Mitochondrial Dysfunction in Cardiac Surgery

Abstract

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.

Keywords: Cardiac surgery; Cardioprotection; Cardiopulmonary bypass; Inflammation; Ischemia/reperfusion injury; Mitochondria; Myocardial metabolism.

Fig. 1.

Perioperative I/R and inflammation induce oxidative stress (reactive oxygen and nitrogen species), which modulate MQC programs through redox signaling. Excessive oxidative stress may also contribute to mitochondrial dysfunction, resulting in energetic failure and cell death. RNS, reactive nitrogen species.

Fig. 2.

Hypothesis for the mechanism of age-related progression of oxidative phosphorylation (OXPHOS) diseases. The upper panel shows the proposed accumulation of somatic mtDNA mutations with age.^, Patients are born with a certain percentage of mutant mtDNAs, some patients with more than others. The dashed lines indicate the relative ages when sufficient mutations accumulate to cause disease. The lower panel shows the decline of OXPHOS capacity of healthy individuals and patients with underlying mtDNA mutations. Different tissues have different minimum energy thresholds, below which dysfunction is clinically apparent, shown by dashed lines. OXPHOS declines for both healthy individuals and patients, consistent with the accumulation of somatic mtDNA damage. However, because of the inherited mtDNA mutation, patients start with a lower initial OXPHOS capacity and thus drop below the expression thresholds much earlier than normal individuals. (From Wallace DC. Diseases of the mitochondrial DNA. Annu Rev Biochem 1992;61:1175–212; with permission.)