OBJECTIVE: To investigate the effects of total flavonids of astragalus(TFA) on arrhythmia, endoplasmic reticulum stress and connexcin in mice with viral myocarditis and to clarify the mechanisms of TFA against viral myocarditis complicated with arrhythmia. METHODS: Thirty-six male Balb/c mice were randomly divided into control group, viral myocarditis group and total flavonoids group (=12). The mice of viral myocarditis were intraperitonealy injected with 0.1 ml/day 10-950 TCID CVB3 for 3 days. The mice of TFA group were intraperitoneal injected with 0.1 ml/day 10-950 TCID CVB3 for 3 days and treated with 0.1ml, 20 mg/L TFA by tail vein injection. At the end of the experiment, arrhythmia was detected by electrocardiogram, the heart of mice were stained by HE, the expressions of glucose-regulated protein 78(GRP78), endoplasmic reticulum stress signaling pathway factor activating transcription factor 4(ATF4) and connexcin 43(Cx43) were detected by Western blot. RESULTS: The expressions of GRP78 and ATF4 were increased and the expression of Cx43 was decreased in viral myocarditis, while TFA inhibited these effect of viral myocarditis in heart of mice. CONCLUSIONS The antiarrhythmic effect of TFA may be related to the alleviation of endoplasmic reticulum stress and the increase of Cx43 expression.
Activating Transcription Factor 4 ; metabolism ; Animals ; Arrhythmias, Cardiac ; drug therapy ; Astragalus Plant ; chemistry ; Connexin 43 ; metabolism ; Coxsackievirus Infections ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Flavonoids ; pharmacology ; Heat-Shock Proteins ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; drug therapy ; virology ; Myocardium

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%–82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.
Animals ; Base Sequence ; Enterovirus ; Genome ; Heart Failure ; Humans ; Inflammation ; Korea* ; Male ; Meningitis, Aseptic* ; Mice* ; Myocarditis* ; Pathology ; Phenotype ; Virology

OBJECTIVETo investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3).

METHODSThe primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, α-SMA was monitored by immunohistochemistry method. Then the protein expression changes of endoplasmic reticulum chaperone-glucose regulatory protein 78 ( GRP78), calumenin and CX43 were detected by Western blot.

RESULTS(1) Compared with that of the control group, the GRP78 expression level in CVB3 infected group was improved, the expression levels of calumenin and CX43 were all reduced. (2) Compared with that of CVB3 infected group, GRP78 expression level was decreased, and the expression levels of calumenin and CX43 were increased in total flavonoids of astragalus group.

CONCLUSIONCVB3 infection may cause endoplasmic reticulum stress of rat myocardium cells by increasing the expression of GRP78 and decreasing the expression of calumenin and CX43. On the other hand, total flavonoids of astragalus can reduce the expression of GRP78 and increase the expression of calumenin and CX43.The results of this experiment may be closely related to the effects of anti-arrhythmia with viral myocarditis caused by CVB3.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Calcium-Binding Proteins ; metabolism ; Cells, Cultured ; Connexin 43 ; metabolism ; Coxsackievirus Infections ; drug therapy ; Endoplasmic Reticulum ; metabolism ; Endoplasmic Reticulum Stress ; drug effects ; Flavonoids ; pharmacology ; Heat-Shock Proteins ; metabolism ; Mice ; Myocarditis ; drug therapy ; virology ; Myocardium ; cytology ; Myocytes, Cardiac ; drug effects ; virology ; Rats

OBJECTIVETo analyze the reason and treatment of the complications of 61 cases of extracorporeal membrane oxygenation (ECMO) in order to improve survival rate of ECMO treatment.

METHODSECMO records from January 2007 to December 2014 in Shanghai Chest Hospital were investigated retrospectively focusing on complications. There were included 43 male and 18 female patients, age 3 to 66 years. Indications for ECMO included post-operative low cardiac output, viral myocarditis, bridge to heart transplantation, acute respiratory distress syndrome and myocardial infarction. There were 49 cases of veno-arterial ECMO and 12 cases of veno-venous ECMO.

