Circulation, Vol 82, 723-738, Copyright © 1990 by American Heart Association
R Bolli
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.
ARTICLES
Mechanism of myocardial "stunning"
Department of Medicine, Baylor College of Medicine, Houston, Tex 77030.
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