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Publication Date

10-29-2018

Keywords

atrial fibrillation, metabolites, mechanisms, right atrium, left atrium, biomarkers

Abstract

Background: Several studies have demonstrated genomic, morphological, and electrophysiological differences between the right atrium and left atrium, suggesting that dissimilar mechanisms may contribute to the development and progression of atrial fibrillation (AF). Therefore, differences in metabolic response to AF between atria are foreseeable. Given the complexity of AF development and progression, understanding AF-associated changes in metabolites in both atria will help in better clinical management of AF.

Purpose: To compare potential changes in metabolites in the right atrial (RAA) and left atrial (LAA) appendage tissue from patients with (AF+) and without (non-AF) history of AF.

Methods: RAA and LAA tissue from AF+ (n = 20) and non-AF (n = 20) patients undergoing elective open heart surgery at Aurora St. Luke’s Medical Center (Milwaukee, WI) was collected. The tissue was snap-frozen in liquid nitrogen and stored at -80°C. Metabolites were profiled in frozen tissue using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS). Comparison between groups was done using the 2 sample t-test and Wilcoxon rank-sum test, with 5% level of significance. The study was approved by the local institutional review board.

Results: A total of 24 metabolites related to glycolysis and tricarboxylic acid cycle (TCA) were identified. The most significant AF-associated changes in metabolites were observed in RAA compared to LAA tissue. In AF+ patients, glycolysis metabolites’ level of glucose-6-phosphate (P = 0.03) and phosphoenolpyruvate (P = 0.03) was significantly reduced in RAA, while 2-phosphoglycerate (P = 0.02) level was reduced in LAA. AF+ was associated with a significant decrease in TCA metabolites, including NAD+ (P = 0.03), GDP (P = 0.05), and citrate (P = 0.03), in RAA without considerable changes of metabolites in LAA. In addition, there was AF-associated decrease in the total pool of adenine nucleotides (ie, AMP + ADP + ATP, P = 0.02) and glutathione level (P = 0.03) in RAA when compared to LAA.

Conclusion: Atrial fibrillation is associated with different metabolic profiles between right and left atria. This may reflect different metabolic mechanisms underlying right and left atrial involvement in AF patients and may help to reveal potential chamber-specific biomarkers and targets for better preventive strategies and development of novel cardioprotective interventions.

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