Exploring the failing right ventricle in pulmonary hypertension by cardiac magnetic resonance: An in vivo study utilizing Macitentan

Figures

• 

  Figure 1. Effect of 3‐week Maci or Veh treatment on Su/Hx‐induced PAH determined by terminal hemodynamic measurements and postmortem histology of CMR rats. (a) RVSP, (b) RV hypertrophy, (c) representative micrograph of Control Veh, Su/Hx Veh, and Su/Hx Maci, (d) % remodeled vessels, and (e) BNP plasma levels assessed by ELISA. Data represented as mean ± standard error of the mean. n = 4 for RVSP, RV hypertrophy, and BNP ELISA, n = 6 for % remodeled vessels, *p < 0.05, **p < 0.01, ***p < 0.001 as indicated, determined by one‐way analysis of variance with Tukey's post hoc analysis, scale bar in each micrograph = 50 µm. BNP, brain natriuretic peptide; CMR, cardiac magnetic resonance; ELISA, enzyme‐linked immunosorbent assay; Maci, Macitentan; PAH, pulmonary arterial hypertension; RV, right ventricle; RVSP, RV systolic pressure; Veh, vehicle.

• 

  Figure 2. Representative CMR short axis cine images taken at diastole of baseline, and 2 and 3‐week CMRs treated with either Maci or Veh. Su/Hx rats with Macitentan (a), Su/Hx vehicle, (b) and Control vehicle (c). LV and RV identified. Short axis cine images were acquired using a slice thickness of 1.5mm ensuring that the entirety of the biventricular length was covered. CMR, cardiac magnetic resonance; LV, left ventricle; Maci, Macitentan; RV, right ventricle; Veh, vehicle.

• 

  Figure 3. Repeat CMR analysis of the effect of Maci or Veh on RVEF and RV hypertrophy (RV/LV+ S) across 3‐week treatment. Su/Hx with Macitentan (a) RVEF and (b) RV hypertrophy. Su/Hx vehicle (c) RVEF and (d) RV hypertrophy. Control vehicle (e) RVEF and (f) RV hypertrophy. Data represented as mean ± standard error of the mean. n = 5–6, *p < 0.05, **p < 0.01, as indicated, determined by repeated measures one‐way analysis of variance or mixed effects model with Tukey's post hoc analysis. CMR, cardiac magnetic resonance; LV, left ventricle; Maci, Macitentan; RV, right ventricle; RVEF, RV ejection fraction; Veh, vehicle.

• 

  Figure 4. Repeat CMR analysis of the effect of Maci or Veh on RV and LV plus septum mass indexed to TBSA (cm2). Su/Hx with Maci (a) RV mass index and (b) LV + S mass index. Su/Hx vehicle (c) RV mass and (d) Su/Hx vehicle LV + S mass index. Control vehicle (e) RV mass index and (f) LV + S mass index. Data represented as mean ± standard error of the mean. n = 5–6, *p < 0.05, **p < 0.001 as indicated, determined by repeated measures one‐way analysis of variance or mixed effects model with Tukey's post hoc analysis. CMR, cardiac magnetic resonance; LV, left ventricle; Maci, Macitentan; RV, right ventricle; RVEF, RV ejection fraction; Veh, vehicle; TBSA, total body surface area.

• 

  Figure 5. Repeat CMR analysis of the effect of Maci or Veh on RVESVi and RVEDVi across 3‐week treatment, volumes are indexed to TBSA (cm2). Su/Hx with Maci (a) RVESVi and (b) RVEDVi. Su/Hx vehicle (c) RVESVi and (d) RVEDVi. Control vehicle (e) RVESVi and (f) RVEDVi. Data represented as mean± standard error of the mean. n = 5–6, *p < 0.05, **p < 0.01, ***p < 0.001 as indicated, determined by repeated measures one‐way analysis of variance or mixed effects model with Tukey's post hoc analysis. CMR, cardiac magnetic resonance; Maci, Macitentan; RVEDVi, right ventricular end‐diastolic volume index; RVESVi, right ventricular end‐systolic volume index; Veh, vehicle; TBSA, total body surface area.

• 

  Figure 6. Repeat CMR analysis of the effect of Maci or Veh on LVEI. Su/Hx with Macitentan (a) systole LVEI and (b) diastole LVEI. Su/Hx vehicle (c) systole LVEI and (d) diastole LVEI. Control vehicle (e) systole LVEI, (f) diastole LVEI. Data represented as mean ± standard error of the mean. n = 5–6, *p < 0.05, **p < 0.01 as indicated, determined by repeated measures one‐way analysis of variance or mixed effects model with Tukey's post hoc analysis. CMR, cardiac magnetic resonance; LVEI, left ventricular eccentricity index; Maci, Macitentan; Veh, vehicle.