Meta-analysis of statin combined with trimetazidine on the regulation of inflammatory factors in coronary atherosclerotic heart disease and improvement of ventricular remodeling

Objective:To systematically evaluate the effects of statins combined with trimetazidine on the regulation of inflammatory factors and the improvement of ventricular remodeling in coronary atherosclerotic heart disease based on the inflammasomes/immune damage response theory.Methods:Using computer to search for EMbase,The Cochrane Library,Web of Science,MEDLINE,PubMed,WanFang Data,CNKI,China Biomedical Document Service System(CBM),VIP database(VIP),9 databases in total.The search time limit is from the inception of the databases to June 7,2021.All reference documents included in the study were manually searched.According to the Cochrane systematic review method,the information on atorvastatin combined with trimetazidine and conventional treatment(antiplatelet,control blood pressure,diuresis,coronary artery dilation and other expectant treatments)contrast the use of trimetazidine or stains combined with expectant treatment of coronary atherosclerotic heart disease patients in Chinese and English randomized controlled trials(RCT),and conduct the extraction and quality evaluation of the included literature data,using RevMan5.4 software for Meta analysis.Outcome indicators include inflammatory factors:C-reactive protein(CRP),IL-6(interleukin 6),tumor necrosis factor(TNF-α),and ventricular remodeling related outcome indicators:left ventricular end diastolic diameter(LVEDD),left Ventricular end systolic diameter(LVESD).Results:12 randomized controlled trials were included,a total of 1120 patients with coronary heart disease.Meta-analysis results:(1)inflammatory factors:the statin combined with trimetazidine group can significantly reduce the CRP,IL-6,TNF-α’s expression degree in the blood of patients with coronary heart disease compared with the control group(only statins or trimetazidine).CRP[n=770,SMD=-2.70,95%CI(-2.55,-1.40),P<-0.00001],TNF-α[n=678,SMD=-2.25,95%CI(-3.39,-1.12),P<-0.0001],IL-6[n=770,SMD=-2.10,95%CI(-3.10,-1.10),P<0.00001].(2)Ventricular remodeling:Compared with the control group(using statins or trimetazidine alone),the statin combined with trimetazidine group can significantly reduce the left ventricular end-systolic diameter of patients with coronary heart disease before treatment[n=626,SMD=-1.55,95%CI(-2.10,-0.99),P<-0.00001]and leftVentricular end diastolic diameter[n=626,SMD=-1.18,95%CI(-1.56,-0.80),P<-0.00001].Conclusion:Compared with the control group,statins combined with trimetazidine can significantly reduce the level of inflammatory factors based on the inflammasomes/immune injury response theory,and improve the ventricular remodeling in patients with coronary heart disease.

Shengmai Yin formula promotes ventricular remodeling in chronic heart failure rats by inhibiting excessive autophagy via activating AKT/mTOR pathway

Background:Shengmai Yin(SMY)formula,a traditional Chinese medicine,shows a definite therapeutic effect on chronic heart failure(CHF)in clinical practice,but the molecular mechanism remains largely unknown.The PI3K/Akt/mTOR pathway is a classic pathway of autophagy and plays a pivotal role in the occurrence and development of CHF.Here,we aimed to investigate whether SMY formula treat CHF rats by inhibiting excessive autophagy.Methods:Echocardiography was conducted to evaluate cardiac function.Transmission electron microscopy was used to observe the arrangement of myocardial cells.Enzyme linked immunosorbent assay analysis was performed to quantitative detecting the content of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-α in rat serum.Western blotting was used to detect the expression of AKT,p-AKT,mTOR,p-mTOR,light chain 3(LC3),and p62.In vitro,myocardial cells were treated with hypoxia reoxygenation and then intervened with SMY.Cell counting kit-8 method was used to measure the cell viability.The immunofluorescence expression of LC3 protein were also examined.Results:In vivo,SMY intervention assisted in the ventricular remodeling,reduced the levels of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-αin serum,and recovered myocardial cell structure in CHF rats.Treatment with SMY significantly promoted the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulated the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ.In vitro,when the concentration of SMY containing serum reached 40% in the medium,the activity of myocardial cells reached the highest at 135.14%.SMY inhibited the expression of LC3 in hypoxic-reoxygenation embryonic ventricular myocytes cells.When the hypoxic reoxygenation cells treated with p-mTOR inhibitor,rapamycin,or p-AKT inhibitor,API-1,SMY could also down-regulated the LC3 expression level.Conclusions:SMY formula functions in restoring cardiac function and promoting myocardial ultrastructural recovery by reducing autophagy activity through up-regulating the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulating the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ in CHF rats.

