Pulmonary arterial hypertension (PAH) is characterized by vascular cell growth and proliferation leading to increased pulmonary vascular resistance, increased pulmonary arterial pressure, right ventricular failure, and death. The main objective of the study was to investigate the prophylactic and therapeutic benefits of over expression of EC-SOD in an animal model with chronic PAH. Chronic PAH was induced by exposing adult male C57BL6 mice to hypoxia (FiO 2 10%) for 3 weeks and Sugen administration, once per week (3 doses). Hemodynamic, histologic, immunohistochemistry, NO Pathway, angiogenesis markers and inflammatory marker studies were performed at 3, 7, 11-and 14-weeks post-exposure. Transgenic mice which overexpress EC-SOD showed less evidence of PAH, associated with mild inflammation which was resolved by 11-14 weeks post exposure compared with wildtype mice under the same conditions. Overexpression of EC-SOD postestablishment of chronic progressive PAH showed significant therapeutic benefits. There was a significant decrease in pulmonary pressures associated with resolution of the chronic changes at the level of the parenchyma in transfected hypoxic wild type animals compared to wild type hypoxic non-transfected. The data suggest that EC-SOD has a marked and a significant role in ameliorating and reversing the chronic, progressive form of PAH. in murine mo del.
Introduction: Outcomes of mechanical circulatory support (MCS) to treat myocarditis are not well described. Hypothesis: We hypothesize that MCS is increasingly utilized for the treatment of myocarditis and is associated with high morbidity and mortality. Methods: This study utilized admissions from the National Inpatient Sample (NIS) from 2012-2016. Patient-encounters with myocarditis were identified using ICD-9/10 codes. Weighted population estimate outcomes comparing encounters with MCS or without MCS were calculated. Mode of MCS was examined and trends in MCS treatment, mortality and morbidity were assessed using logistic regression models. Results: Of the 48,965 encounters for myocarditis between 2012 and 2016, 1,910 patients died (3.9%) and 255 (0.5%) underwent transplant. MCS was used in 2,215 patients (4.5%): extra corporeal membrane oxygenation (ECMO) in 590, durable ventricular assist device (VAD) in 150, temporary VAD (tVAD) in 320, and intra-aortic balloon pump (BP) in 770. Over 5 years there was no change in the frequency of MCS and mortality in MCS patients remained stable (p for trends >0.3 ). However, the use of ECMO increased from 23.2% in 2012 to 38.5% in 2016 while BP use decreased from 60.9% to 26.4% (p trend for both <0.05). Mortality (25.5% vs 2.9%), infection (32.7% vs 11.7%), stroke (10.2% vs 2.2%), bleeding events (16.0% vs 2.2%) and arrhythmia (58.9% vs 29.0%), were higher in MCS (p for all <0.0001). Incidence of mortality, stroke, and bleeding differed by mode of MCS support {ECMO (31.2%, 15.3%, 23.7%), BP (18.2%, 4.6%, 7.8%), tVAD (26.6%, 4.7%, 7.8%) and VAD (6.7%, 6.7%, 16.7%) (p for all <0.05)} with ECMO having the highest number of complications. Conclusion: MCS is utilized in 5% of patients with myocarditis. ECMO has become the most common support modality, but its use is associated with significant morbidity and mortality. Further evaluation of how patient characteristics influence the MCS type utilized and their impact on outcomes is needed.
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