Endothelial dysfunction plays a principal role in the pathogenesis of pulmonary arterial hypertension (PAH), which is a fatal disease with limited effective clinical treatments. Mitochondrial dysregulation and oxidative stress are involved in endothelial dysfunction. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key regulator of cellular energy metabolism and a master regulator of mitochondrial biogenesis. However, the roles of PGC-1α in hypoxia-induced endothelial dysfunction are not completely understood. We hypothesized that hypoxia reduces PGC-1α expression and leads to endothelial dysfunction in hypoxia-induced PAH. We confirmed that hypoxia has a negative impact on endothelial PGC-1α in experimental PAH in vitro and in vivo. Hypoxia-induced PGC-1α inhibited the oxidative metabolism and mitochondrial function, whereas sustained PGC-1α decreased reactive oxygen species (ROS) formation, mitochondrial swelling, and NF-κB activation and increased ATP formation and endothelial nitric oxide synthase (eNOS) phosphorylation. Furthermore, hypoxia-induced changes in the mean pulmonary arterial pressure and right heart hypertrophy were nearly normal after intervention. These results suggest that PGC-1α is associated with endothelial function in hypoxia-induced PAH and that improved endothelial function is associated with improved cellular mitochondrial respiration, reduced inflammation and oxygen stress, and increased PGC-1α expression. Taken together, these findings indicate that PGC-1α may be a new therapeutic target in PAH.
Background: This study aimed to identify risk factors for prolonged mechanical ventilation (PMV) and its association with disease prognosis following acute DeBakey type I aortic dissection surgery. Methods: A total of 582 patients who received emergency surgery for acute DeBakey type I aortic dissection from 2014 to 2018 were enrolled in this study. Mechanical ventilation period after surgery longer than 48 hours was defined as postoperative PMV. Multiple logistic regression analysis was used to identify risk factors for PMV. This study also compared short-and long-term outcomes in patients who developed PMV with patients who did not develop this complication. To identify and compare long-term cumulative survival rate, Kaplan-Meier survival curve was plotted.Results: Among all enrolled patients, 259 (44.5%) received PMV treatment. Our data suggested that the length of intensive care unit and hospital stay were longer for patients who received PMV treatment. Thirtyday mortality was also higher in patients with PMV than in patients without PMV. Elevated leukocyte count and increased serum cystatin C level upon admission, lower preoperative platelet count and longer cardiopulmonary bypass (CPB) duration were identified as risk factors for PMV. Interestingly, our data suggested that there was no significant difference of survival rate between patients with or without PMV history. Conclusions: PMV after DeBakey type I aortic dissection repair surgery was a common complication and associated with increased short-term mortality rate but did not affect long-term mortality rate. Elevated preoperative leukocyte count, increased preoperative serum cystatin C level, lower preoperative platelet count and longer CPB duration were risk factors for PMV.
OBJECTIVE:We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis.METHODS:Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599.RESULTS:T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05) and better left ventricle function (p<0.01).CONCLUSIONS:The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients.
This study reviews our results and experience with cardiothoracic surgery via RVIAT over the past 15 years. This retrospective overview summarises our results, describing the early and late clinical outcomes of 1,126 patients, including 370 ASD closures, 488 VSD closures and 268 valve surgeries, at a single center between October 2001 and December 2015. The mean follow-up time was 52 ± 35 months (range 8–120 months). The mean incision length was 6 ± 2.22 cm (range 3.9–8.9 cm). No patient required conversion to median sternotomy. All patients were satisfied with the cosmetic results at the follow-up assessment. No chest deformity or asymmetrical development of the breast was observed. Although there was no severe morbidity and operative mortality, ten late deaths occurred, 8 of which were due to cardiac causes and the other 2 to non-cardiac causes. RVIAT offers encouraging short- and long-term patient survival results and is a safe and reproducible approach with excellent late results. RVIAT should be considered as an alternative to conventional median sternotomy.
Compared with norepinephrine, vasopressin could not improve the postoperative outcomes in patients with pLVD after cardiac surgery. Vasopressin should be cautious to be used as a first-line vasopressor agent in postcardiac vasoplegic shock.
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