Real-time Three-dimensional Echocardiographic Assessment of Left Ventricular Remodeling Index in Patients with Hypertensive Heart Disease and Coronary Artery Disease

Left ventricular remodeling index （LVRI） was assessed in patients with hypertensive heart disease （HHD） and coronary artery disease （CAD） by real-time three-dimensional echocardiography （RT3DE）. RT3DE data of 18 patients with HHD, 20 patients with CAD and 22 normal controis （NC） were acquired. Left ventricular end-diastolic volume （EDV） and left ventricular end-diastolic epicardial volume （EDVepi） were detected by RT3DE and two-dimensional echocardiography Simpson biplane method （2DE）. LVRI （left ventricular mass/EDV） was calculated and compared. The results showed that LVRI measurements detected by RT3DE and 2DE showed significant differences inter-groups （P〈0.01）. There was no significant difference in NC group （P〉0.05）, but significant difference in HHD and CAD intra-group （P〈0.05）. There was good positive correlations between LVRI detected by RT3DE and 2DE in NC and HHD groups （t=0.69, P〈0.01; r=0.68, P〈0.01）, but no significant correlation in CAD group （r=0.30, P〉0.05）. It was concluded that LVRI derived from RT3DE as a new index for evaluating left ventricular remodeling can provide more superiority to LVRI derived from 2DE.

COMPARISON OF THE EFFECTS OF LOSARTAN,ENALAPRIL AND THEIR COMBINATION IN THE PREVENTION OF LEFT VENTRICULAR REMODELING AFTER ACUTE MYOCARDIAL INFARCTION IN THE RAT

Objectives. To compare the effects of losartan, enalapril and their combination in the prevention ofleft ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat. Methods. AMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups: 1 ) AMI control group (n =19), 2) losartan group (n= 22, 3 mg @ kg - 1 @ d - 1 ), 3 ) enalapril group (n = 20, 1 mg @ kg - 1 @ d - 1 ), 4) losartan - enalapril combinative group (n = 22, 3 and 1 mg @ kg- 1 @ d - 1 respectively). 5 ) sham-operated group ( n =10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1 ) AMI controls (n = 11 ), 2) losartan group (n = 10), 3 ) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11 ),5) sham - operated group (n = 6) and 6) normal controls (n=8). Results. There were no significant differences among the 4 AMI groups in MI size (41.7% ～ 43.4%, all P＞ 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW)in AMI group were all significantly increased ( P ＜0.05 ～ 0. 001 ); whereas the maximum left ventricular pressure rising and droping rates ( + dp/dt) and their corrected values by LV systolic pressure ( + dp/dt/LVSP)were significantly reduced (all P ＜0.001 ), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group , LVEDP, LVV, LVAW and LVRW were all significantly decreased (P ＜0.05～0.001 ); while + dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P ＜0.05～0.001 ) except -dp/dt/LVSP in losartan group (P＞ 0. 05 ). There were no significant differences in the above indices among the 3 treatment groups (all P＞ 0.05). Conclusion. Both losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination.

MicroRNA-29a attenuates angiotensin-Ⅱ induced-left ventricular remodeling by inhibiting collagen,TGF-β and SMAD2/3 expression

Background Left ventricular(LV)remodeling is the most common target organ damage in hypertension.Previously,our study found that plasma microRNA-29a(miR-29a)level was associated with the LV remodeling in hypertensive patients.However,the causal relationship between miR-29a and LV remodeling remains unknown.Thus,the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling.Methods&Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively.Then the mice were subjected to angiotensin-II(AngII)induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks.AngII-induced LV remodeling mice as the model group(n=9).Age-matched male SPF C57/BL6J mice(6–8 weeks old)were treated with the pumping of saline as a vehicle(n=6).In vivo,overexpression miR-29a ameliorated AngII-induced LV remodeling,while knockdown miR-29a deteriorated LV remodeling.Simultaneously,we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area,indicating that miR-29a has an antagonistic effect on cardiac hypertrophy.Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III.Moreover,the expression of transforming growth factor-β(TGF-β)and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice.Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition,TGF-β,and phosphorylated SMAD2/3 expression.Thus,intervention miR-29a may be a therapeutic target for attenuating LV remodeling.