RESULTSECMO duration was 2 to 61 days. Among 43 patients, 37 patients weaned from ECMO successfully and 28 survived to discharge. Various complications occurred to 56 patients, including oxygenator plasma leakage(4 case times), circuit emboli (7), hemolysis (4), bleeding (34), infection (8), acute kidney injury (35), lower limb ischemia (8) and neurologic complications (6). There were 49 cases times of complications in survivors, while 61 cases times in death group. Bleeding (10 time cases) and acute kidney injury (33 time cases) happened in the death group. Progresses in ECMO technique had influences on complications in some parts. For instance, incidence of lower limb ischemia was 6/7 in cutdown cannulating group, but reduced to 2/42(4.8%) when semi-open technique was applied.

CONCLUSIONSComplications in ECMO are relative to patients' outcome intimately. Appropriate prevention and treatment of complication play a major role in the success of ECMO support. The incidences of certain complications reduce significantly due to progresses of equipment and medical experiences.

Acute Disease ; Acute Kidney Injury ; etiology ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Extracorporeal Membrane Oxygenation ; adverse effects ; Female ; Heart Transplantation ; Hemorrhage ; etiology ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Myocarditis ; virology ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo determine the optimum treatment for viral myocarditis (VMC).

METHODSA total of 126 VMC patients were randomly divided into the control group (42 cases) that was treated with conventional Western medicine, and the intervention group (84 cases) that was treated with a combination of Chinese medicine (CM) and Western medicine intervention termed optimum proposal of integration of disease and syndrome (OPIDS). Before and after 4 weeks of treatment, the integral of CM syndrome, self-rating depression and anxiety scales (SDS and SAS, respectively), echocardiograms (ECGs), heart rate variability and left ventricular systolic function were observed.

RESULTSCompared with the control group, the intervention group showed significant reductions on the SDS and SAS (P <0.05); improvement of premature ventricular beats, atrioventricular blocks, ST-segment abnormalities, and significant T wave changes (P <0.05); greater reductions in standard deviation of NN intervals (SDNN), standard deviation for per 5 min averages NN intervals (SDANN), and root-mean-square of successive difference of NN intervals (rMSSD) (P <0.05); and increases in cardiac output, stroke volume, and ejection fraction, the last of which was statistically significant (P <0.05). Overall, the treatment efficacy rate was significantly better P<0.05) in the intervention group (75.61%) compared with the control group (69.70%).

CONCLUSIONOPIDS is quite effective in treating VMC and improves symptoms such as anxiety and depression, left ventricular systolic dysfunction, premature ventricular contraction, and cardiac autonomic nervous system dysfunction. [

REGISTRATIONChinese clinical trial center (No. ChiCTR-TRC-00000298)].

Adolescent ; Adult ; Anxiety ; complications ; Depression ; complications ; Electrocardiography ; Female ; Heart Rate ; Humans ; Male ; Medicine, Chinese Traditional ; Myocarditis ; diagnostic imaging ; physiopathology ; therapy ; virology ; Syndrome ; Systole ; Ultrasonography ; Ventricular Function ; Young Adult

Animals ; Astragalus Plant ; chemistry ; Coxsackievirus Infections ; physiopathology ; Flavonoids ; pharmacology ; Mice ; Mice, Inbred BALB C ; Myocarditis ; physiopathology ; virology ; Myocytes, Cardiac ; drug effects ; virology

