Mitochondrial Dysfunction in Atrial Tissue of Patients Developing Postoperative Atrial Fibrillation.

Background: Mitochondria are the major site of cellular oxidation. Metabolism and oxidative stress have been implicated as possible mechanisms for postoperative atrial fibrillation (POAF) after cardiac operations. Establishing the precise nature of mitochondrial dysfunction as an etiologic factor for oxidative stress-related cell death and apoptosis could further the understanding of POAF. To establish this relationship, mitochondrial function was studied in patients undergoing cardiac operations that developed POAF and compared it with patients without POAF.

Methods: Right atrial tissue and serum samples were collected from 85 patients before and after cardiopulmonary bypass. Microarray analysis (36 patients) and RNA sequencing (5 patients) were performed on serum and atrial tissues, respectively, for identifying significantly altered genes in patients who developed POAF. On the basis of these results, Western blot was performed in 52 patients for the genes that were most altered, and functional pathways were established.

Results: POAF developed in 30.6% (n = 26) of patients. Serum microarray showed significant fold changes in the expression of 49 genes involved in inflammatory response, oxidative stress, apoptosis, and amyloidosis (p < 0.05) in the POAF group. Similarly, RNA sequencing demonstrated an increased expression of genes associated with inflammatory response, fatty acid metabolism, and apoptosis in the POAF group (false discovery rate > 0.05). Immunoblotting showed a significant increase in TNFAIP6 (tumor necrosis factor, α-induced protein 6; p = 0.02) and transforming growth factor-β (p = 0.04) after cardiopulmonary bypass in the POAF group. There was a significant decrease in PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α; p = 0.002) and CPT1 (carnitine palmitoyltransferase I; p < 0.0005) in the POAF group after cardiopulmonary bypass.

Conclusions: Compared with patients without POAF, those with POAF demonstrated mitochondrial dysfunction at various levels that are suitable for potential pharmacotherapy.