Effects of Tribuli Saponins on Left Ventricular Remodeling after Acute Myocardial Infarction in Rats with Hyperlipidemia

Objective: To observe the effect of Tribuli saponins (TS) on left ventricular remodeling after acute myocardial infarction(AMI) in rats with hyperlipemia.Methods: A composite model of myocardial infarction and hyperlipemia was established and treated with TS to observe its effect on cardiac structure and function by echocardiography.Results: (1) Cardiac function: As compared with the model group, the fractional shortening (FS) and ejection fraction (EF) got increased, and the left ventricular end diastolic volume (LVEDV) and systolic volume (LVESV) got lower in the groups treated with high dose TS and simvastatin ( P<0.05 or P<0.01), but difference between the two treated groups was insignificant. (2) Cardiac structure: As compared with the model group, the left ventricular dimension end diastole (LVDd) and systole (LVDs) in the groups treated with high dose TS and simvastatin got lower (P<0.05 or P<0.01). No treatment showed any effect on the thickness of ventricular wall. (3)Ventricular weight index: Both high dose TS and simvastatin could decrease the left ventricular weight index (LVWI) (P<0.05).Conclusion: TS could attenuate the left ventricular remodeling after acute myocardial infarction to certain extent, and improve cardiac function in the early phase after AMI, thus playing an important role in controlling morbidity and mortality of cardiac events and long-term prognosis.

Therapeutic Mechanism of Yuxingeng Liquid(愈心梗液)on Early Ventricular Remodeling with Acute Myocardial Infarction in Rats

Objective:To examine the therapeutic mechanism of Yuxingeng liquid (愈心梗液,YXGL) on early ventricular remodeling in Wistar rats with acute myocardial infarction(AMI). Methods: Measuring the cardiac index (CI), left ventricular weight (LVW) and cardiac myocyte dimension and observing the concentration of endothelin (ET) and angiotensin E (Ang n ) in the plasma and myocardium. AMI models were established by ligature of left anterior descending coronary artery and the rats with AMI were randomly divided into 6 groups: the model group, sham-operation group, captopril group, high dosage YXGL group, middle dosage YXGL group and low dosage YXGL group. From the next day after modeling, the rats had been given YXGL through the gastric tube, which lasted for 4 weeks. And then, CI, LVW and concentration of ET and Ang II in the plasma and myocardium were tested. Results: Comparing with model control group, high dosage YXGL, middle dosage YXGL and captopril can all significantly reduce CI, LVW, cardiac cell dimension and content of ET and AngII in both plasma and myocardium (P< 0. 05 or P<0. 01). Conclusion: YXGL can remarkably reduce LVW, CI and concentration of ET and Ang II,and lowering the concentration of ET and Ang II is possibly one of the mechanisms intervening the pathological course of the early ventricular remodeling in rats with AMI.

Effect of exercise training on left ventricular remodeling in patients with myocardial infarction and possible mechanisms

BACKGROUND A growing amount of evidence provides support for the hypothesis that acute myocardial infarction(AMI)patients should go through cardiopulmonary exercise testing(CPET)about 3-5 d after AMI is diagnosed,make reasonable exercising prescription,and conduct exercise training under guidance.AIM To investigate the effect of exercise training(ET)on left ventricular systolic function and left ventricular remodeling(LVRM)and to study the possible mechanisms of LVRM by the changes of matrix metallopeptidase 9(MMP-9)and tissue inhibitor of metalloproteinases 1(TIMP-1)in patients with acute STsegment elevation myocardial infarction(STEMI).METHODS Sixty patients with first STEMI undergoing direct percutaneous coronary intervention from February 2008 to October 2008 were randomly assigned to an exercise group(n=30)and a control group(n=30).The levels of MMP-9 and TIMP-1 were measured in all patients at 1 d,10-14 d,30 d,and 6 mo after admission.Two-dimensional echocardiography and cardiopulmonary exercise testing were done in patients at 10-14 d and 6 mo after admission.RESULTS There was no significant difference in CPET at baseline between the exercise group and the control group.At 6 mo,the time of exercise,peak and anaerobic threshold values of O2 uptake,and metabolic equivalents increased in both groups,but markedly increased in the exercise group.At baseline,there were no significant differences in left ventricular ejection fraction(LVEF)between the two groups.At 6 mo,LVEF increased in the exercise group,but not in the control group.At 6 mo,the percentage of patients with positive result of LVRM was 26.6%in the exercise group and 52.6%in the control group(P<0.05).The levels of plasma MMP-9 and TIMP-1 and the ratio of MMP-9 to TIMP-1 in both groups had no significant difference at 1 d and 10-14 d after AMI,but at 30 d and 6 mo,the levels of plasma MMP-9 and TIMP-1 in the exercise group were significantly lower than those in the control group;the ratio of MMP-9 to TIMP-1 in the exercise group was significantly higher than that in the control group.CONCLUSION ET under supervision based on home condition in early and recovery stage of AMI can improve exercise cardiopulmonary function and prevent the LVRM.Therefore,it may reduce unfavorable remodeling response by decreasing the levels of plasma MMP-9 and TIMP-1 and adjusting the ratio of MMP-9 to TIMP-1 hereafter.