OBJECTIVE: Astragaloside is a simple substance of saponin and the active constituent of astragali. It was reported that the astragaloside exerted therapeutical eff ect on viral myocarditis and dilated cardiomyopathy. The purpose of this study was to investigate the effect of astragaloside on TL1A expression in viral myocarditis. METHODS: A total of 100 BALB/c mice were randomly divided into 6 groups: the normal control group (group A, n=10), the high-dose control group (group B, n=10), the myocarditis control group (group C, n=20), the low-dose group (group D, n=20), the middle-dose group (group E, n=20) and the high-dose group (group F, n=20). Mice in group A and group B were injected intraperitoneally with 0.1 mL EMEM solution, while mice in group C, D, E and F were treated with 0.1 mL of 1×102 TCID50 CVB3 (diluted in EMEM). Then, mice in group A and group B were treated with carboxymethycellulose solution and 9% astragaloside for 1 week, respectively. At the same time, mice in group C, D, E and F were treated with sodium carboxymethycellulose solution, 1% [0.07 g/(kg.d)], 3% [0.2 g/(kg.d)] and 9%[0.6 g/(kg.d)] astragaloside for 1 week, respectively. After 14 days, the mice were sacrificed and their hearts were collected. The expression levels of TL1A mRNA and protein in the myocardium were examined by RT-PCR and immunohistochemistry, respectively. RESULTS: There was no death in the group A and B. The mortality in the group C, D, E and F was 45% (9/20), 30% (6/20), 25% (5/20) and 10% (2/20), respectively. Compared with the group C, the mortality in the group F was significantly decreased (P<0.05), but there no significant difference in mortality between the group C and the group D or E (P>0.05). There was no any pathological lesion in the group A and B. The TL1A mRNA and protein expression in the myocardium of mice in the group A and B was at low level, with no difference between them (P>0.05). Compared with the group A, the expression levels of TL1A mRNA and protein in the group C were markedly up-regulated (P<0.01), which was dramatically attenuated by the intervention of astragaloside at high dosage (the group F, P<0.01) but not at low (the group D) or middle-dosage (the group E) (P>0.05). CONCLUSION Astragaloside may play a pivotal role in protection of the heart injury in viral myocarditis by suppressing the expression of TL1A.
Acute Disease ; Animals ; Cardiomyopathy, Dilated ; drug therapy ; Coxsackievirus Infections ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Mice ; Mice, Inbred BALB C ; Myocarditis ; drug therapy ; virology ; Myocardium ; metabolism ; pathology ; RNA, Messenger ; Saponins ; pharmacology ; Tumor Necrosis Factor Ligand Superfamily Member 15 ; metabolism ; Up-Regulation

OBJECTIVETo assess the efficacy and safety of Astragalus membranaceus Injection combined with conventional therapy in the treatment of viral myocarditis.

METHODSRandomized controlled trials (RCTs) of A. membranaceus Injection combined with conventional treatment compared with conventional treatment alone were included. Study population characteristics and outcome results were extracted independently by two assessors. Meta-analysis was performed for data available.

RESULTSSix RCTs, involving 639 participants, were included in this study. The methodological quality of the included trials was generally low, and there was high risk of publication bias in the included trials. The total effective rate of A. membranaceus Injection combined with conventional treatment was significantly higher than that of conventional treatment alone. Compared with conventional treatment, the cointervention treatment group showed significant recovery in myocardium enzyme levels and electrocardiography. Two RCTs reported there were no adverse effects from A. membranaceus Injection combined with conventional treatment.

CONCLUSIONA. membranaceus Injection combined with conventional treatment appeared to be more efficacious compared with conventional treatment alone for treating viral myocarditis. However, this conclusion should be cautiously interpreted due to low methodological quality, small sample size, limited number of trials, and high risk of publication bias and other unidentified risks of bias. The safety of A. membranaceus Injection combined with conventional treatment remains uncertain.

Astragalus membranaceus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Injections ; Myocarditis ; diagnostic imaging ; drug therapy ; virology ; Myocardium ; enzymology ; pathology ; Phytotherapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Ultrasonography

OBJECTIVETo explore the apoptotic pathway mediated by endoplasmic reticulum stress in the mouse myocardium with heart failure induced by acute viral myocarditis caused by B-3 Coxsackie virus.

