Role of dendritic cells in lipopolysaccharide induced cardiac dysfunction in mice / 中华危重病急救医学

Objective To observe the role of dendritic cells (DC) in lipopolysaccharide (LPS)-induced myocardial dysfunction in mice. Methods Eighty wild type male C57BL/6 mice were divided into four groups, according to random number table method: sham group, DC inhibitors in control group (VAG539-sham group), LPS sepsis model group (LPS group) and DC inhibitors pretreatment group (VAG539-LPS group), 20 in each group. The cardiac dysfunction model of sepsis mice was established by LPS intraperitoneal injection; the sham group was injected with the same dose of normal saline. VAG539-sham group and VAG539-LPS group were injected with the DC inhibitor VAG539 (30 mg/kg, twice per day, for 2 days) before injection with normal saline or LPS, respectively. Ten mice in each group were used to observe the 14-day survival rate. Mean arterial pressure (MAP) of the remaining 10 mice was measured through the small animal tail artery cannula; the cardiac function [including the heart rate (HR), left ventricular ejection fraction (LVEF) and short axial shortening rate (FS)] were evaluated by small animal echocardiography; the aggregation and maturation of myocardial DC were detected by flow cytometry; and serum inflammatory factors [including tumor necrosis factor-α (TNF-α), interleukins (IL-12, IL-6)] were detected by enzyme linked immunosorbent assay (ELISA). Results Compared with sham group, the 14-day cumulative survival rate in LPS group was significantly reduced, while HR, MAP, LVEF and FS were significantly decreased, and the number of DC in myocardial tissues was significantly increased, and the levels of serum inflammatory factors were increased significantly. The 14-day cumulative survival rate in VAG539-LPS group was significantly higher than that in the LPS group (55% vs. 15%, P < 0.05). Compared with LPS group, after pretreatment by VAG539, the HR, MAP, LVEF and FS were significantly increased [HR (bpm): 610±25 vs. 556±28, MAP (mmHg, 1 mmHg = 0.133 kPa): 68±6 vs. 42±2, LVEF: 0.48±0.02 vs. 0.30±0.03, FS: (34±3)% vs. (14±2)%, P < 0.05]; the number of DC in myocardial tissue was significantly decreased from 6.5% to 3.7%; the level of serum inflammatory factors were significantly decreased [TNF-α(ng/L): 192.00±25.45 vs. 291.34±23.12, IL-12 (ng/L): 58.44±12.37 vs. 78.43±11.24, IL-6 (ng/L): 46.97±8.12 vs. 149.12±15.45, all P <0.05]. Conclusion Sepsis can cause cardiac dysfunction, and it can play an important role by inhibiting the DC cell function of myocardium and reducing the expression of inflammatory factors.

A retrospective analysis of cardioversion for paroxysmal supraventricular tachycardia in emergency department / 中华急诊医学杂志

Objective To analyze retrospectively the cardioversion for paroxysmal supraventricular tachycardia (PSVT) in emergency department in order to explore rational guidance for the diagnosis and treatment for PSVT.Methods A retrospective analysis of PSVT patients in the emergency department admitted from June 2015 to December 2015 was carried out.First,all the patients were divided into two groups according to the cardioversion achieved by Valsalva's maneuvre or not.Forty patients were enrolled in study.There were 11 patients got cardioversion successfully achieved by the Valsalva's maneuvre and 29 patients failed to get cardioversion.Then,comparisons of demographics,vital sign,serum CTNI,potassium and NTproBNP level were carried out between these groups of patients using statistical analysis.The categorical variable was expressed in percentage and the continuous variable was described by mean±standard deviation and the comparisons of parameters were conducted by group t-test and chi-square test.Results The success rate of PSVT maneuvre cardioversion was 27.5％.In addition,there were no significant differences in demographics vital sign,TNI and NTproBNP between the two groups while there were significant differences in serum potassium level between the two groups [(3.8±0.4)mmol/L vs.(3.5±0.35)mmol/L P＜0.05].There was no significant difference in successful rate of cardioversion between the standard Valsalva's maneuvre(n=6) the modified Valsalva's maneuvre(n=5).The second-line treatment mainly included propafenone,adenosine,electroversion,verapamil and amiodarone.The propafenone was the most common second-line agent used for PSVT cardioversion accounting for 58.6％.Conclusions The success rate of Valsalva's maneuver cardioversion was low.Keeping properly a higher level of serum potassium could increase the success rate of cardioversion by Valsalva's maneuvre.

