Heart failure: metabolic derangements and therapeutic rationale

In the USA, over two-thirds of patients with heart failure (HF) are cared for by primary care practitioners exclusively. Significant progress has been made through basic science and clinical research focusing on the prevention of HF via control of known risk factors. There has also been a great deal of progress in both pharmacologic and nonpharmacologic management of the disease. These therapeutic interventions, however, continue to be underutilized, with seemingly inadequate translation of new evidence and updated guidelines (American College of Cardiology/American Heart Association, European Society of Cardiology, Canadian Cardiovascular Society, and Heart Failure Society of America updates in 2005–2006) into clinical practice. In this review, we discuss the pathophysiology of HF in addition to the metabolic derangements and therapeutic rationale surrounding current treatment options, with a particular focus on the interventions that have been shown and recommended in updated guidelines to prevent the disease or halt its progression.     

Assessing reverse remodeling in heart failure patients treated with cardiac resynchronization therapy and its impact on prognosis

Cardiac resynchronization therapy (CRT) has become an alternative for patients with systolic dysfunction and persistence of heart failure symptoms despite optimal medical therapy. The role of noninvasive cardiac imaging before device implantation still remains controversial, but they are essential to provide an objective evidence of reverse remodeling of the heart which is, in turn, also related to the outcome of patients treated with CRT. The objective of this review is to highlight the acute and long-term CRT benefits as assessed by imaging, with special focus in cardiac reverse remodeling and its impact on prognosis.     

Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts

Galanin is a regulatory peptide with wide distribution in the central and peripheral nervous system and with numerous biological effects. Several radioimmunoassays based on antisera raised against porcine galanin have been used to measure immunoreactivity in rat tissues. However, considerable lack of parallelism has been observed between the porcine standard and rat tissue extracts, which may decrease the reliability of the quantitative data. The purpose of the present study was therefore to raise antibodies against rat galanin and establish a competitive radioimmunoassay for rat galanin. Two antisera, RatGal4 and RatGal5, were characterized in detail. The homogeneity of the immunoreactive material from several tissues was also investigated with column chromatography. At reverse-phase high-pressure liquid chromatography more than 95% of the immunoreactive material from rat CNS eluted as a single peak in the position of synthetic rat galanin, whereas almost half of the immunoreactive material from the intestine eluted in positions different from the synthetic peptide. Extracts of rat brains as well as jejunum diluted in parallel with the standard curve for both antisera. We conclude that measurements of rat galanin based on these antisera are therefore more reliable than those based on antisera raised against porcine galanin.     

基于巨噬细胞极化研究“赤芍-附片”治疗慢加急性肝衰竭的作用机制

目的 研究赤芍-附片对慢加急性肝衰竭（ACLF）大鼠的治疗作用及其对M1/M2型巨噬细胞极化的影响。方法 将SD雄性大鼠随机分为正常组、模型组、乳果糖组（乳果糖 1.8 g·kg^-1）、中药组（赤芍-附片 5.85 g·kg^-1），每组6只。采用牛血清白蛋白皮下及尾静脉注射联合腹腔注射D-半乳糖+脂多糖急性攻击建立ACLF模型，并予以相应药物灌胃1周，空白组和模型组予以蒸馏水灌胃。利用苏木素-伊红（HE）染色观察肝组织病理变化，实时荧光定量聚合酶链式反应（Real-time PCR）、蛋白免疫印迹法（Western blot）、免疫组化等方法比较各组大鼠肝组织CD86、诱导型一氧化氮合酶（iNOS）、CD206、精氨酸酶1（Arg1） mRNA和蛋白表达水平。结果 与正常组比较，模型组大鼠肝组织假小叶形成，肝细胞形态变化、坏死，伴大量炎性细胞浸润，CD86、iNOS mRNA及蛋白表达均显著上调（P<0.01）；与模型组比较，各给药组肝组织坏死及炎性浸润均改善，CD86、iNOS mRNA及蛋白表达下调（P<0.01），而CD206、Arg1 mRNA及蛋白表达上调（P<0.05，P<0.01），与乳果糖组比较，中药组上调CD206、Arg1作用更优（P<0.01）。结论 ACLF大鼠存在M1/M2型巨噬细胞极化失衡，失衡向M1方向偏移，赤芍-附片通过促进肝脏巨噬细胞向M2方向极化，抑制M1型巨噬细胞活化，减轻肝衰竭炎症反应。     

