Abstract 2892: Metabolic Profiling Provides Insights Into Right and Left Atrial Profibrillatory Remodeling in Heart Failure
Remodeling of metabolic function has been suggested to contribute to the atrial fibrillation (AF) substrate, but its role has never been studied in defined animal models. Heart failure (HF) leads to atrial structural remodeling and AF susceptibility. This study assessed atrial metabolic remodeling in the HF-induced AF substrate.
Methods: We applied high resolution nuclear magnetic resonance (NMR) spectroscopy to snap-frozen left (LA) and right (RA) atrial tissue from sham (n=7) and ventricular tachypaced (VTP, 240 bpm x 2 wks, n=6) HF dogs. Metabolites were extracted in 6% perchloric acid for NMR analysis.
Results: Of 23 metabolites identified by NMR, 12 were significantly altered (8 in LA and 10 in RA, table⇓). Six metabolites were congruently affected in LA and RA, suggesting a consistent response pattern. Increases in glucose and decreases in α-ketoisovalerate suggest a switch from glycolysis to α-ketoacid metabolism for energy production, with consequences for energy availability and regulation of metabolism. Taurine regulates cell volume, ion transport and contractile function: its accumulation may be detrimental to Ca2+handling and contribute to contractile dysfunction. Increased alanine likely results from enhanced alternate-pathway conversion from pyruvate, due to downregulation of pyruvate dehydrogenase E1 subunit (proteomic analysis: −49% (LA) and −39% (RA), p<0.02), which converts pyruvate to acetyl-CoA. ADP/ATP accumulation in LA suggests more metabolic stress and less effective energy utilization than in RA, consistent with larger LA changes in betaine, glucose, glutamate and NAD/NADH.
Conclusions: Metabolomic analysis reveals both common and distinct responses of the atria to HF, with LA-specific disturbances that may contribute to the primary role of LA in AF maintenance. These responses indicate extensive disruptions in atrial metabolism that likely contribute to atrial remodeling, functional abnormalities and AF promotion in HF.