title: Right ventricular plasticity in a porcine model of chronic pressure overload.
abstract: BACKGROUND
  Ventricular-arterial coupling is a measure of the relationship between ventricular contractility and afterload. We sought to determine the relationship between ventricular-arterial coupling and right ventricular (RV) remodeling in a novel porcine model of progressive pulmonary hypertension (PH).
  
  
  METHODS
  Chronic PH was induced in pigs by ligation of the left pulmonary artery (PA) followed by 5 weekly injections of cyanoacrylate to progressively obstruct the right lower lobe arteries (PH group, n = 10). At 6 weeks, 5 PH animals underwent reperfusion of the left lung through conduit anastomosis to decrease RV afterload, whereas 5 other animals received no treatment. Five sham-operated piglets were used as controls. RV function was assessed using echocardiography and conductance catheterization. RV gene expression of beta-myosin heavy chain (β-MHC) and B-type natriuretic peptide (BNP) were quantified by polymerase chain reaction.
  
  
  RESULTS
  At 6 weeks, compared with controls, the PH group had higher mean PA pressure (32 ± 6 vs 14 ± 2 mm Hg, p < 0.01). The increase in RV elastance was insufficient to compensate for the increase in pulmonary arterial elastance in the PH group and altered ventricular-arterial coupling occurred (0.65 ± 0.16 vs 1.28 ± 0.14, p < 0.01). The degree of ventricular-arterial uncoupling was related to RV enlargement and systolic dysfunction. Ventricular-arterial uncoupling and increased RV mass index were associated with up-regulation of β-MHC and BNP expression.
  
  
  CONCLUSIONS
  Ventricular-arterial coupling is closely associated with ventricular remodeling and systolic function as well as contractile and BNP gene expression. Dynamic changes in myosin expression may determine RV work efficiency in PH.
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France. Electronic address: julien.guihaire@u-psud.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Guihaire
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Palo Alto, California.
authors.forename: François
authors.initials: F
authors.lastname: Haddad
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: David
authors.initials: D
authors.lastname: Boulate
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: André
authors.initials: A
authors.lastname: Capderou
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Decante
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital of Rennes, Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Flécher
authors.affiliation: Faculté de médecine, Kremlin-Bicêtre, AP-HP, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, INSERM U999, Marie Lannelongue Hospital, University of Paris-Sud, Le Plessis Robinson, France.
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.affiliation: Faculté de médecine, Kremlin-Bicêtre, AP-HP, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, INSERM U999, Marie Lannelongue Hospital, University of Paris-Sud, Le Plessis Robinson, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hervé
authors.affiliation: Faculté de médecine, Kremlin-Bicêtre, AP-HP, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, INSERM U999, Marie Lannelongue Hospital, University of Paris-Sud, Le Plessis Robinson, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital of Rennes, Rennes, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Verhoye
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dartevelle
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.affiliation: Laboratory of Surgical Research and INSERM U999, University of Paris-Sud, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003487:Cyanoacrylates / Q000009:adverse effects / Q000378:metabolism; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D011651:Pulmonary Artery / Q000503:physiopathology*; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers; D003487:Cyanoacrylates; D020097:Natriuretic Peptide, Brain; D018995:Myosin Heavy Chains
keywords: animal model; pulmonary hypertension; right ventricle; ventricular–arterial coupling