Altered response of reperfused myocardium to repeated coronary occlusion in dogs

Schröder, Erwin; Kieso, Robert A.; Laughlin, Donald E.; Schröder, Marie; Meng, Ronald L.; Kerber, Richard E.

doi:10.1016/s0735-1097(87)80286-3

Cited by 26 publications

(2 citation statements)

References 31 publications

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“…[15][16][17][18][19] The largest decrease in contractility occurs after the first occlusion; with subsequent occlusions, the additional decrements in mechanical performance become progressively smaller. 20 (Whether repetitive ischemia also has a cumulative effect on the time to complete recovery, however, remains unclear.)…”

Section: Myocardial Stunning After Multiple Completely Reversible Iscmentioning

confidence: 99%

Mechanism of myocardial "stunning".

1990

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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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Section: Myocardial Stunning After Multiple Completely Reversible Iscmentioning

confidence: 99%

Mechanism of myocardial "stunning".

1990

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“…25 · 26 The second coronary occlusion unmasks abnormalities that may be latent. 25 This may be because of oxygen free radical toxicity. The hypokinesia may lead to hypoten sion, further increasing the likelihood of cellular necrosis.…”

Section: Transduction Defectmentioning

confidence: 99%

Can Myocardial Stunning Contribute to Myocardial Infarction During Coronary Artery Bypass Surgery?

Jain

1993

Journal of Cardiac Surgery

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Myocardial stunning commonly occurs after cardiopulmonary bypass (CPB). Myocardial stunning can be cardioprotective under some conditions, but in other situations may actually contribute to myocardial infarction (MI). Vascular endothelial stunning may be one of the mechanisms by which myocardial stunning can cause MI. It has been found that 15 minutes of reversible ischemia is enough to cause elevations in vascular resistance and impairment of vasodilator responsiveness. However, no correlation between contractile dysfunction and microvascular stunning has been observed. Transduction defects (increased oxygen extraction and consumption despite normal regional oxygen blood flow and delivery) may be another mechanism by which stunning predisposes to MI, indicating uncoupling of substrate utilization from energy production. In addition, abnormalities in wall motion, oxygen free radical toxicity, hypotension, use of inotropic agents (leading to increased oxygen consumption, high heart rates, and arrhythmias) increase the risk of cellular necrosis. Following CPB, flow limitations due to diffuse atherosclerosis in some areas may result in poor contractility, and newly grafted areas have a high probability of becoming ischemic and stunned. These areas are likely to contribute to MI.

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Effect of repetitive brief episodes of cardiac ischemia on ³¹P magnetic resonance spectroscopy in the cat

Holt

Wendland

Derugin

et al. 1990

Magnetic Resonance in Med

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Angina is characterized by brief periods of ischemia followed by reperfusion; the cumulative effect of these episodes on energetics of the myocardium has not been fully elucidated. This study used an in vivo feline model for the assessment of high-energy phosphate compounds during brief sequential periods of ischemia and reperfusion. Nine adult, open-chest, anesthetized cats were prepared with a reversible occluder around the proximal left anterior descending artery and a 1.2-cm-inside diameter coil sutured on the myocardial surface in the distribution of the left anterior descending coronary artery. Levels of PCr, Pi, and ATP (beta-phosphate signal) were measured by 31P MRS in a GE CSI 2-T NMR spectrometer/imager. Measurements were obtained during a control period and during three successive occlusion-deocclusion periods of roughly 12 and 20 min' duration, respectively. The last deocclusion period was observed for 60 min. Electron microscopy was performed in two animals. PCr declined (P less than 0.01) rapidly following each occlusion to 51 +/- 5.2% (occlusion 1), 53 +/- 5.8% (occlusion 2), and 48 +/- 5.7% (occlusion 3) of the control value by 6 min. Pi rose (P less than 0.01) with the three sequential occlusions to 253 +/- 46, 288 +/- 57, and 277 +/- 46%, respectively. PCr and Pi returned to baseline promptly with reperfusion, while ATP showed a gradual decline throughout the experiment, decreasing to 77 +/- 7.2% of control at the end of the last reperfusion (P less than 0.05). Although PCr returned to baseline during reperfusion, ATP did not, suggesting a reduction in the nucleotide pool. These findings indicate that the repeated episodes of ischemia, which are insufficient to produce necrosis, can have an effect on myocardial high-energy phosphate metabolism as evidenced by mild depletion of ATP.

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Altered response of reperfused myocardium to repeated coronary occlusion in dogs

Cited by 26 publications

References 31 publications

Mechanism of myocardial "stunning".

Mechanism of myocardial "stunning".

Can Myocardial Stunning Contribute to Myocardial Infarction During Coronary Artery Bypass Surgery?

Effect of repetitive brief episodes of cardiac ischemia on ³¹P magnetic resonance spectroscopy in the cat

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Altered response of reperfused myocardium to repeated coronary occlusion in dogs

Cited by 26 publications

References 31 publications

Mechanism of myocardial "stunning".

Mechanism of myocardial "stunning".

Can Myocardial Stunning Contribute to Myocardial Infarction During Coronary Artery Bypass Surgery?

Effect of repetitive brief episodes of cardiac ischemia on 31P magnetic resonance spectroscopy in the cat

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Effect of repetitive brief episodes of cardiac ischemia on ³¹P magnetic resonance spectroscopy in the cat