Oxygen-derived free radicals and postischemic myocardial dysfunction ("stunned myocardium")

Roberto Bolli

Research output: Contribution to journalReview article

Abstract

Experimental studies have demonstrated that myocardium reperfused after reversible ischemia exhibits prolonged depression of contractile function ("stunning"), which is associated with various ultrastructural, biochemical, vascular and other functional abnormalities. Clinical observations suggest that stunning occurs in many situations (for example, rest and exercise-induced angina, myocardial infarction with early reperfusion, open heart surgery, transplantation) and thus may contribute significantly to morbidity among patients with coronary artery disease. In recent years an increasing number of studies have provided indirect evidence that postischemic myocardial dysfunction may be mediated in part by the generation of reactive oxygen species, such as superoxide radical (· O2-), hydrogen peroxide (H2O2) and hydroxyl radical (· OH). Thus, it has been shown that the recovery of the stunned myocardium is enhanced by agents that either scavenge oxygen metabolites, such as superoxide dismutase and catalase, N-2-mercaptopropionylglycine and dimethylthiourea, or prevent their generation, such as allopurinol, oxypurinol and desferrioxamine. More recent experiments utilizing electron paramagnetic resonance spectroscopy have directly demonstrated that reperfusion after a reversible ischemic episode is associated with a burst of free radical production. At present, the evidence supporting the free radical hypothesis is suggestive but not conclusive. Definitive demonstration of the role of oxy-radicals will require careful studies measuring the production of these species is conscious animal models of postischemic dysfunction. If confirmed, the free radical hypothesis will provide not only new important insights into the pathophysiology of ischemic injury, but also a rationale for developing clinically applicable interventions.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalJournal of the American College of Cardiology
Volume12
Issue number1
DOIs
StatePublished - Jul 1988

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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