Mortality predictors in complicated patients after anatomical lung resection

IntroductionFailure to rescue (FTR), defined as the mortality rate among patients suffering from postoperative complications, is considered an indicator of the quality of surgical care. The aim of this study was to investigate the risk factors associated with FTR after anatomical lung resections.MethodPatients undergoing anatomical lung resection at our center between 1994 and 2018 were included in the study. Postoperative complications were classified as minor (grade I and II) and major (grade IIIA to V), according to the standardized classification of postoperative morbidity. Patients who died after a major complication were considered FTR. A stepwise logistic regression model was created to identify FTR predictors. Independent variables included in the multivariate analysis were age, body mass index, cardiac, renal, and cerebrovascular comorbidity, ppoFEV1%, VATS approach, extended resection, pneumonectomy, and reintervention. A non-parametric ROC curve was constructed to estimate the predictive capacity of the model.ResultsA total of 2.569 patients were included, of which 223 (8.9%) had major complications and 49 (22%) could not be rescued. Variables associated with FTR were: age (OR: 1.07), history of cerebrovascular accident (OR: 3.53), pneumonectomy (OR: 6.67), and reintervention (OR: 12.26). The area under the ROC curve was 0.82 (95% CI: 0.77–0.88).ConclusionsOverall, 22% of patients with major complications following anatomical lung resection in this series did not survive until discharge. Pneumonectomy and reintervention are the most significant risk factors for FTR.     

Nitric oxide—mediated renal epithelial cell injury during hypoxia and reoxygenation

The potent endothelial-derived vasodilator nitric oxide (NO) has been identified as a protective agent in acute renal failure. However, some recent studies have suggested a detrimental effect of NO on rat proximal tubules exposed to hypoxia and reoxygenation. We determined whether NO metabolites cause intracellular oxidation during hypoxia and reoxygenation and whether this oxidative stress is linked to irreversible cell injury. Primary cultures of rat proximal tubular epithelial cells were studied in a subconfluent stage and subjected to 60 min hypoxia and 30 min reoxygenation. Intracellular oxidation was assessed by monitoring the conversion of nonfluorescent dihydrorhodamine 123 (DHR) to fluorescent rhodamine 123 as a probe for the long-lived oxidant peroxvnitrite. Hypoxia and reoxygenation produced a marked increase in cellular generation of oxidant species. Intracellular oxidation of DHR was reduced by approsimately 40% when cells were also exposed to the NO svnthase inhibitor L-NAME. Oxidation of DHR following hypoxia and reoxygenation was not affected by SOD or DATTU. A combination of SOD and L-NAME was no more effective than L-NAME alone. Hypoxia and reoxygenation produced substantial injury (as LDH release). There was a 40% reduction in LDH release when cells were pretreated with a NO synthase inhibitor. In summary, increased generation of NO capable of inducing intracellular oxidizing reactions and cell death occurred during renal hypoxia and reoxygenation.     

基于网络药理学及实验验证探究芪苈强心胶囊治疗射血分数保留型心衰的作用机制

目的 基于网络药理学及实验验证探讨芪苈强心胶囊治疗射血分数保留型心衰（heart failure with preserved ejection fraction,HFpEF）的作用机制。方法 将44个明确鉴定的芪苈强心胶囊体内代谢物检识有效成分，利用Swisstargetprediction、pharmmapper平台预测化合物靶点，OMIM、DisGenet、GenCard数据库中检索HFpEF疾病靶点；取交集靶点，利用String数据库和Cytoscape 3.7.2软件进行蛋白质-蛋白质相互作用（protein-protein interaction,PPI）和拓扑分析；Metescape平台对共同靶点进行基因本体（gene ontology,GO）功能富集分析及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。构建醋酸脱氧皮质酮（deoxycorticosterone acetate,DOCA）盐敏感型HFpEF大鼠模型，给予沙库巴曲缬沙坦或芪苈强心胶囊进行干预，给药8周后，利用小动物超声成像系统...