title: Left ventricular systolic dysfunction induced by ventricular ectopy: a novel model for premature ventricular contraction-induced cardiomyopathy.
abstract: BACKGROUND
  Premature ventricular contractions (PVCs) commonly coexist with cardiomyopathy. Recently, PVCs have been identified as a possible cause of cardiomyopathy. We developed a PVC-induced cardiomyopathy animal model using a novel premature pacing algorithm to assess timeframe and reversibility of this cardiomyopathy and examine the associated histopathologic abnormalities.
  
  
  RESULTS
  Thirteen mongrel dogs were implanted with a specially programmed pacemaker capable of simulating ventricular extrasystoles. Animals were randomly assigned to either 12 weeks of bigeminal PVCs (n = 7) or no PVCs (control, n = 6). Continuous 24-hour Holter monitoring corroborated ventricular bigeminy in the PVC group (PVC, 49.8% versus control, < 0.01%; P<0.0001). After 12 weeks, only the PVC group had cardiomyopathy, with a significant reduction in left ventricular ejection fraction (PVC, 39.7 ± 5.4% versus control, 60.7 ± 3.8%; P < 0.0001) and an increase in left ventricular end-systolic dimension (PVC, 33.3 ± 3.5 mm versus control, 23.7 ± 3.6 mm; P < 0.001). Ventricular effective refractory period showed a trend to prolong in the PVC group. PVC-induced cardiomyopathy was resolved within 2 to 4 weeks after discontinuation of PVCs. No inflammation, fibrosis, or changes in apoptosis and mitochondrial oxidative phosphorylation were observed with PVC-induced cardiomyopathy.
  
  
  CONCLUSIONS
  This novel PVC animal model demonstrates that frequent PVCs alone can induce a reversible form of cardiomyopathy in otherwise structurally normal hearts. PVC-induced cardiomyopathy lacks gross histopathologic and mitochondrial abnormalities seen in other canine models of cardiomyopathy.
authors.affiliation: McGuire VA Medical Center, Cardiology Division, and Virginia Commonwealth University, Richmond, VA, USA. jose.huizar2@va.gov
authors.forename: Jose F
authors.initials: JF
authors.lastname: Huizar
authors.forename: Karoly
authors.initials: K
authors.lastname: Kaszala
authors.forename: Jonathan
authors.initials: J
authors.lastname: Potfay
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Minisi
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lesnefsky
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Kukreja
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Hoke
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Thacker
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ellenbogen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wood
mesh_terms: D000465:Algorithms; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D008929:Mitochondria, Heart / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D010085:Oxidative Phosphorylation; D010138:Pacemaker, Artificial; D013318:Stroke Volume / Q000502:physiology; D013599:Systole / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000503:physiopathology*; D018879:Ventricular Premature Complexes / Q000150:complications* / Q000503:physiopathology*