?

Goodman¹,

Koch²,

Fuller-Bicer³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Postconditioning (POC), a novel strategy of cardioprotection against ischemia-reperfusion injury, is clinically attractive because of its therapeutic application at the predictable onset of reperfusion. POC activates several intracellular kinase signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt (RISK). The regulation of POC-induced survival kinase signaling, however, has not been fully characterized. JAK-STAT activation is integral to cardiac ischemic tolerance and may provide upstream regulation of RISK. We hypothesized that POC requires the activation of both JAK-STAT and RISK signaling. Langendorff-perfused mouse hearts were subjected to 30 min of global ischemia and 40 min of reperfusion, with or without POC immediately after ischemia. A separate group of POC hearts was treated with AG 490, a JAK2 inhibitor, Stattic, a specific STAT3 inhibitor, or LY-294002, a PI3K inhibitor, at the onset of reperfusion. Cardiomyocyte-specific STAT3 knockout (KO) hearts were also subjected to non-POC or POC protocols. Myocardial performance (+dP/dt(max), mmHg/s) was assessed throughout each perfusion protocol. Phosphorylated (p-) STAT3 and Akt expression was analyzed by Western immunoblotting. POC enhanced myocardial functional recovery and increased expression of p-STAT3 and p-Akt. JAK-STAT inhibition abrogated POC-induced functional protection. STAT3 inhibition decreased expression of both p-STAT3 and p-Akt. PI3K inhibition also attenuated POC-induced cardioprotection and reduced p-Akt expression but had no effect on STAT3 phosphorylation. Interestingly, STAT3 KO hearts undergoing POC exhibited improved ischemic tolerance compared with KO non-POC hearts. POC induces myocardial functional protection by activating the RISK pathway. JAK-STAT signaling, however, is insufficient for effective POC without PI3K-Akt activation.

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Section: Discussionmentioning

confidence: 99%

Regulating RISK: a role for JAK-STAT signaling in postconditioning?

Goodman¹,

Koch²,

Fuller-Bicer³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Recently, we and others have reported that brief periods of ischemia leave myocardium stunned without cellular necrosis. 3,4,10 Stunning swine myocardium with two cycles of a 10 min left anterior descending coronary artery (LAD) occlusion followed by reperfusion increases tolerance to a subsequent longer period (60 min) of ischemia. 6 To get an insight into the myocardial molecular response in ischemic reperfused swine myocardium, we studied the expression pattern of a number of genes which could play a pivotal role in cytoprotection and adaptation in the heart.…”

Section: Molecular Phenotype Of Reperfused Myocardiummentioning

confidence: 99%

“…1,2 The occurrence of myocardial infarction during an acute coronary occlusion indicates not only the lack of oxygen and blood supply but also the disruption of defense and adaptive mechanisms of the myocardium against ischemia. Myocardial responses to a critical coronary stenosis in terms of adaptation and defense could be (1) long lasting (hours to days) contractile dysfunction in the absence of any cell death (stunned myocardium); 3,4 (2) tolerance towards ischemia after a short period of supply ±demand mismatch (preconditioned myocardium); 5,6 (3) myocardial angiogenesis i.e. growth of blood vessels and development of collateral circulation; 7,8 and nally, (4) atrophy of cardiac myocytes in chronic coronary artery disease.…”

mentioning

confidence: 99%

Role of cytokines in myocardial ischemia and reperfusion

Sharma

Das

1997

Mediators of Inflammation

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Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

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“…Reperfusion itself, however, may have deleterious effects on the myocardial fiber, including microvascular damage and cellular necrosis, as well as undesirable clinical manifestations such as myocardial stunning and arrhythmias (2,3). During the first hours of AMI, there is an increase in catecholamine secretion, an increase in circulating free fatty acids, and glucose intolerance (4 -6).…”

mentioning

confidence: 99%