METHODSForty BALB/c male mice were randomly divided into 2 groups (n = 20): the control group and the virus infection group. The BALB/c mouse myocarditis was induced by B-3 Coxsackie virus and the mouse behavior was observed conventionally. All the mice were sacrificed on day 7 and the changes of left ventricular pressure (LVP) and the rate of change of left ventricular pressure (LV dp/dt) were measured. The cardiomyocytic apoptosis was analyzed by TUNEL method and the mRNA expression level of endoplasmic reticulum haperones glucose-regulated protein (GRP)78 and GRP94 was detected by RT-PCR.

RESULTS(1) Compared with those of control group, the parameters of cardiac hemodynamics in the virus infection group were significantly decreased (P < 0.01); (2) Compared with that of control group, myocardial apoptosis was significantly increased in the myocardial cells from mice with heart failure induced by acute viral myocarditis (P < 0.01); (3) The mRNA expression level of GRP78 and GRP94 were increased significantly in the virus infection group compared with the control group.

CONCLUSIONThese findings suggest the endoplasmic reticulum stress may mediate the apoptosis of myocardial cells in the mice myocardium of heart failure induced by acute viral myocarditis caused by B-3 Coxsackie virus.

Animals ; Apoptosis ; Coxsackievirus Infections ; physiopathology ; Endoplasmic Reticulum Stress ; Heart ; physiopathology ; Heart Failure ; physiopathology ; virology ; Heat-Shock Proteins ; metabolism ; Male ; Membrane Glycoproteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Myocarditis ; physiopathology ; virology ; Myocardium ; pathology ; Myocytes, Cardiac ; cytology

OBJECTIVETo explore the effects of emodin in myocardial protection in mice with viral myocarditis (VMC) and explore molecular mechanisms.

METHODSFifty-five male 4-week-old BALB/c mice were randomly divided into control group (n=15), model group (n=20), and emodin group (n=20). The mice in model and emodin groups were inoculated with 0.1 ml Eagle's solution containing coxsackievirus B3 intraperitoneally, and those in the control group were given only 0.1 ml Eagle's solution. From the day of inoculation, the mice in emodin group received intragastric administration with 0.1 ml of 3 mg/ml emodin solution once daily for 21 consecutive days, and those in the control and model groups received 0.1 ml distilled water only. On day 7 after inoculation, 5 mice from each group were sacrificed to determine the viral titers in the cardiac tissues. All the mice were sacrificed on day 22 for measurement of the heart weight and histopathological inspection of the heart with HE staining. The mRNA and protein expression levels of myocardial interleukin-23 (IL-23) and interleukin-17 (IL-17) were detected by real-time quantitative PCR and Western blotting, respectively, and serum IL-23 and IL-17 levels were examined using enzyme linked immunosorbent assay (ELISA). Th17 cell frequencies were analyzed by flow cytometry. The expression levels of myocardial nuclear factor-κB (NF-κB) p65 in the cardiomyocyte nuclei were examined using Western blotting, and myocardial interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) contents were detected by ELISA.

RESULTSThe mortality, myocardial histopathologic scores and virus titers in emodin group were all significantly lower than those in the model group (P<0.05). The heart-to-body weight ratio, myocardial IL-23 and IL-17 expressions, serum IL-23 and IL-17 levels, Th17 cell frequencies, cardiomyocyte nuclear NF-κB p65 expression, and myocardial contents of IL-1β, IL-6 and TNF-α were all significantly increased in the model group as compared to the control group (P<0.01) but reduced significantly in emodin group as compared to model group (P<0.05).

CONCLUSIONEmodin can protect against VMC by inhibiting IL-23/IL-17 inflammatory axis, Th17 cell proliferation and viral replication in mice.

Animals ; Coxsackievirus Infections ; immunology ; Cytokines ; immunology ; Emodin ; pharmacology ; Enterovirus ; physiology ; Interleukin-17 ; immunology ; Interleukin-23 ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; immunology ; virology ; Th17 Cells ; cytology ; drug effects ; Transcription Factor RelA ; metabolism ; Virus Replication