Comparative Proteomic Analysis in Left Ventricular Remodeling following Myocardial Infarction in Rats

Objective Left ventricular remodeling （LVR） following myocardial infarction （MI） is a key pathophysiological process in which MI develops into heart failure. The exact mechanism of LVR remains unclear. We performed differential proteomic analysis on the myocardia of rats with LVR after MI, to explore the mechanism of ventricular remodeling after MI. Methods In the LVR group （n=12）, after the anterior descending coronary artery was ligated, the rats were fed for four weeks before the LVR models were established. Rats in the sham-operated group （n=11） underwent thread-drawing without ligation. The hemodynamic parameters, pathological findings, and proteomics were compared between the two groups. Results In the LVR group, the left ventricular end-diastolic pressure increased, the maximal left ventricular pressure increase/decrease ratio decreased significantly, and the left ventricular systolic pressure decreased. H-E staining and Masson staining of cardiac muscle tissues of the LVR group showed myocytolysis, disarray, and collagen proliferation. Twenty-one differentially expressed proteins were detected by proteomic analysis. We validated two proteins using western blot analysis. The differentially expressed proteins could be divided into six categories： energy metabolism-related proteins, cytoskeletal proteins, protein synthesis-related proteins, channel proteins, anti-oxidation- related proteins, and immune-related proteins. Conclusion These differentially expressed proteins might play key roles in LVR following M

Effect of Astragalus Injection on Left Ventricular Remodeling in Aged Patients with Acute Early-stage Myocardial Infarction

Objective: To observe the effect of Astragalus Injection (AI) on left ventricular remodeling in aged patients with acute myocardial infarction (AMI). Methods: Patients with AMI were randomly divided into the AI group (46 cases) treated with AI and the control group (46 cases) treated conventionally. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), anterior endocardial segmental length (ASL) and posterior endocardial segmental length (PSL) were all assessed by echocardiogram after 1 week and 4 weeks treatment. The cardiac systolic and diastolic functions were detected by nuclide gating cardiac blood pool imaging at the 4th week. Results: After four weeks' treatment, no obvious change of LVEDVI, LVESVI and ASL in the AI group was found, but these indexes increased significantly in the control group, with significant difference shown between the two groups (P<0. 05). As compared with the control group, the left ventricular ejection fraction (LVEF), left ventricular peak ejecting rate (LVPER) and left ventricular peak filling rate (LVPFR) were heightened, the time for peak filling rate (LVTPFR) in the left ventricle was shortened in the AI group. Conclusion: AI is one of the effective drugs in reversing left ventricular remodeling in aged patients with AMI.

Influence of Transplantation of Allogenic Bone Marrow Mononuclear Cells on the Left Ventricular Remodeling of Rat after Acute Myocardial Infarction

