Mitochondria represent one-third of the mass of the heart and play a critical role in maintaining cellular functions. However, mitochondria are also a source of reactive oxygen species (ROS) and can be involved in all form of cell death. Clearly the prolonged mitochondrial permeability transition pore (mPTP) opening is a triggering event in I/R injury. Therefore, it is not surprising that cardioprotective mechanisms may act by opposing mitochondrial cell death pathways.

Cardioprotective pathways against I/R injury are activated by stimuli such as ischemic or pharmacological preconditioning (PreC) and postconditioning (PostC) and converge on mitochondria preserving their function. The protective effects observed with PostC are comparable to those observed with PreC and have salubrious effects on different cell types within the heart (cardiomyocytes, endothelium). PostC protects against necrosis, apoptosis, contractile dysfunction, arrhythmias and microvascular injury or 'no-reflow'. The mechanisms by which PostC alters the pathophysiology of I/R injury involves physiological mechanisms (e.g., delaying realkalinization of tissue pH, triggering release of autacoids, ROS signaling, modulation of various channels such as ATP-dependent K+ channels and mPTP formation) and molecular mechanisms (e.g., activation of RISK and SAFE pathways). Protection is also accomplished by the dynamic interplay of fusion, fission, autophagy, and mitochondrial biogenesis.