Characterisation of Plasma Mitochondrial DNA, MMP-9 and Neutrophil Elastase in Patients Undergoing Coronary Artery Bypass Grafting: Effects of Tranexamic Acid and Postoperative Pneumonia

Heart Lung Circ. 2022 Mar;31(3):439-446. doi: 10.1016/j.hlc.2021.08.008. Epub 2021 Oct 7.

Abstract

Background: Postoperative pneumonia is a major cause of morbidity and mortality following cardiac surgery. The inflammatory response to cardiac surgery has been widely studied, but specific mechanisms for postoperative pneumonia have not been determined. Tranexamic acid is renowned for its effect on bleeding but can also modulate inflammatory processes. Cardiac surgery is known to release mitochondrial DAMPs (mtDAMPs) and is linked to postoperative inflammation and atrial fibrillation. We speculated that mtDAMPs might be related to postoperative pneumonia and that this might be modulated by tranexamic acid.

Methods: Forty-one (41) patients from the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial were studied. Levels of mitochondrial DNA, matrix metallopeptidase 9 (MMP-9) and neutrophil elastase (NE) were determined in plasma preoperatively, at 24 and 72 hours post-surgery and correlated with clinical outcome.

Results: mtDNA was significantly elevated postoperatively in the placebo and tranexamic acid (TXA) groups. Neutrophil elastase increased immediately postoperatively and at 24 hours. MMP-9 was elevated in the placebo group early postoperatively and in the TXA group at the immediate postoperative time point and after 24 hours. Six (6) of the 41 (14.6%) patients subsequently developed pneumonia. mtDNA levels were significantly increased at the early postoperative period and the 24-hour time point in patients with pneumonia.

Conclusions: Cardiac surgery releases mtDNA, increases MMP-9 and NE and this was not influenced by TXA. Inflammation postoperatively might be linked to pneumonia since mtDNA was further elevated in these patients. Due to the low number of individuals developing pneumonia, further studies are warranted to clearly identify whether TXA impacts on the inflammatory response in postoperative pneumonia.

Keywords: Mitochondrial DAMPS; Postoperative pneumonia; Tranexamic acid; mtDNA.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antifibrinolytic Agents* / adverse effects
  • Blood Loss, Surgical
  • Coronary Artery Bypass
  • DNA, Mitochondrial / genetics
  • Humans
  • Leukocyte Elastase
  • Matrix Metalloproteinase 9
  • Pneumonia* / etiology
  • Tranexamic Acid* / adverse effects
  • Treatment Outcome

Substances

  • Antifibrinolytic Agents
  • DNA, Mitochondrial
  • Tranexamic Acid
  • Leukocyte Elastase
  • Matrix Metalloproteinase 9