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Item The efficiency of endothelin receptor antagonist bosentan for pulmonary arterial hypertension associated with congenital heart disease: A systematic review and meta-analysis(Wolters Kluwer, 2018-03) Kuang, Hong-Yu; Wu, Yu-Hao; Yi, Qi-Jian; Tian, Jie; Wu, Chun; Shou, We Nian; Lu, Tie-Wei; Pediatrics, School of MedicineBACKGROUND: Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was conducted for a therapeutic evaluation of oral bosentan in both adult and pediatric patients with PAH-CHD. The acute responses and a long-term effect were respectively assessed in a comparison with baseline characteristics, and the improvement of exercise tolerance was analyzed. METHODS: PubMed, Medline, Embase, and Cochrane Central Register of clinical controlled trails or observational studies have been searched for a recording of bosentan effects on the PAH-CHD participants. For mortality and rate of adverse events (AEs), it was described in detail. Randomized-effects model or fixed-effects model was used to calculate different effective values with a sensitivity analysis. RESULTS: Seventeen studies were pooled in this review, and 3 studies enrolled the pediatric patients. Among all studies, 456 patients were diagnosed with PAH-CHD, and 91.7% were treated with oral bosentan. With a term less than 6 months of bosentan therapy, there existed a significant improvement in 6-minute walk distance (6MWD) and the World Health Organization functional class (WHO-FC), but no such differences in Borg dyspnea index scores (BDIs) and the resting oxygen saturation (SpO2). Although with a prolonged treatment, not only 6MWD and FC, but also the resting SpO2 and heart rate were changed for a better exercise capability. Additionally, compared with the basic cardiopulmonary hemodynamics, it showed a statistically significant difference in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRi). Although a limitation of pooled studies with comparative outcomes of different terms, outcomes presented a lower WHO-FC which contributes to a success in a prolonged treatment. CONCLUSIONS: Bosentan in PAH-CHD is well established and still requires clinical trials for an identification of its efficiency on CHD patients for an optimized period lessening a serious complication and the common AEs.Item Estradiol improves right ventricular function in rats with severe angioproliferative pulmonary hypertension: effects of endogenous and exogenous sex hormones(American Physiological Society, 2015-05) Frump, Andrea L.; Goss, Kara N.; Vayl, Alexandra; Albrecht, Marjorie; Fisher, Amanda; Tursunova, Roziya; Fierst, John; Whitson, Jordan; Cucci, Anthony R.; Brown, M. Beth; Lahm, Tim; Department of Physical Therapy, School of Health and Rehabilitation SciencesEstrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2’s RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg−1·day−1). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH.Item Six-Minute Walk Test as a Predictive Measure of Exercise Capacity in Adults with Type 2 Diabetes(Wolters Kluwer, 2018-07) Nolen-Doerr, Eric; Crick, Kent; Saha, Chandan; de Groot, Mary; Pillay, Yegan; Shubrook, Jay H.; Donley, David; Hornsby, W. Guyton; Biostatistics, School of Public HealthObjective: The 6 Minute Walk Test (6MWT) is a measure that is routinely used to assess a response to treatment for cardiopulmonary diseases such as pulmonary fibrosis and congestive heart failure. The measure has never been verified as a valid measure of exercise capacity in the highly prevalent patient population of type 2 diabetes (T2DM). This study investigated the correlation between the 6MWT and graded exercise testing (GXT) in an effort to validate the 6MWT as a quality tool for assessing exercise capacity in adults with T2DM. Research Design and Method: This is a secondary data analysis of Program ACTIVE II, a randomized controlled trial designed to assess the effectiveness of two behavioral interventions on depression and glycemic outcomes in adults with T2DM. The correlation of 6MWT and predicted VO2 max (PVO2M) using GXT was examined in a subsample of participants at the time of study enrollment and at post-intervention. Results: PVO2M showed a significant correlation with 6MWT distance both at baseline (r=0.57, p=0.014) and post-intervention (r = 0.66, p = 0.037). The regression analysis of baseline data revealed that 6MWT distance alone explained 45% (F = 13.03, p = .0024) of the variability in PVO2M. When combined with the SF-12 physical health component score (PCS), 6MWT explained 66% (F = 13.62, p < .001) of the variance in PVO2M. After adjusting for PCS, 6MWT distance explained an additional 30% variability in PVO2M. Conclusions: Findings from this study indicate that the 6MWT and predicted exercise capacity are significantly correlated. The 6MWT can be used to estimate exercise capacity in adults with T2DM.