Macitentan treatment improves the dysfunctional right ventricle in a sugen/hypoxic rat model of pulmonary hypertension

Background: Macitentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). Using cardiac magnetic resonance imaging (CMR), which is the gold standard for assessing ventricular mass, volumes and function, we wished to examine the effect of Macitentan therapy on the right ventricle (RV) in the Sugen 5416 combined with chronic hypoxia (Su/Hx) model of PAH. Methods: 4-week old Sprague Dawley rats received a subcutaneous injection of Sugen 5416 [20mg/kg], followed by 3 weeks hypobaric hypoxia (550mmHg), then two weeks in normoxic conditions. Rats subsequently received either Macitentan (30mg/kg) or vehicle (gelatin) via daily oral gavage for a further three weeks. CMR’s, using a Bruker Pharmascan 7T system, were taken at week 5, before treatment commenced (baseline), and at week 7 and 8. Planimetry determined RV end diastolic and systolic volumes (RVEDV, RVESV), RV and LV ejection fractions (RVEF, LVEF) and RV and LV masses. Results: Macitentan therapy in Su/Hx rats led to an improvement in both RVEF (30.6% vs 44.1% vs 47.8% p Conclusion: Macitentan treatment resulted in improved RV function and structure by increasing RVEF and lowering RV hypertrophy in a Su/Hx rat model of PAH. Further research is needed to confirm if Macitentan is having a direct effect on the RV, or if improvements to RV function are confounded by changes in the pulmonary vasculature.