To probe into the influence of transplantation of allogenic bone marrow mononuclear cells （BM-MNCs） on the left ventricular remodeling of rat after acute myocardial infarction （AMI）, 60 male Wistar rats were evenly divided into three groups at random： control group 1, control group 2 and transplantation group. In control group 1, chest was opened without ligation of coronary artery; in control group 2 and transplantation group, the left anterior descending branch of coronary artery was ligated to establish AMI model. Prepared culture medium and allogenic BM-MNCs suspension were respectively implanted the surrounding area of infracted cardiac muscle via epicardium of control group 2 and transplantation group. Four weeks after the operation, the osteopontin gene （OPN mRNA, P〈0.01）, type Ⅰ collagen （P〈0.01） and angiotensin Ⅱ （AngⅡ, P〈0.01） content in the left ventricular non-infracted myocardium, and the Ang Ⅱ density in blood plasma （P〈0.05） of transplantation group and control group 2 were all significantly higher than that of control group Ⅰ. In the transplantation group, the myocardial OPN InRNA, type Ⅰ collagen and Ang Ⅱ content of non-infracted zone in left ventricle, and the Ang Ⅱ concentration in blood plasma were all significantly lower than those of control group 2 （P〈0.05 for all）. It is concluded that allogenic BM-MNCs transplantation may ease left ventricular remodeling after AMI by inhibiting the synthesis of type Ⅰ collagen in the cardiac muscle and down-regulating the expression of Ang Ⅱ and OPN gene.

Effects of Perindopril on Left Ventricular Remodeling and Osteopontin Expression in Rats With Myocardial Infarction

Objectives To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction. Methods In this study male adult SD rats were randomly divided into 3 groups: sham-operation group, MI-saline group and MI-perindopril group. Left anterior descending artery was ligated to generate myocardial infarction. Perindopril (2 mg/kg body weight/day) was administered from the next day of MI. Four weeks later, left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction was estimated with echocardiography, LVSP, LVEDP and±dp/dtmax was detected with hemodynamic measurement, cardiomyocyte diameter and interstitial fibrosis infiltration were evaluated with histological methods, and myocardium osteopontin protein expression level was detected with western blot. Results ①Compared with the sham-operation group, all rats with MI developed significant systolic and diastolic dysfunction, as was indicated by decreased LVEF, LVSP and±dp/dtmax, as well as increased LVEDP. ②Rats with MI showed significantly dilated left ventricles and higher ventricular weight / body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. ③Perindopril treatment partly prevented cardiac dysfunction and left ventricular remodeling as indicated by the parameters mentioned above. ④No osteopontin protein was detected in myocardium of sham-operation rats. In rats with MI, high level osteopontin protein expression was significantly inhibited by perindopril treatment. Conclusions In rats with MI, perindopril treatment significantly prevented left ventricular remodeling and myocardium osteopontin protein expression.

Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension

Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VPBs） and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index （LVMI） using the Devereux formula and diastolic fimction by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 （r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively） and V3 （r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively） correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT （r = -0.33, P = 0.01）, Tpe in V3 （r = -0.39, P = 0.003） and Tpe/QT in V3 （r = -0.31, P = 0.02）. Tpe in V3, V5, mean Tpe and maximum Tpe with cut-offvalues of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs.

Effect of carvedilol on cardiac function and left ventricular remodeling in rats after acute myocardial infarction

Objective: To observe the effect of carvedilol injection on left ventricular function and collagen remodeling in rat with myocardial infarction. Methods: Sixty rats with a model of myocardial infarction were randomly divided into nine groups. The rats of therapeutical group were treated with carvedilol injection (2 mg/d intraperitoneal injection) and/or captopil (2 g/L drinking water) . Acute myocardial infarction ( AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin II and plasma aldosterone and left ventricle function were determined at different time. The collagen content and the ratio of type I and III collagen of noninfarcted area were also assessed. Results: Compared with AMI group, the levels of plasma and myocardium angiotensin II and plasma aldosterone in both carvedilol and captopil group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0. 05). Compared with sham group, both collagen content and the ratio of type I / III collagen of noninfarcted area increased in AMI4 and AMI8 group (P<0. 05). The hydroxyproline levels and the ratio of type I/III collagen significantly decreased after carvedilol and/or captopil treatment , compared with AMI group at 4 or 8 week (P <0. 05). Conclusion: Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular remodeling.

Effects of astragalus polysaccharides on ventricular remodeling and miRNA-21 in rats with acute myocardial infarction

