title: Right ventricular failure secondary to chronic overload in congenital heart disease: an experimental model for therapeutic innovation.
abstract: OBJECTIVE
  Mortality and morbidity related to right ventricular failure remain a problem for the long-term outcome of congenital heart diseases. Therapeutic innovation requires establishing an animal model reproducing right ventricular dysfunction secondary to chronic pressure-volume overload.
  
  
  METHODS
  Right ventricular tract enlargement by transvalvular patch and pulmonary artery banding were created in 2-month-old piglets (n = 6) to mimic repaired tetralogy of Fallot. Age-matched piglets were used as controls (n = 5). Right ventricular function was evaluated at baseline and 3 and 4 months of follow-up by hemodynamic parameters and electrocardiography. Right ventricular tissue remodeling was characterized using cellular electrophysiologic and histologic analyses.
  
  
  RESULTS
  Four months after surgery, right ventricular peak pressure increased to 75% of systemic pressure and pulmonary regurgitation significantly progressed, end-systolic and end-diastolic volumes significantly increased, and efficient ejection fraction significantly decreased compared with controls. At 3 months, the slope of the end-systolic pressure-volume relationship was significantly elevated compared with baseline and controls; a significant rightward shift of the slope, returning to the baseline value, was observed at 4 months, whereas stroke work progressed at each step and was significantly higher than in controls. Four months after surgery, QRS duration was significantly prolonged as action potential duration. Significant fibrosis and myocyte hypertrophy without myolysis and inflammation were observed in the operated group at 4 months.
  
  
  CONCLUSIONS
  Various aspects of early right ventricular remodeling were analyzed in this model. This model reproduced evolving right ventricular alterations secondary to chronic volumetric and barometric overload, as observed in repaired tetralogy of Fallot with usual sequelae, and can be used for therapeutic innovation.
authors.affiliation: Département de Recherche Médicale, CNRS UMR 8162, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. v.lambert@ccml.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Lambert
authors.forename: André
authors.initials: A
authors.lastname: Capderou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Le Bret
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
authors.forename: Edith
authors.initials: E
authors.lastname: Deroubaix
authors.forename: Elodie
authors.initials: E
authors.lastname: Gouadon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Raymond
authors.forename: Bertrand
authors.initials: B
authors.lastname: Stos
authors.forename: Alain
authors.initials: A
authors.lastname: Serraf
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Renaud
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005355:Fibrosis; D006329:Heart Conduction System / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006439:Hemodynamics; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D015203:Reproducibility of Results; D013318:Stroke Volume; D013552:Swine; D013771:Tetralogy of Fallot / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D016278:Ventricular Function, Right; D017725:Ventricular Pressure; D020257:Ventricular Remodeling