The mechanisms of LPS-induced cardiac dysfunction in septic mice / 中华急诊医学杂志

Objective To study about the cardiac function of the mice suffering from sepsis induced by lipopolysaccharide (LPS) so as to probe the physiopathologic mechanism of the cardiac dysfunction of the mice.Method Sixty male C57BL/6 mice of eight weeks old were randomly (random number) divided into four groups:one control group (n =15) and three experimental groups (n =15 in each group).The mice of control group received intra-peritoneal injection of normal saline (10 mg/kg) while the mice of experimental groups got intra-peritoneal injection of LPS (10 mg/kg).The cardiac function of mice (n =12) was determined by echocardiography 6 h,12 h and 24 h later,respectively.The heart,kidney and lung tissues of mice (n =6) were stained with Haematoxylin-Eosin (HE) staining after embedding with paraffin for observing the histopathological changes under optic microscopy.The expressions of PECAM-1 and α-SMA of the heart tissue of mice (n =3) in three groups determined by immunohistochemical method.The RT-PCR method was used to test the expressions of VEGF (vascular endothelial growth factor) and HIF-α (hypoxia-inducible factor) of the myocardium of mice.In addition,the Western blot method was employed to test the levels of p53 and HIF-1α proteins in myocardium of mice,while ELISA was utilized to detect the level of tumor necrosis factor-α (TNF-α) and the interleukin-6 (IL-6).The data were analyzed by independent samples of t-test and one-way ANOVA respectively.Results The experiment result proved that the thickness of anterior wall of left ventricle of mice during systolic and diastolic periods increased and the inner diameter of the left ventricle also increased during the diastolic period in mice of the experimental group,while the stroke volume decreased compared with the control group (P ＜ 0.05).The immunohistochemical method showed that the new vessels of the mice' s heart in experimental groups increased compared with the control group (P ＜ 0.05).RT-PCR showed the expressions of VEGF and HIF-1α of the mice heart of experimental group increased (P ＜ 0.05) and Western blot showed the levels of HIF-1 α and p53 proteins in experimental groups increased significantly compared with the control group.The experimental group had higher levds of VEGF,HIF-1α,and IL-6 were evidenced by using ELISA than those of the control group (P ＜ 0.05).Conclusions The lipopolysaccharide can lead to cardiac dysfunction.In this process,myocardium angiogenesis and apoptosis phenomenon coexists,as VEGF and HIF-1α participating in angiogenesis,whereas BAX and p53 playing a role in the process of apoptosis.

The role of angiogenesis in myocardial injury in septic mice / 中华急诊医学杂志

Objective To investigate the angiogenesis,apoptosis and their mechanisms in septic mice with myocardial injury.Methods Forty male C57BL/6 mice aged 8 weeks were randomly ( random number) divided into two groups:the sepsis group and the control group.The mice of sepsis group were treated with lipopolysaccharide (LPS) ( 10 mg/kg Intraperitoneal injection) while the mice of control group were treated with saline solution instead (10 mg/kg Intraperitoneal injection).Cardiac function of mice (n =40) was evaluated with ultrasound 6 hours after LPS administration.Subsequently,the tissues of heart,lung and kidney of mice (n =6) were taken and treated with Haematoxylin -Eosin staining (H&E) in order to observe the pathological changes and verify the successfulness of modeling.Immunohistochemistry staining with PECAM - 1 and α - SMA was used to identify the angiogenesis in the heart ( n =3 ),while the TUNEL apoptosis assay was applied for detecting the myocardial cell apoptosis ( n =3 ).The mRNA was extracted from heart tissue (n =6) to observe the expression of HIF-1 ot which was proved to be an angiogenesis factor.All the results were analyzed by independent sample t - test.Results Compared to the control group,mice in the sepsis group showed increased in thickness of left ventricular diastolic anterior wall ( t =- 4.60,P ＜ 0.05 ) and thickness of left ventricular systolic anterior wall (t =-3.24,P ＜0.05 ) along with decrease in left ventricular end diastolic diameter ( t =3.57,P ＜ 0.01 ) and stroke volume ( t =5.51,P ＜ 0.01 ).Immunohistochemistry staining with alpha - SAM antibody revealed increase in cardiac angiogenesis in the sepsis group (t =- 11.00,P ＜ 0.01 ).TUNEL apoptosis assay demonstrated apoptosis of the cardiomyocytes [ sepsis group versus control group:( 191.31 ±5.41 ) vs ( 52.24 ±4.32) ] and RT - PCR showed an increase in the expression of HIF - 1 alpha in the mice of the sepsis group ( t =- 8.12,P ＜0.05) Conclusions There were apparent myocardial angiogenesis,apoptosis and cardiac dysfunction in septic animal models.HIF-1α might play a role in the angiogenesis pathway.