The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Right ventricular systolic pressure – Non-invasive bedside predictor of mortality and readmission in heart failure with reduced and preserved ejection fraction hospitalization

Objective: To study the prognostic role of right ventricular systolic pressure (RVSP) in patients with heart failure (HF). Background: Although RVSP is a readily available echocardiographic parameter, it is often underused. Its prognostic role in patients with heart failure is not well established compared with pulmonary artery pressure measured by right heart catheterization. Methods: This single-center retrospective cohort study included patients with acute heart failure hospitalization admitted to the hospital from January 2005 to December 2018. The primary predictor was right ventricular systolic pressure (RVSP) obtained from bedside transthoracic echocardiography at admission. We divided RVSP into two groups, RVSP <40 mm Hg (reference group) and RVSP 40 mm Hg. Primary outcome was all-cause mortality. Secondary outcomes were all-cause readmission and cardiac readmission. We conducted propensity-score matching and applied cox-proportional hazard model to compute hazard ratio (HR) with 95% confidence interval (CI). Results: Out of 972 HF patients, 534 patients had RVSP <40 mm Hg and 438 patients had RVSP 40 mm Hg. Patients with RVSP 40 mm Hg compared with RVSP <40 mm Hg were associated with higher rates of death [HR: 1.60, 95% CI: 1.22e2.09, P-value ¼ 0.001], all-cause readmissions [HR: 1.37, 95% CI: 1.09 e1.73, P-value ¼ 0.008] and cardiac readmissions [HR: 1.41, 95% CI: 1.07e1.85, P-value ¼ 0.014]. Conclusion: Higher RVSP (40 mm Hg) in HF patients was associated with higher rates of death, allcause readmissions, and cardiac readmissions. RVSP can be considered as a prognostic marker for mortality and readmission.P

Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension / 药学学报

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

Design and application research of PE right ventricular catheter for mice / 重庆医学

Objective To establish a simple ,low cost and stable method to detect right ventricular pressure in mice .Methods A PE-50 duct length 15 cm(outside diameter :0 .9 mm ,inner diameter :0 .5 mm) was bent on one terminal and the other terminal was inserted into a 7# syringe needle to connect to a pressure transducer .This duct was intubated into right ventricle via right external jugular vein to detect right ventricular pressure in 80 SPF grade male C57BL/6 mice .Successful cases and operation time were re-corded .Besides ,40 SPF grade male C57BL/6 mice were randomized into the control group (n=20) and chronic hyperbaric hypoxia group(n= 20) .Mice in chronic hyperbaric group were raised in a hyperbaric chamber of simulated 5 000 m high altitude for 4 weeks .The control group was raised outside the chamber simultaneously .Right ventricular systolic pressure was detected with the PE duct .Left and right ventricles were detached and weighed ,and Hermann-Willson index was calculated .Results With this PE duct ,right ventricular intubation success rate was 90% (72/80) ,the operation cost approximately 3 to 5 min each mouse from the separation of blood vessels to detect the time needed for the right ventricle waveform .right ventricular systolic pressure[(39 .52 ± 4 .34 )mm Hg] and Hermann-Willson index(0 .356 ± 0 .039)of chronic hyperbaric hypoxia group were significantly higher than that of control group [(21 .24 ± 2 .7)mm Hg and (0 .256 ± 0 .020)] ,which has significant positive correlation (P<0 .01) .Conclusion It is simple ,fast ,stable ,costing low and of high success ratio to detect right ventricular pressure with this method .

Predictors of Long-term Mortality after Hospitalization for Acute Exacerbation of COPD / 결핵및호흡기질환

BACKGROUND: Acute exacerbations form a major component of the socioeconomic burden of COPD. As yet, little information is available about the long-term outcome of patients who have been hospitalized with acute exacerbations, although high mortality rates have been reported. The aim of this study was to determine predictors of long-term mortality after hospitalization for acute exacerbation of COPD. METHODS: We performed a retrospective cohort study of consecutive patients admitted to the hospital for COPD exacerbation between 2000 through 2004. Patients who had died in hospital or within 6-months after discharge, had tuberculosis scar, pleural thickening or bronchiectasis by chest radiography or had been diagnosed with malignancy during follow-up periods were excluded. RESULTS: Mean age of patients was 69.5 years, mean follow-up duration was 49 months, and mean FEV1 was 1.00L (46% of predicted). Mortality was 35% (17/48). In the multivariate Cox regression analysis, heart rate of 100/min or more (p=0.003; relative risk [RR], 11.99; 95% confidence interval [CI], 2.34-61.44) and right ventricular systolic pressure (RVSP) of 35mmHg or more (p=0.019; RR, 6.85; 95% CI, 1.38-34.02) were independent predictors of mortality. CONCLUSION: Heart rate and RVSP in stable state may be useful in predicting long-term mortality for COPD patients admitted to hospital with acute exacerbation.