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BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH) are caused by progressive right ventricular (RV) pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. The use of a mitoK(ATP) channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV remodeling during the early stages of PAH.

Objective: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. Methods: We selected 122 cases admitted to the ICU, ages 60-93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient's pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Results: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. Conclusions: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia-induced pulmonary arterial hypertension (PAH) rat model. Ninety-six Sprague-Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)-1β and IL-10. Immunohistochemical analysis for ED1+ monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia-induced PAH rats. Iptakalim also prevented an increase in IL-1β and a decrease in IL-10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia-induced PAH rats. Furthermore, iptakalim enhanced PECAM-1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM-1 and eNOS, suggesting that iptakalim may represent a potential therapeutic agent for PAH. [ABSTRACT FROM AUTHOR]

Objective: Linezolid is active against drug-resistant gram-positive bacteria. However, the efficacy and safety of linezolid in the treatment of the elderly have not been well characterized. The purpose of this study was to evaluate the efficacy of linezolid in the treatment of the elderly with gram-positive bacterial infection and to investigate the risk factors associated with the development of thrombocytopenia in these patients. Methodology: This was a retrospective analysis of 50 elderly patients who were treated with intravenous linezolid for gram-positive bacterial infection. Clinical data and bacteriological responses were assessed. Risk factors associated with thrombocytopenia in elderly patients were analyzed. Results: The overall clinical cure rate of linezolid was 74%, and the bacteriological eradication rate was 69%. Thrombocytopenia occurred in 24 patients, and thrombocytopenia wasassociated with both the duration of treatment (P = 0.005) and the baseline platelet count (P = 0.042). Based on a logistic regression analysis, the baseline platelet count < 200×109/L (OR = 0.244; 95% CI = 0.068- 0.874; P = 0.030) was identified as the only significant risk factor for linezolid-associated thrombocytopenia in elderly patients. The mean platelet count decreased significantly from the 7th day of treatment, and decreased to the lowest value 1-2 days after the end of therapy. Conclusions: Linezolid is effective and safe for the elderly with gram-positive bacterial infections. Adverse effects such as thrombocytopenia are of greater concern. Platelet counts should be monitored in patients who are treated with linezolid and that measures should be taken in advance to avoid hemorrhagic tendencies. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the antibacterial activities and mode of action of sucrose monolaurate (SML) with a desirable purity, synthesized by Lipozyme TL IM-mediated transesterification in the novel ionic liquid, against four pathogenic bacteria including L. monocytogenes, B. subtilis, S. aureus, and E. coli. The antibacterial activity was determined by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and the time–kill assay. SML showed varying antibacterial activity against tested bacteria with MICs and MBCs of 2.5 and 20 mM for L. monocytogenes, 2.5 and 20 mM for B. subtilis, 10 and 40 mM for S. aureus, respectively. No dramatic inhibition was observed for E. coli at 80 mM SML. Mechanism of bacterial inactivation caused by SML was revealed through comprehensive factors including cell morphology, cellular lysis, membrane permeability, K+ leakage, zeta potential, intracellular enzyme, and DNA assay. Results demonstrated that bacterial inactivation against Gram-positive bacteria was primarily induced by the pronounced damage to the cell membrane integrity. SML may interact with cytoplasmic membrane to disturb the regulation system of peptidoglycan hydrolase activities to degrade the peptidoglycan layer and form a hole in the layer. Then, the inside cytoplasmic membrane was blown out due to turgor pressure and the cytoplasmic materials inside leaked out. Leakage of intracellular enzyme to the supernatants implied that the cell membrane permeability was compromised. Consequently, the release of K+ from the cytosol lead to the alterations of the zeta potential of cells, which would disturb the subcellular localization of some proteins, and thereby causing bacterial inactivation. Moreover, remarkable interaction with DNA was also observed. SML at sub-MIC inhibited biofilm formation by these bacteria.