title: Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model.
abstract: In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca(2+)-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism.
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; Centro Nacional de Investigaciones Cardiovasculares Carlos III-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain; jaimeaguero30@hotmail.com.
authors.forename: Jaume
authors.initials: J
authors.lastname: Aguero
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Lahouaria
authors.initials: L
authors.lastname: Hadri
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Carlos
authors.initials: C
authors.lastname: Santos-Gallego
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fish
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Nadjib
authors.initials: N
authors.lastname: Hammoudi
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaanine
authors.affiliation: Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Samantha
authors.initials: S
authors.lastname: Torquato
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Charbel
authors.initials: C
authors.lastname: Naim
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain;
authors.forename: Borja
authors.initials: B
authors.lastname: Ibanez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain;
authors.forename: Daniel
authors.initials: D
authors.lastname: Pereda
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain;
authors.forename: Ana
authors.initials: A
authors.lastname: García-Alvarez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Partho P
authors.initials: PP
authors.lastname: Sengupta
authors.affiliation: Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Leopold
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress; D005355:Fibrosis / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009200:Myocardial Contraction; D011651:Pulmonary Artery / Q000473:pathology* / Q000503:physiopathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020257:Ventricular Remodeling
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: SERCA2a; aldosterone; echocardiography; pressure-volume relationships; pulmonary hypertension model; right ventricular remodeling