Cardiovascular Drugs and Therapy

, Volume 5, Supplement 2, pp 249–268

Oxygen-derived free radicals and myocardial reperfusion injury: An overview

  • Roberto Bolli
Reperfusion Injury: Does It Exist and Can It Be Manipulated?

DOI: 10.1007/BF00054747

Cite this article as:
Bolli, R. Cardiovasc Drug Ther (1991) 5: 249. doi:10.1007/BF00054747


Reperfusion of acutely ischemic myocardium is associated with various distinctive pathophysiologic derangements, which are collectively referred to as reperfusion injury. Among these, three have been atributed to oxygen radicals: a) arrhythmias, b) transient mechanical dysfunction (“stunning”), and c) cell death. a) Reperfusion-induced arrhythmias. Although the precise mechanism for reperfusion arrhythmias remains to be determined, considerable evidence suggests that oxygen radicals play an important pathogenetic role in these rhythm disturbances. b) Transient mechanical dysfunction (“myocardial stunning”). Studies suggest that this abnormality is caused by events occurring in the initial seconds of reperfusion, and therefore represents a manifestation of sublethal, reversible reperfusion injury. Although our understanding of the mechanism of myocardial stunning is still fragmentary, there is overwhelming evidence for a pathogenetic role of oxygen radicals. c) Cell death. The evidence that reperfusion causes extension of the infarct produced by the antecedent ischemia is highly controversial. Although several studies have reported reduction of infarct size with antioxidants applied at the time of reperfusion, numerous other investigations have failed to reproduce these results. At present, there is no obvious explanation for this discrepancy. What is clear is that short-term administration of antioxidants at the time of reperfusion will not produce sustained limitation of infarct size. However, the possibility that long-term administration of antioxidants will produce sustained limitation of infarct size merits further consideration. In conclusion, there is strong evidence that the generation of oxygen radicals upon reperfusion plays an important pathogenetic role in two manifestations of reperfusion injury, namely, arrhythmias and stunning. Intense controversy persists regarding whether oxygen radicals contribute to extending cell death upon reperfusion and whether reperfusion in itself causes cell death. On the basis of the evidence available at this time, oxygen radicals appear to be important in the genesis of relatively mild, sublethal forms of myocellular damage, but their role in the genesis of lethal myocellular injury remains to be established.

Key Words

oxygen free radicalscoronary reperfusionmyocardial ischemiareperfusion arrhythmiasmyocardial infarctionelectron paramagnetic resonance spectroscopyspin trappingpostischemic dysfunctionlipid peroxidationcalcium homeostasis

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Roberto Bolli
    • 1
  1. 1.Experimental Animal Laboratory, Section of Cardiology, Department of MedicineBaylor College of MedicineHoustonUSA
  2. 2.Section of CardiologyBaylor College of MedicineHouston