Abstract 20004: Aging-Associated Changes in Human Atrial Bioenergetics and Metabolomic Profile Detected by GC/MS and Stable Isotope 18O-assisted Mass Spectrometry
Introduction: Aging-associated alteration in atrial bioenergetics may increase predisposition to electrical and mechanical dysfunction, but has not been fully characterized in human myocardium.
Hypothesis: Simultaneous determination of metabolite level and turnover rates can reveal dynamic metabolic rearrangements in aging human atria.
Methods: Right atrial appendage tissue from 7 aged (mean age 70.1±6.7 yrs) and 7 adult (53.4±4.7 yrs) patients, free of atrial pathology undergoing coronary artery bypass surgery were subjected to metabolite 18O-labeling. Tissue extracts were analyzed using HPLC, GC/MS and stable isotope 18O-assisted mass spectrometry (18O-assisted GC/MS).
Results: PLS DA (Partial Least Square Discriminant Analysis) score plot exhibited distinct clustering of metabolites and 18O-labeling rates between the two age groups (Figure). Selected metabolites of fatty acid, Krebs cycle, glycolysis and nucleotide metabolism, and turnover rates of inorganic phosphate (Pi) (ATP turnover), glucose-6-phosphate (G-6-P) (glycolysis), glucose-1-phosphate (G-1-P) (glycogenolysis) and glycerol-3-phosphate (G-3-P) (mitochondrial substrate shuttle) were differentially altered with aging (Figure). G-6-P and G-3-P turnover rates were higher, while Pi (ATP) turnover and nucleotide (adenosine, AMP) levels were lower in aged human atria.
Conclusions: Thus, metabolomic profiling and 18O-assisted GC/MS analysis of metabolite turnover rates through different metabolic pathways revealed aging-associated dynamic rearrangements in atrial energetic system with potential implications in detecting the effect of aging and aging-associated diseases on atrial structure and function.
- © 2010 by American Heart Association, Inc.