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17?-estradiol preserves right ventricular function in rats with pulmonary arterial hypertension: an echocardiographic and histochemical study.

ABSTRACT: 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 17?-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_FW) 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?FW 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?

SUBMITTER: Wang YD

PROVIDER: S-EPMC6454076 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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17β-estradiol preserves right ventricular function in rats with pulmonary arterial hypertension: an echocardiographic and histochemical study.

Wang Yi-Dan YD Li Yi-Dan YD Ding Xue-Yan XY Wu Xiao-Peng XP Li Cheng C Guo Di-Chen DC Shi Yan-Ping YP Lu Xiu-Zhang XZ

The international journal of cardiovascular imaging 20181022 3

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 d ...[more]

PMID: 30350115

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Project description:BackgroundThe cardioprotective properties of sevoflurane have been reported in studies of the left ventricle. However, whether this volatile anesthetic would also be beneficial for pulmonary vascular remodeling and associated right ventricular hypertrophy (RVH) remained to be explored. Here, we investigated the potential benefit of sevoflurane to right heart function in experimental pulmonary arterial hypertension (PAH).MethodsAdult Wistar rats received one dose peritoneal injection of monocrotaline (MCT, 60 mg/kg) or the equal volume of normal saline. Two weeks later, rats were treated with sevoflurane or sham exposure. PAH status and cardiac function were assessed by echocardiography weekly, and the body weight (BW) was monitored every week. After 6 weeks of exercise, Fulton's index calculation, histological observation, IL-6 and TNF-α immunohistochemical analyses, evaluation of MDA, SOD and GSH-Px levels and NF-κB and MAPK active determination were performed in lung and RV tissue samples.ResultsMCT induced pulmonary vascular remodeling, RVH, increased Fulton's index (P<0.01), and right ventricular failure (RVF) in rats. Animals inhaled sevoflurane had an increased cardiac output (P<0.05) and lower incidence of RVF (P<0.05). Also, these animals had a reduced RVEDD, RVWTd and PAID (P<0.05), increased PV (P<0.05), reduced wall thickness and vascular wall area of pulmonary small vascular (vascular external diameter 50-150 um) (P<0.01), reduced RV fibrosis, and increased RV cardiomyocyte area (P<0.01). Furthermore, sevoflurane reduced IL-6 and TNF-α expression in lungs and heart (P<0.01), decreased level of MDA (P<0.01) and increased activity of SOD and GSH-Px (P<0.01). In addition, it decreased the activities of NF-κB and MAPK pathways (P<0.01).ConclusionSevoflurane reduces pulmonary vascular remodeling and RVH in PAH induced by MCT in rats. This effect is likely due to down-regulation of inflammatory factors IL-6 and TNF-α, reduced level of oxidative stress and the inhibition of NF-κB and MAPK pathways.

Project description:Importance:Current guidelines recommend evaluation for echocardiographically estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg; however, this threshold does not capture all patients at risk. Objectives:To determine if mild echocardiographic pulmonary hypertension (ePH) is associated with reduced right ventricular (RV) function and increased risk of mortality. Design, Setting, and Participants:In this cohort study, electronic health record data of patients who were referred for echocardiography at Vanderbilt University Medical Center, Nashville, Tennessee, from March 1997 to February 2014 and had recorded estimates of RVSP values were studied. Data were analyzed from February 2017 to May 2019. Exposures:Mild ePH was defined as an RVSP value of 33 to 39 mm Hg. Right ventricular function was assessed using tricuspid annular plane systolic excursion (TAPSE), and RV-pulmonary arterial coupling was measured using the ratio of TAPSE to RVSP. Main Outcomes and Measures:Associations of mild ePH with mortality adjusted for relevant covariates were examined using Cox proportional hazard models with restricted cubic splines. Results:Of the 47?784 included patients, 26?758 of 47?771 (56.0%) were female and 6040 of 44?763 (13.5%) were black, and the mean (SD) age was 59 (18) years. Patients with mild ePH had worse RV function compared with those with no ePH (mean [SD] TAPSE, 2.0 [0.6] cm vs 2.2 [0.5] cm; P?<?.001) and nearly double the prevalence of RV dysfunction (32.6% [92 of 282] vs 16.7% [170 of 1015]; P?<?.001). Compared with patients with RVSP less than 33 mm Hg, those with mild ePH also had reduced RV-pulmonary arterial coupling (mean [SD] ratio of TAPSE to RVSP, 0.55 [0.18] mm/mm Hg vs 0.93 [0.39] mm/mm Hg; P?<?.001). An increase in adjusted mortality began at an RVSP value of 27 mm Hg (hazard ratio, 1.32; 95% CI, 1.02-1.70). Female sex was associated with increased mortality risk at any given RVSP value. Conclusions and Relevance:Mild ePH was associated with RV dysfunction and worse RV-pulmonary arterial coupling in a clinical population seeking care. Future studies are needed to identify patients with mild ePH who are susceptible to adverse outcomes.

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17?-estradiol preserves right ventricular function in rats with pulmonary arterial hypertension: an echocardiographic and histochemical study.

Publications

17β-estradiol preserves right ventricular function in rats with pulmonary arterial hypertension: an echocardiographic and histochemical study.

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