Maintained right ventricular pressure overload induces ventricular-arterial decoupling in mice.

What is the central question of this study? The aim was to investigate whether complementary assessment of non-invasive ultrasound imaging together with closed chest-derived intracardiac pressure-volume catheterization is applicable to mice for an in-depth characterization of right ventricular (RV) function even upon maintained pressure overload. What is the main finding and its importance? Characterization of RV function by the complementary use of echocardiographic imaging together with pressure-volume catheterization reveals ventricular-arterial decoupling upon maintained pressure overload, where RV systolic function correlates with ventricular-arterial coupling rather than contractility, whereas diastolic function correlates well with RV diastolic pressure. This combined approach allows us to phenotype RV function and dysfunction better in genetically modified and/or pharmacologically treated mice. Assessment of right ventricular (RV) function in rodents is a challenge because of the complex RV anatomy and structure. To date, the best characterization of RV function has been achieved by accurate cardiovascular phenotyping, involving a combination of non-invasive imaging and intracardiac pressure-volume measurements. We sought to investigate the feasibility of two complementary phenotyping techniques for the evaluation of RV function in an experimental mouse model of sustained RV pressure overload. Mice underwent either sham surgery (n = 5) or pulmonary artery banding (n = 8) to induce isolated RV pressure overload. After 3 weeks, indices of RV function were assessed by echocardiography (Vevo2100) and closed chest-derived invasive pressure-volume measurements (PVR-1030). Pulmonary artery banding resulted in RV hypertrophy and dilatation accompanied by systolic and diastolic dysfunction. Invasive RV haemodynamic measurements demonstrated an increased end-systolic elastance and arterial elastance after pulmonary artery banding compared with sham operation, resulting in ventricular-arterial decoupling. Regression analysis revealed that tricuspid annular plane systolic excursion is correlated with ventricular-arterial coupling (r² = 0.77, P = 0.002) rather than with RV contractility (r² = -0.61, P = 0.07). Furthermore, the isovolumic relaxation time to ECG-derived R-R interval and the ratio of the early diastolic peak velocity measured by pulsed wave Doppler to the early diastolic peak obtained during tissue Doppler imaging correlate well with RV end-diastolic pressure (r² = 0.87, P = 0.0001 and r² = 0.82, P = 0.0009, respectively). Commonly used indices of systolic RV function are associated with RV-arterial coupling rather than contractility, whereas diastolic indices well correlate with end-diastolic pressure when there is maintained pressure overload.

Boehm M ，Lawrie A ，Wilhelm J ，Ghofrani HA ，Grimminger F ，Weissmann N ，Seeger W ，Schermuly RT ，Kojonazarov B ... -  《-》

Pressure Overload Creates Right Ventricular Diastolic Dysfunction in a Mouse Model: Assessment by Echocardiography.

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. 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. 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). 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.

Egemnazarov B ，Schmidt A ，Crnkovic S ，Sydykov A ，Nagy BM ，Kovacs G ，Weissmann N ，Olschewski H ，Olschewski A ，Kwapiszewska G ，Marsh LM ... -  《-》

Myocardial tissue Doppler-based indexes to distinguish right ventricular volume overload from right ventricular pressure overload.

Hsiao SH ，Wang WC ，Yang SH ，Lee CY ，Chang SM ，Lin SK ，Chiou KR ... -  《-》

Influence of right ventricular pressure and volume overload on right and left ventricular diastolic function.

Ventricular interdependence may account for altered ventricular mechanics in congenital heart disease. The present study aimed to identify differences in load-dependent right ventricular (RV)-left ventricular (LV) interactions in porcine models of pulmonary stenosis (PS) and pulmonary insufficiency (PI) by invasive admittance-derived hemodynamics in conjunction with noninvasive cardiovascular magnetic resonance (CMR). Seventeen pigs were used in the study (7 with PS, 7 with PI, and 3 controls). Progressive PS was created by tightening a Teflon tape around the pulmonary artery, and PI was created by excising 2 leaflets of the pulmonary valve. Admittance catheterization data were obtained for the RV and LV at 10 to 12 weeks after model creation, with the animal ventilated under temporary diaphragm paralysis. CMR was performed in all animals immediately prior to pressure-volume catheterization. In the PS group, RV contractility was increased, manifested by increased end-systolic elastance (mean difference, 1.29 mm Hg/mL; 95% confidence interval [CI], 0.57-2.00 mm Hg/mL). However, in the PI group, no significant changes were observed in RV systolic function despite significant changes in RV diastolic function. In the PS group, LV end-systolic volume was significantly lower compared with controls (mean difference, 25.1 mL; 95% CI, -40.5 to -90.7 mL), whereas in the PI group, the LV showed diastolic dysfunction, demonstrated by an elevated isovolumic relaxation constant and ventricular stiffness (mean difference, 0.03 mL-1; 95% CI, -0.02 to 0.09 mL-1). The LV exhibits systolic dysfunction and noncompliance with PI. PS is associated with preserved LV systolic function and evidence of some LV diastolic dysfunction. Interventricular interactions influence LV filling and likely account for differential effects of RV pressure and volume overload on LV function.

Jani V ，Konecny F ，Shelby A ，Kulkarni A ，Hammel J ，Schuster A ，Lof J ，Right Heart Research Group ，Danford D ，Kutty S ... -  《-》

Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension.

Tello K ，Wan J ，Dalmer A ，Vanderpool R ，Ghofrani HA ，Naeije R ，Roller F ，Mohajerani E ，Seeger W ，Herberg U ，Sommer N ，Gall H ，Richter MJ ... -  《-》