Use of monoamine oxidase and redox enzymes in atrial tissue as novel predictors of postoperative atrial fibrillation

Abstract

Postoperative atrial fibrillation (POAF) occurs in approximately 30% of cardiac surgery patients. The complication occurs despite advances in surgical procedures. It is associated with increased mortality, morbidity, and healthcare cost. The exact pathogenesis of this complication is unknown, but oxidative stress and inflammation are considered to be significant factors. A precisely controlled balance between reactive oxygen species (ROS) generation and ROS scavenging influence the oxidative environment within cells and tissues. Increased activity of monoamine oxidase (MAO) activity, a ROS generating enzyme, can produce a more oxidative environment. A decrease in glutathione (GSH), a ROS scavenging molecule, can also yield an oxidative environment. The enzymes GSH-peroxidase (GPx) and GSH-reductase (GR) are responsible for maintaining the cellular redox environment within a range that is compatible with favorable homeostasis. Despite the well-characterized role that these enzymes play in maintaining redox environment, a comprehensive evaluation of these enzymes in human myocardium has never been attempted. Furthermore, since reports have recently documented the association between oxidative stress in atrial tissue and the incidence of POAF, we tested the hypothesis that these enzymes are associated with POAF, in a cohort of patients undergoing cardiac surgery at Vidant Medical Center, East Carolina Heart Institute (ECHI). Human right atrial appendage tissue were obtained from 244 patients undergoing elective coronary artery bypass graft surgery at ECHI between January, 2010, and December, 2012. The generation of ROS were determined using assays on MAO, NADPH oxidase (NOX), along with the activity of glutathione reductase (GR) and glutathione peroxidase (GPx). Patient outcomes, including POAF development, were analyzed in relation to the assays performed. A statistical model was then created to measure the association for risk of POAF development. This was the first study to determine that MAO activity is a major source of ROS in human atrial tissue. MAO activity is significantly associated with POAF. Total glutathione (GSHt) activity is inversely related to POAF development. GPx is also significantly associated with POAF as well, but the trend is not a linear. GR activity is not correlated with POAF. MAO, GSHt and GPx are enzymes that contribute to the atrial oxidative environment and increased risk of POAF development. Because this is a pilot study, further exploration is needed to validate our study and to determine if and where these enzymes fit in the etiology of POAF.