Endogenous factors contributing to ischemia-reperfusion injury. Following ischemia, blood flow is reestablished in the myocardium. The myocardium is subject to a number of abrupt changes during the transition from ischemia to reperfusion. Both biochemical and metabolic alterations occur including the generation of reactive oxygen species (ROS), decrease in ATP levels, an increase in inflammatory mediators, the rapid restoration of physiological pH, which in turn increases intracellular sodium and overload of intracellular calcium and mitochondrial calcium. These factors interact with each other to mediate reperfusion injury through the opening of the mitochondrial permeability transition pore (mPTP) and initiation of cell death pathways .