The Role of Superoxide in Heart Disease
James J. Galvez and R. Mark Payne

Is a common event in human pathophysiology. Ischemia occurs when blood flow has slowed,
or stopped, and cannot meet the metabolic demands of the tissues. This happens, for
example, in the event of stroke or heart attack. It also happens in the more predictable
settings of surgery, such as coronary by-pass operations where the heart is turned off while the
surgeon works, or during transplant of an organ where there is a prolonged period of ischemia
while the donor organ is transported to the recipient. The extent of injury associated with
ischemia is directly correlated to the magnitude and duration of the ischemic event and the
collateral circulation of the affected tissue.1-3 Reperfusion takes place when blood flow is reestablished
and the organ(s) receives enough blood flow to meet its metabolic demands. This is a
desirable outcome for victims of heart attack and stroke since without reperfusion the affected
tissues will die. Ironically, reperfusion is also associated with significant tissue injury from the
generation of free radicals, and from ion imbalance, particularly calcium. Generation of superoxide
(O2?-) is a key event that occurs with reperfusion and can lead to a cascade of free radical
production that damages cellular function. This damage to the cell can initiate cell death as a
primary outcome via apoptosis or inflammation, or it may lead to cumulative damage with a
decrease in cellular function over time.