Abstract 16125: Persistent Atrial Fibrillation is Associated with Selective Reduction in Rotenone-Sensitive NADH Oxidoreductase Activity in Human Atria
Introduction: Atrial fibrillation (AF) causes electrical and structural alterations that promote the substrate for AF recurrence and progression. Although remodeling of the atria has been well characterized, the metabolic basis for such alterations in human atria that contribute to the progression of the AF substrate has not been fully defined. Since mitochondria play an essential role in maintaining cardiac energetics, oxidant production and regulation of cell death/survival, AF-associated mitochondrial electron transport chain (ETC) dysfunction could contribute to progression of AF. The aim of this study was to determine differences in activity of mitochondrial respiratory chain complexes in nonfailing atria from patients with and without AF.
Methods: Freshly removed right atrial appendage tissue from patients with (AF, n=8) and without AF (nAF, n=10) undergoing cardiac bypass surgery who also had well-preserved LV function were immediately frozen in liquid nitrogen and stored at -80 ºC. Enzymatic activities of mitochondrial ETC complexes were assayed in homogenates with a Clark oxygen electrode and normalized to the citrate synthase (CS) activity. Relative activities of complexes were expressed as ngatom O2/min/CS activity.
Results: Patients with AF were older, but there were no significant differences in the proportion that were male or had previous myocardial infarction, diabetes, hyperlipidemia or hypertension. There were no significant differences in LV ejection fraction, LV mass index, left atrial volume index or use of medications such as aspirin, ACE inhibitors or β-blockers. Compared to nAF patients, AF patients had significantly reduced rotenone-sensitive NADH oxidoreductase activity (Complex I: 11 ± 1 vs. 19 ± 1, p=0.007). Trends of declining succinate dehydrogenase (Complex II: 14 ± 1 vs. 15 ± 0.7, p=0.41) and cytochrome c oxidoreductase (Complex IV: 45 ± 3 vs. 48 ± 2, p=0.45) activities were observed in patients with AF as compared to nAF patients; however, this did not reach statistical significance.
Conclusion: Selective impairment of atrial mitochondrial ETC activity in patients with AF could compromise cardiac energetic reserves and contribute to the evolution of the functional substrate promoting progression of AF.
- © 2012 by American Heart Association, Inc.