title: Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability.
abstract: The failing ventricular myocardium is characterized by reduction of high-energy phosphates and reduced activity of the phosphotransfer enzymes creatine kinase (CK) and adenylate kinase (AK), which are responsible for transfer of high-energy phosphoryls from sites of production to sites of utilization, thereby compromising excitation-contraction coupling. In humans with chronic atrial fibrillation (AF) unassociated with congestive heart failure (CHF), impairment of atrial myofibrillar energetics linked to oxidative modification of myofibrillar CK has been observed. However, the bioenergetic status of the failing atrial myocardium and its potential contribution to atrial electrical instability in CHF have not been determined. Dogs with (n = 6) and without (n = 6) rapid pacing-induced CHF underwent echocardiography (conscious) and electrophysiological (under anesthesia) studies. CHF dogs had more pronounced mitral regurgitation, higher atrial pressure, larger atrial area, and increased atrial fibrosis. An enhanced propensity to sustain AF was observed in CHF, despite significant increases in atrial effective refractory period and wavelength. Profound deficits in atrial bioenergetics were present with reduced activities of the phosphotransfer enzymes CK and AK, depletion of high-energy phosphates (ATP and creatine phosphate), and reduction of cellular energetic potential (ATP-to-ADP and creatine phosphate-to-Cr ratios). AF duration correlated with left atrial area (r = 0.73, P = 0.01) and inversely with atrial ATP concentration (r = -0.75, P = 0.005), CK activity (r = -0.57, P = 0.054), and AK activity (r = -0.64, P = 0.02). Atrial levels of malondialdehyde, a marker of oxidative stress, were significantly increased in CHF. Myocardial bioenergetic deficits are a conserved feature of dysfunctional atrial and ventricular myocardium in CHF and may constitute a component of the substrate for AF in CHF.
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Cha
authors.forename: Petras P
authors.initials: PP
authors.lastname: Dzeja
authors.forename: Win K
authors.initials: WK
authors.lastname: Shen
authors.forename: Arshad
authors.initials: A
authors.lastname: Jahangir
authors.forename: Chari Y T
authors.initials: CY
authors.lastname: Hart
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001281:Atrial Fibrillation; D002304:Cardiac Pacing, Artificial; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D004452:Echocardiography; D004594:Electrophysiology; D004734:Energy Metabolism; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D010725:Phosphocreatine; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase