title: Pressure Overload Creates Right Ventricular Diastolic Dysfunction in a Mouse Model: Assessment by Echocardiography.
abstract: BACKGROUND
  Noninvasive diagnostic tools for right ventricular (RV) dysfunction measurements are increasingly being used, although their association with the pathologic mechanisms of dysfunction is poorly understood. Although investigations have focused mainly on RV systolic function, RV diastolic function remains mostly neglected. The aim of this study was to test which echocardiographic parameters best reflect RV diastolic function in mice.
  
  
  METHODS
  Pulmonary artery banding (PAB) was used to induce RV pressure overload in mice. Transthoracic echocardiography and invasive hemodynamic measurements were performed after 3 weeks in PAB and sham-operated mice. Subsequently, the hearts were investigated by histology and analyzed for gene expression.
  
  
  RESULTS
  PAB-induced pressure overload (RV systolic pressure PAB 52.6 ± 11.8 mm Hg vs sham 27.0 ± 2.7 mm Hg) resulted in RV hypertrophy and remodeling, as reflected by increased Fulton index (PAB 0.37 ± 0.05 vs sham 0.25 ± 0.02, P = .001). Masson's trichrome staining revealed increased interstitial fibrosis (PAB 12.25 ± 3.12% vs sham 3.97 ± 1.58%, P = .002). This was associated with significant systolic RV dysfunction as demonstrated by reduced contractility index and diastolic dysfunction as demonstrated by end-diastolic pressure (PAB 2.66 ± 0.83 mm Hg vs sham 1.49 ± 0.50 mm Hg, P < .001) and τ (PAB 40.0 ± 16.1 msec vs sham 13.0 ± 3.5 msec, P < .001). Messenger ribonucleic acid expression of β-myosin heavy chain, atrial and brain natriuretic peptides, collagen family members was elevated, and the sarco/endoplasmic reticulum Ca(2+)-ATPase was decreased. Echocardiography revealed significant increases in RV free wall thickness and isovolumic relaxation time and a decrease in left ventricular eccentricity index, E', and tricuspid annular plane systolic excursion. Isovolumic relaxation time and E' were significantly correlated with end-diastolic pressure (rs = 0.511 and -0.451) and τ (rs = 0.739 and -0.445, respectively). Moreover, E' was negatively correlated with the degree of RV fibrosis (rs = -0.717).
  
  
  CONCLUSIONS
  Within 3 weeks, PAB causes pressure overload-induced RV hypertrophy and remodeling with compensated systolic and diastolic dysfunction in mice. RV free wall thickness, tricuspid annular plane systolic excursion, E', E/E' ratio, and isovolumic relaxation time appear to be the most reliable echocardiographic parameters for the assessment of RV dysfunction.
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria. Electronic address: bakytbek.egemnazarov@lvr.lbg.ac.at.
authors.forename: Bakytbek
authors.initials: B
authors.lastname: Egemnazarov
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
authors.forename: Slaven
authors.initials: S
authors.lastname: Crnkovic
authors.affiliation: University of Giessen and Marburg Lung Center, Excellence Cluster Cardio-Pulmonary System, Giessen, Germany.
authors.forename: Akylbek
authors.initials: A
authors.lastname: Sydykov
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Bence M
authors.initials: BM
authors.lastname: Nagy
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gabor
authors.initials: G
authors.lastname: Kovacs
authors.affiliation: University of Giessen and Marburg Lung Center, Excellence Cluster Cardio-Pulmonary System, Giessen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Horst
authors.initials: H
authors.lastname: Olschewski
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Experimental Anesthesiology, Department of Anesthesia and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Olschewski
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Experimental Anesthesiology, Department of Anesthesia and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kwapiszewska
authors.affiliation: Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
authors.forename: Leigh M
authors.initials: LM
authors.lastname: Marsh
mesh_terms: D000818:Animals; D003971:Diastole; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods*; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016278:Ventricular Function, Right / Q000502:physiology*; D017725:Ventricular Pressure / Q000502:physiology*
keywords: Diastolic dysfunction; Dysfunction; Echocardiography; Fibrosis; Pressure overload; Right ventricle