Objective:To investigate the effect of Astragalus polysaccharides(APS)on myocardial remodeling and expression of miR-21 after myocardial infarction.Methods:Sixty SPF grade healthy male rats were divided into the sham operation group,the model group,astragalus polysaccharide low,medium and high dose groups and atorvastatin group randomly with 10 rats in each group.The left anterior descending coronary artery(LAD)was ligated to establish myocardial infarction model in rats,and the corresponding drug intervention was given for 4 weeks.The changes of myocardial morphology and collagen were observed by HE and Masson staining.The levels of IL-1β,IL-6,TNF-αand IL-10 were detected by ELISA.The mRNA expressions of miR-21,MMP2,TIMP-2,Col-I,and Col-III was detected by RT-PCR.The protein expressions of TLR4,MyD88 and NF-κB p65 were detected by Western blot.Results:Compared with the model group,APS could improve the pathological morphology of myocardial tissue,increase the level of IL-10 in myocardial tissue,reduce the staining area of collagen and the contents of IL-1β,IL-6 and TNF-α(P<0.05).At the same time,APS could decreased the expression of MMP2,Col-I and Col-ⅢmRNA and the ratio of MMP2/TIMP-2,and increased the expression of TIMP-2 mRNA and miR-21 significantly(P<0.05).Furthermore,APS could significantly reduce the expression of TLR4,p-NF-κB p65 and MyD88 protein in myocardial tissue of rats with myocardial infarction,and the differences were statistically significant when compared with the model group(P<0.05).Conclusion:APS can inhibit the activation of TLR4/MyD88/NF-κB signaling pathway by upregulating the expression of miR-21,which plays a therapeutic role in ventricular remodeling after acute myocardial infarction.

Effect of angiotensin receptor neprilysin inhibitor on ventricular remodeling after myocardial infarction in rats

Objective:To investigate the effect of Angiotensin Receptor Neprilysin Inhibitor(ARNI)on ventricular remodeling after AMI in rats.Methods:Sixty male SD rats were randomly divided into Control group,AMI group,AMI-valsartan group,AMI-ARNI group,15 rats in each group,ligating the left coronary anterior descending artery to establish the rat model of AMI.Valsartan group and ARNI group were treated with valsartan(34mg/kg/day)and ARNi(68mg/kg/day)for 6 weeks,the Control group and AMI group were given the same amount of normal saline.LVIDd,LVIDs,EF were measured by color doppler echocardiography before and 6 weeks after treatment.After 6 weeks,the rats were sacrificed,the hearts were weighed,then myocardial tissue Masson staining was performed to calculate the collagen volume fraction(CVF).Results:compared with the control group,LVIDs increased significantly with the reduction of EF in the AMI group,valsartan group and ARNI group(P<0.05).After 6 weeks of treatment,compared with the AMI group,LVIDd and LVIDs both reduced significantly with the increase of EF in the ARNI group(P<0.05).Compared with the control group,the left ventricular weight,right ventricular weight and atrial weight all increased significantly in the AMI group,valsartan group,and ARNI group(P<0.05);compared with the AMI group,the left ventricular weight,right ventricular weight,atrial weight and CVF reduced significantly in the valsartan group and ARNI group(P<0.05);compared with the valsartan group,the left ventricular weight and CVF further reduced in the ARNI group.(P<0.05).Conclusions:ARNI has the effect of reversing ventricular remodeling after AMI in rats,which can reduce left ventricular volume,increase myocardial contractility,and inhibit myocardial cell hypertrophy and fibrosis.

Yiqi Huoxue traditional Chinese decoction affect ventricular remodeling in rats with heart failure after myocardial infarction by regulating osteopontin expression

Objective:To investigate the mechanism of Yiqi Huoxue traditional Chinese medicine affecting the osteopontin(OPN)level in myocardial tissue and improving ventricular remodeling in heart failure rats after myocardial infarction.Methods:Forty SPF-grade SD male rats were prepared,and 10 rats were reserved as blank controls.The remaining rats were prepared by anterior descending coronary artery ligation combined with reduced diet and exhausted swimming to prepare a rat model of heart failure after myocardial infarction.The rats in the blank group and the model group were orally administered with distilled water,the Chinese medicine group was administered with Yiqi Huoxue Chinese medicine decoction,and the western medicine group was administered with captopril.After 6 weeks of treatment,small animal ultrasound was used to detect changes in ventricular structure and function in rats.Kill all the rats,and take myocardial tissue,observe the morphological changes of myocardial tissu under a light microscope.Use real-time quantitative PCR to detect the expression of OPN mRNA in rat myocardial tissue,and use immunohistochemical method to detect the expression of OPN protein in myocardial tissue.Results:Compared with the blank group,the left ventricular ejection fraction(EF),left ventricular short axis shortening fraction(FS)of the model group were significantly reduced,and the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were significantly increased,OPN mRNA and protein expression were significantly up-regulated(P<0.01),and myocardial structure disorder was seen under light microscope.Compared with the model group,the EF and FS of the Chinese medicine group and the Western medicine group were both significantly increased,the LVEDD and LVESD were significantly reduced,the expressions of OPN mRNA and protein were significantly reduced(P<0.01),and the myocardial structure was significantly improved under light microscopy.There was no statistically significant difference between the western medicine group and the traditional Chinese medicine group(P>0.05).Conclusion:Yiqi Huoxue Chinese medicine may reduce the expression of OPN in myocardial tissue,improve ventricular remodeling,improve cardiac function and prevent heart failure after myocardial infarction.

Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function

Objective: To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods: Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pacemakers were implanted to treat high-grade and third-degree atrioventricular blockage. At the time of pacemaker implantation, patients had normal cardiac functions and showed no serious heart diseases or cardiac dilatation. The durations from the implantation to follow-up were more than 5 years. The pacing rate was higher than 80%. Patients with a left ventricular ejection fraction (LVEF) < 50% and a left ventricular end-diastolic diameter (LVEDD) > 55 mm were excluded. Ventricular remodeling was defined as follows:increase of LVEDD by 10% and a reduction of LVEF by 25% for five years after implantation. Cardiac functions were evaluated according to New York Heart Association (NYHA) classification.Results:A total of 82 patients with a mean age of (66.97±13.19) years (range, 12 to 91 years old),among which 39 male and 43 female were enrolled in this study. The average duration between two assessments was 8.7 years (104.4 months). Before pacemaker implantation, the average left atrial diameter (LA), LVEDD and LVEF were 37.0 mm, 50.23 mm and 64.87%, respectively. After the implantation, these values were 39.39 mm (P=0.000163), 50.82 mm (P=0.177842) and 60.50% (P=0.000104), respectively. Four patients (4.87%) had ventricular remodeling with deteriorations of cardiac function, three of which had anterior wall myocardial infarction after implantation and one had type II diabetes. Clinical symptoms of heart failure were not found among the patients who did not exhibit ventricular remodeling. Conclusion: Through a long-period follow-up study, we found that long-term right ventricular apical pacing in patients with normal heart structure and cardiac function would not generally cause ventricular remodeling and clinical deteriorations of cardiac function. Right ventricular apical is a safe and effective site for pacing electrode wire implantation.

Hypoxia training attenuates left ventricular remodeling in rabbit with myocardial infarction

Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups： group SO （sham operated）, group MI （myocardial infarc-tion only） and group MI-HT （myocardial infarction plus hypoxia training）. Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber （having equivalent condition at an altitude of 4000 m, FiO214.9%） for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor （VEGF） in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI （130.27 ± 18.58 pg/mL,P〈 0.01） and MI-HT （181.93 ± 20.29 pg/mL,P〈 0.01） were significantly increased. Infarct size in Group MI-HT （29.67% ± 7.73%） was deceased remarkably, while its capillary density （816.0 ± 122.2/mm2） was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic （15.86 ± 1.09 mm,P〈 0.05） and end-systolic dimensions （12.10 ± 1.20 mm,P〈 0.01） significantly and im-proved left ventricular ejection fraction （54.39 ± 12.74 mm,P〈 0.05）.ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction(CODE-AAMI):Protocol for a Randomized Placebo-Controlled Trial

Background:Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction(AAMI)is an important factor in occurrence of heart failure which additionally results in poor prognosis.Therefore,the treatment of ventricular remodeling needs to be further optimized.Compound Danshen Dripping Pills(CDDP),a traditional Chinese medicine,exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.Objective:This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.Methods:This study is a multi-center,randomized,doubleblind,placebo-controlled,parallel-group clinical trial.The total of 268 patients with AAMI after primary percutaneous coronary intervention(pPCI)will be randomly assigned 1:1 to the CDDP group(n=134)and control group(n=134)with a follow-up of 48 weeks.Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction(STEMI),with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI,and the control group treated with a placebo simultaneously.The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI).The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide(NT-proBNP)level,arrhythmias,and cardiovascular events(death,cardiac arrest,or cardiopulmonary resuscitation,rehospitalization due to heart failure or angina pectoris,deterioration of cardiac function,and stroke).Investigators and patients are both blinded to the allocated treatment.Discussion:This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI.Patients in the CDDP group will be compared with those in the control group.If certified to be effective,CDDP treatment in AAMI will probably be advised on a larger scale.(Trial registration No.NCT05000411)