Minimized Extracorporeal Circulation Is Associated with Reduced Plasma Levels of Free-Circulating Mitochondrial DNA Compared to Conventional Cardiopulmonary Bypass: A Secondary Analysis of an Exploratory, Prospective, Interventional Study

Abstract

The use of minimized extracorporeal circulation (MiECC) during cardiac surgery is associated with a reduced inflammatory reaction compared to conventional cardiopulmonary bypass (cCPB). Since it is unknown if MiECC also reduces the amount of free-circulating mitochondrial DNA (mtDNA), this study aims to compare MiECC-induced mtDNA release to that of cCPB as well as to identify potential relations between the plasma levels of mtDNA and an adverse outcome. Overall, 45 patients undergoing cardiac surgery with either cCPB or MiECC were included in the study. MtDNA encoding for NADH dehydrogenase 1 was quantified with quantitative polymerase chain reaction. The plasma amount of mtDNA was significantly lower in patients undergoing cardiac surgery with MiECC compared to cCPB (MiECC: 161.8 (65.5–501.9); cCPB 190.8 (82–705.7); p < 0.001). Plasma levels of mtDNA showed comparable kinetics independently of the study group and peaked during CPB (MiECC preoperative: 68.2 (26.5–104.9); MiECC 60 min after start of CPB: 536.5 (215.7–919.6); cCPB preoperative: 152.5 (80.9–207.6); cCPB 60 min after start of CPB: 1818.0 (844.2–3932.2); all p < 0.001). Patients offering an mtDNA blood concentration of >650 copies/µL after the commencement of CPB had a 5-fold higher risk for postoperative atrial fibrillation independently of the type of cardiopulmonary bypass. An amount of mtDNA being higher than 650 copies/µL showed moderate predictive power (AUROC 0.71 (0.53–071)) for the identification of postoperative atrial fibrillation. In conclusion, plasma levels of mtDNA were lower in patients undergoing cardiac surgery with MiECC compared to cCPB. The amount of mtDNA at the beginning of the CPB was associated with postoperative atrial fibrillation independent of the type of cardiopulmonary bypass.

The role of mtDAMPs in the trauma-induced systemic inflammatory response syndrome

“…The plasma mtDNA level of patients undergoing MiECC is lower than that during CPB surgery and is positively correlated with postoperative myocardial injury (94). MtDAMPs such as TFAM and cytochrome c elevated in venous grafts after CABG surgery (95).…”

“…MaxiK expression was significantly increased in the cerebral cortex, which may activate NLRP3 inflammasome by promoting K + transport (94). STING/NLRP3 signaling pathway was involved in neuroinflammation after TBI (101).…”

“…The elevated plasma mtDNA level during cardiopulmonary bypass (CPB) surgery may be involved in SIRS pathogenesis and the related postoperative inflammatory events (such as postoperative atrial fibrillation and infection) (67). Compared with traditional CPB, minimally invasive extracorporeal circulation (MiECC) results in a lower plasma mtDNA level, positively correlated with CPB duration and postoperative myocardial injury (94). Naase et al further confirmed that mtDNA-mediated inflammation through TLR9 and TLR9 antagonist administration significantly reduced IL-6 expression (122).…”