Wang Yi-Dan, Li Yi-Dan, Ding Xue-Yan, Wu Xiao-Peng, Li Cheng, Guo Di-Chen, Shi Yan-Ping, Lu Xiu-Zhang
Department of Echocardiography, Heart Center, Beijing Chao Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China.
Beijing Key Laboratory of Hypertension, Beijing, 100020, China.
Int J Cardiovasc Imaging. 2019 Mar;35(3):441-450. doi: 10.1007/s10554-018-1468-0. Epub 2018 Oct 22.
Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17β-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLS) and RV longitudinal shortening fraction (RVLSF) were also used to quantify RV function. RV morphology was determined by echocardiographic and histological analysis. TAPSE, RVFAC and s' were reduced, and RIMP was elevated in the MCT-treated group and vehicle-treated group, when compared with control group (P < 0.01). TAPSE, RVFAC and s' in the E2 group were higher, while RIMP was lower than those in the MCT-treated group and vehicle-treated group (P < 0.01). Myocardial functional parameters (RVLS and RVLSF) were also higher in the E2 group. Enhanced serum E2 levels were closely correlated with the improvement in RV functional parameters and enhancement of serum BNP levels (P < 0.01 for all groups). RV function decreased significantly in male rats with MCT-induced PAH, while E2 exhibited a protective effect on RV function, suggesting that E2 is a critical modulator of sex differences in PAH.
肺动脉高压(PAH)在女性中更为常见。矛盾的是,女性患者的右心室(RV)功能比男性更好,生存率也更高。然而,17β-雌二醇(E2)对PAH患者右心室功能的影响尚未得到研究。将24只雄性大鼠暴露于野百合碱(MCT)以诱导实验性PAH,同时分别用E2或赋形剂进行处理。连同8只对照大鼠在内,在给药4周后对32只大鼠进行超声心动图检查。超声心动图测量右心室功能包括:三尖瓣环平面收缩期位移(TAPSE)、右心室心肌性能指数(RIMP)、右心室面积变化分数(RVFAC)和三尖瓣环收缩速度(s')。右心室游离壁纵向应变(RVLS)和右心室纵向缩短分数(RVLSF)也用于量化右心室功能。通过超声心动图和组织学分析确定右心室形态。与对照组相比,MCT处理组和赋形剂处理组的TAPSE、RVFAC和s'降低,RIMP升高(P < 0.01)。E2组的TAPSE、RVFAC和s'高于MCT处理组和赋形剂处理组,而RIMP低于MCT处理组和赋形剂处理组(P < 0.01)。E2组的心肌功能参数(RVLS和RVLSF)也更高。血清E2水平升高与右心室功能参数的改善和血清BNP水平的升高密切相关(所有组P < 0.01)。MCT诱导的PAH雄性大鼠的右心室功能显著下降,而E2对右心室功能具有保护作用,表明E2是PAH性别差异的关键调节因子。