P6 Sex differences in the right ventricle in an experimental model of pulmonary arterial hypertension

Aim There is an unexplained sex paradox in pulmonary arterial hypertension (PAH): PAH occurs 2–4 fold more frequently in women than men; however, compared to men with PAH, women with PAH have better right ventricular (RV) function and survival. Sex differences and the associated mechanism in RV in PAH are not well characterized. This study aimed to characterize sex differences in RV function and structure in PAH. Methods Sprague-Dawley rats were injected with Sugen (25 mg/kg) and exposed to 3 weeks' hypoxia, followed by 5 weeks' normoxia. Control rats received vehicle, followed by 8 weeks' normoxia. RV pressure-volume, hypertrophy, mycyote size, and interstitial and perivascular fibrosis were obtained. Results Sugen-Hypoxia caused significant increases in RV systolic pressure (RVSP), hypertrophy and myocyte size in both sexes. Although Sugen-Hypoxia did not cause significant differences in RVSP and effective arterial elastance (Ea) between sexes, it caused slightly greater increase in RV end-systolic elastance (Ees) in females vs males, leading to a preserved RV-pulmonary artery coupling (Ees/Ea) in females and a significant decrease in Ees/Ea in males. Sugen-Hypoxia caused a significant increase in RV diastolic pressure only in males, associated with significantly higher amount of RV interstitial fibrosis in males vs females. Whilst there were no differences in RV hypertrophy, the female RV had smaller myocytes than males at baseline and the size of the myocytes increased in both sexes after sugen-hypoxia such that myocyte size was the same in male and female Sugen-hypoxic rats. Finally, there was a significant increase in perivascular fibrosis in male Sugen-hypoxic rats only. Conclusions PAH resulted in the same RV afterload in both sexes, but compared to males, RV in females responded differently in both function (RV-pulmonary artery coupling) and structure (myocye size and fibrosis). Future studies on the associated mechanism will provide therapeutic insight for RV in PAH.