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Mitochondrial Dysfunction in Cardiac Surgery. Mitochondria are key to the cellular response to energetic demand, but are also vital to reactive oxygen species signaling, calcium hemostasis, and regulation of cell death. Cardiac surgical patients with diabetes, heart failure, advanced age, or cardiomyopathies may have underlying mitochondrial dysfunction or be more sensitive to perioperative mitochondrial injury. Mitochondrial dysfunction, due to ischemia/reperfusion injury and an increased systemic inflammatory response due to exposure to cardiopulmonary bypass and surgical tissue trauma, impacts myocardial contractility and predisposes to arrhythmias. Strategies for perioperative mitochondrial protection and recovery include both well-established cardioprotective protocols and targeted therapies that remain under investigation.