Substrate modifications precede the development of atrial fibrillation after cardiac surgery: a proteomic study

Atrial fibrillation (AF) is an important cause of morbidity and mortality after cardiac surgery. The pathogenesis of AF appears to be multifactorial but little is known about the cause-effect relationship of substrate modifications with the onset of the arrhythmia. With the use of modern proteomics, this study aims to identify preexisting changes in the left atrium of patients susceptible to postoperative AF.

We analyzed 20 matched patients undergoing elective, first-time coronary artery bypass grafting with no history of AF. They were divided into 2 equal groups according to the development of postoperative AF. Proteomic analysis was performed in left atrial tissue obtained during surgery using two-dimensional difference in gel electrophoresis techniques. Mass spectrometry identified proteins that were differentially expressed in patients who developed AF against those who remained in sinus rhythm.

Proteomic analysis of left atrial tissue identified 19 differentially expressed protein spots between patients who developed postoperative AF and their sinus rhythm counterparts. In patients who developed AF, proteins associated with oxidative stress and apoptosis (peroxiredoxin 1, apoptosis-inducing factor, and 96S protease regulatory subunit 8) as well as acute phase response components (apolipoprotein A-I, fibrinogen) were found to be increased. Conversely, the expression of proteins responsible for glycolysis (enolase) and pyruvate metabolism (pyruvate dehydrogenase) was reduced.

We describe protein changes that precede the development of postoperative AF and which might be suggestive of increased oxidative stress and glycolytic inhibition in the left atrium of patients predilected to AF.