Abnormal mitochondrial function during ischemia reperfusion provides targets for pharmacological therapy.

The concept of reperfusion injury has been a subject of intense debate. Some researchers believe that the entire injury develops during the ischemic period, whereas others argue that blood reflow extends tissue injury due to the release of oxygen-derived free radicals, an inflammatory reaction involving influx of various populations of immune cell, and dysregulation of intracellular and particularly mitochondrial calcium concentration. Mitochondrial calcium overload in the presence of oxygen-derived free radicals can result in the opening of the mitochondrial permeability transition pore (mPTP), which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis lead to a rupture of the plasma membrane and cell death. Mitochondria have long been proposed as one of the main players in cell death, since the mitochondria are central to synthesis of both ATP and the formation of oxygen-derived free radicals. These mechanisms are centered on mitochondrial calcium overload as a key component of cell death. Pharmacological strategies that are cardioprotective attempt to reduce mitochondrial calcium overload to decrease the likelihood of arrhythmias and cardiac dysfunction elicited by reperfusion.