Direct evidence that the hydroxyl radical plays a pathogenetic role in myocardial "stunning" in the conscious dog and demonstration that stunning can be markedly attenuated without subsequent adverse effects.
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Recent studies suggest that the hydroxyl radical (.OH) plays a pathogenetic role in postischemic ventricular dysfunction (myocardial stunning). This concept, however, is predicated exclusively on results obtained in anesthetized open-chest preparations, which are subject to the confounding influence of many unphysiological conditions and in which both myocardial stunning and free radical generation are greatly exaggerated. The lack of supporting evidence in more physiological animal models represents a major limitation of the .OH hypothesis of stunning. Furthermore, concern has been raised that myocardial stunning may be a period of rest necessary for full recovery, so that attenuation of the early phase of stunning by antioxidant therapy may have subsequent detrimental effects on the resting function and/or on the return of myocardial contractile reserve. To address these issues, in phase 1 of this study conscious unsedated dogs undergoing a 15-minute coronary artery occlusion received an intravenous...Keywords:
Stunning
Myocardial Stunning
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The hypothesis that mild decreases in myocardial function may occur with preservation of normal levels of intramyocardial ATP was tested. A model of single vessel coronary stenosis using eight mongrel dogs in an open chest preparation was used. Myocardial oxygen supply was altered by performing acute normovolemic hemodilution with a colloid solution. The results demonstrated significant alterations in myocardial ATP content with hemodilution-induced mild regional dysfunction, which was not in line with the hypothesized effects of ischemia on myocardial function. In addition, restoring myocardial function by minimal reinfusion of shed blood in this study did not restore myocardial energy stores, an effect that may be called metabolic stunning. The results suggest that myocardial stunning may not be an important and ubiquitous process during intraoperative myocardial ischemia. Further, myocardial function appears to be capable of quickly recovering from mild ischemia although metabolic function may be slower. Finally, the concept of decrements in myocardial function occurring in order to preserve myocardial metabolic stores does not appear to occur universally, which may be significant in the prevention or treatment of mild perioperative ischemia.
Myocardial Stunning
Stunning
Coronary circulation
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Myocardial Stunning
Stunning
Pathophysiology
Pathogenesis
Myocardial Reperfusion Injury
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Cardiac stunning refers to different dysfunctional levels occurring after an episode of acute ischemia, despite blood flow is near normal or normal. The phenomenon was initially identified in animal models, where it has been very well characterized. After being established in the experimental setting, it remained unclear, whether a similar syndrome occurs in humans. In addition, it remained controversial, whether stunning was of any clinical relevance as it is spontaneously reversible. Hence, many studies continue to focus on the properties and mechanisms of stunning, although therapies seem more relevant for attenuating and treating myocardial ischemia/reperfusion (I/R) injury, i.e. to bridge until recovery. This article reviews the different facets of cardiac stunning, i.e. myocardial, vascular/microvascular/endothelial, metabolic, neural/neuronal, and electrical stunning. This review also displays where these facets exist and which clinical relevance they might have. Particular attention is directed to the different therapeutic interventions that the various facets of this I/R-induced cardiac injury might require. A final outlook considers possible alternatives to further reduce the detrimental consequences of brief episodes of ischemia and reperfusion.
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Myocardial Stunning
Clinical Significance
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Myocardial Stunning
Stunning
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Myocardial Stunning
Stunning
Pathophysiology
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Stunning
Myocardial Stunning
Hibernating myocardium
Hibernation
Ventricular Function
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The phenomenon of myocardial stunning has been observed in all animal species studied. The possible occurrence of myocardial stunning in man has been demonstrated after either regional ischemia (such as exercise-induced angina, vasospastic or unstable angina) or after global ischemia (i.e., after cardioplegic arrest during cardiac surgery, or cardiac arrest, or heart transplantation). Finally, it may also be observed in patients with acute myocardial infarction, subjected to recanalization therapy, because viable myocardium, salvaged by reperfusion, may remain stunned, with delayed contractile recovery. Occurrence of stunning may aggravate hemodynamic conditions in already unstable patients, and it may lead to underestimation of the extent of myocardium salvaged by thrombolysis. Repeated episodes of stunning may lead to a condition of apparently 'chronic' contractile dysfunction that may be difficult to differentiate from hibernation, because of the technical difficulties in accurately measuring myocardial blood flow in patients, and because both phenomena may coexist and overlap in the same patient. In addition, recent evidence suggests that repeated episodes of stunning may lead to a progressive worsening of the residual contractile dysfunction and to longer recovery times, and it has thus been suggested, and it is much debated, that hibernation might at least in part be the consequence of repetitive episodes of stunning.
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Hibernating myocardium
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Dobutamine
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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.
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Myocardial stunning, or reversible postischemic ventricular dysfunction, occurs clinically much more frequently than was originally assumed when this phenomenon was first described in experimental studies. Despite the fact that stunned myocardium may appear histologically normal and have a normal metabolic profile, ventricular contractility is severely impaired. In a number of studies using both global and regional stunning models, we have demonstrated impaired oxygen extraction and abnormal patterns of oxygen consumption. In addition, impaired calcium transport or uptake by the sarcoplasmic reticulum occurs and there is sarcolemmal disruption during stunning despite reversibility of the ischemic injury. Although oxygen free radical production is thought to occur only early during postischemic reflow, the use of oxygen radical scavengers in a model of regional stunning was shown to attenuate the ventricular dysfunction.
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Myocardial Stunning
Contractility
Oxygen transport
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Cardiovascular research has led to the identification of three new and important phenomena: myocardial stunning, myocardial hibernation, and ischaemic preconditioning. Myocardial stunning is characterised by transient contractile dysfunction that persists after reperfusion despite the absence of irreversible damage and despite restoration of normal or near normal coronary blood flow. Myocardial hibernation is a condition of sustained reduction of contractile function in hypoperfused but viable myocardium, which recovers completely upon reperfusion. Ischaemic preconditioning refers to a phenomenon by which one or more brief periods of myocardial ischaemia increases the ischaemic tolerance against infarction by endogenous adaptive mechanisms.Current relevant literature obtained through PubMed search is reviewed with emphasis on occurrence of the phenomena, the therapeutic potential, and the underlying mechanisms.Several observations indicate that myocardial stunning, myocardial hibernation, and ischaemic preconditioning may occur in patients with coronary heart disease. Actually, an increasing amount of evidence indicates that these phenomena are of major importance with regard to myocardial ischaemic tolerance. The mechanisms underlying these phenomena are, however, not yet clarified.A better understanding of the mechanisms underlying myocardial stunning, myocardial hibernation, and ischaemic preconditioning may provide a rational basis for development of therapeutic interventions that increase myocardial ischaemic tolerance.
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Myocardial Stunning
Hibernation
Ischemic Preconditioning
Hibernating myocardium
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