Clinical Study on Preventing and Treating Left Ventricle Remodeling after Acute Myocardial Infarction with Integrative Chinese and Western Medicine

Objective: To explore the clinical efficacy of Xuefu Zhuyu (血府逐瘀, XFZY) oral liquid combined with western medicine (WM) in reversing left ventricle remodeling (LVR) after acute myocardial infarction (AMI) in patients and its therapeutic mechanism. Methods: Sixty patients conforming to criteria were divided into the treated group and WM control group with randomly stratified method. Thirty cases were assigned to each group, they were given XFZY + WM + general treatment and WM + general treatment respectively. Color Doppler ultrasonography was used to study the changes of LVR before and after treatment. Results: In both groups, before and after treatment the P value of such parameters as the changes of their left diastolic volume (LDV), left systolic volume (LSV), left ventricle ejection fraction (EF) was <0.05, suggesting that the difference of various parameters was significantly different; but when compared with the results of the 12th week after medications, the change of LDV, LSV, EF showed that the LDV, LSV of the treated group were lower than that of the control group, the EF of the treated group was higher than that of the control group, and the P value of various groups was all <0.05, suggesting that the different data of various groups showed significant difference. Conclusion: Conventional WM treatment and XFZY combined with WM could both, in treating AMI, effectively reverse the patients' LVR; yet the use of integrative Chinese and western medicine on reversing patients LVR showed even better results than that of simple WM treatment.

Mechanisms of improvement of left ventricle remodeling by transplanting two kinds of autologous bone marrow stem cells in pigs

Background The necrosis of a large number of myocardial cells after acute myocardial infarction （AMI） results in a decrease of cardiac function and ventricle remodeling. Stem cell transplantation could improve cardiac function after AMI, but the involving mechanisms have not been completely understood. The present study aimed to investigate the effects of transplantation of autologous bone marrow mononuclear cells （BM-MNC） and mesenchymal stem cells （MSCs） via the coronary artery on the ventricle remodeling after AMI as well as the mechanisms of the effects of transplantation of different stem cells on ventricle remodeling. Methods A total of 36 male pigs were enrolled in this study, which were divided into 4 groups： control group, simple infarct model group, BM-MNC transplantation group, and MSCs transplantation group. At 90 minutes when a miniature porcine model with AMI was established, transplantation of autologous BM-MNC （（4.7±1.7）×10^7） and MSCs （（6.2±1.6）×10^5） was performed in the coronary artery via a catheter. Ultrasound, electron microscope, immunohistochemical examination and real time reverse transcriptase-pelymerase chain reaction were used respectively to observe cardiac functions, counts of blood vessels of cardiac muscle, cardiac muscle nuclear factor （NF）-κB, myocardial cell apoptosis, and the expression of the mRNA of vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） in cardiac muscles. Multivariate Logistic regression was used to analyze the correlation factors of left ventricular end-diastolic diameter （EDD）. Results The number of blood vessels in the infarct zone and around its border in the BM-MNC transplantation group was more than those in the infarct model group and MSCs group （P=0.0001） and there was less myocardial cell apoptosis in the stem cell transplantation group than that in the infarct model group （all P 〈0.01）. The positive rate of NF-κB in the stem cell transplantation group was lower than that in the infarct model group （P=0.001）. The gene expression of VEGF in the infarct border zone of the BM-MNC group was higher than that in the MSCs group （P=0.0001）. The gene expression of bFGF in the infarct border zone in the MSCs transplantation group was higher than that in the infarct model group and the BM-MNC group （P=-0.0001）. Left ventricular ejection fraction was inversely proportional to the apoptotic rate of myocardial cells and cardiac muscle NF-κB but positively correlated with the number of blood vessels and the expression of VEGF and bFGF in the infarct zone and infarct border zone. The Multivariate Logistic regression analysis on the factors influencing the left ventricular end-diastolic diameter after stem cell transplantation showed that the expression of VEGF mRNA in the cardiac muscles in the infarct zone, the number of apoptotic myocardial cells and the expression of NF-κB in the infarct border zone were independent factors for predicting the inhibitory effect on the dilation of left ventricular EDD after stem cell transplantation. Conclusions Transplantation of autologous BM-MNC and MSCs in pigs can improve the condition of left ventricular remodeling and recover the cardiac functions after AMI. The improvement of cardiac functions is related to the increase of blood vessels, the increased expression of VEGF and bFGF, the reduction of myocardial cell apoptosis, and the decrease of NF-κB level in cardiac muscle tissues after stem cell transplantation.

The Relation of Ventricle Remodeling and Brain Natriuretic Peptide in Patients After Acute Myocardial Infarction

Objectives To study the relationship between plasma BNP and cardiac structural, functional changes after AMI, and to evaluate the application of plasma BNP determination in predicting the early phase of ventricle remodeling after AMI. Methods AMI group included 37 patients, all patient underwent strict medical treatment; 32 healthy individuals were enrolled as controls. Plasma BNP was determinated by immunofluorescence. Echocardiograrn examination was used to determinate LVEF, VE , VA , VE/ VA , LVEDd, LVEDV ; All patients underwent the examinations at 72 h, 30 days and 90 days after AMI occurred, respectively, and were compared with healthy controls. Results In comparing to controls, Plasma BNP in AMI 72 h, 30 days and 90 days elevated significantly. LVEDd and LVEDV were increased significantly in all 3 phases of AMI, and EF, VE/ Va were significantly lower than in controls. Correlation analysis revealed that plasma BNP level in 72 h after AMI was positively correlated to LVEDd, LVEDV, and was positively correlated to EF, VE/ VA in 30 days and 90 days after AMI. Conclusions Plasma BNP level in 72 h after AMI is a powerful index to predict left ventricle remodeling and ventricle function as plasm BNP level is positively correlated to ventricle remodeling; lowering the plasm BNP level might be used as an end point for treatment of heart failure. （ S Chin J Cardiol 2009 ; 10（4） ： 208 -211）

Magnolol attenuates right ventricular hypertrophy and fibrosis in hypoxia-induced pulmonary arterial hypertensive rats through inhibition of the JAK2/STAT3 signaling pathway

OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound isolated from Magnolia officinalis.It possesses multiple pharmacological activities,such as anti-oxidation and anti-inflammation.This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH.METHODS①Male SD rats(220 g)were randomly divided into 5 groups(n=10):the normoxia group,the hypoxia group,the hypoxia plus Magnolol(10 and 20 mg·kg^(-1)·d-1)group,and the vehicle group.Rats in the normoxia group were kept in a normoxia environment for 4 weeks,while rats in the hypoxia group were kept in a hypoxic chamber(10%O2).The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg^(-1)(ip)once a day for 4 weeks.At the end of 4 weeks,the heart function was assessed by Doppler echocardiography,and then the rats were anesthetized with sodium pentobarbital(30 mg·kg^(-1),ip).The RVSP was measured by the right heart catheterization method.The heart tissues were collected and dissected to calculate the index of RV remodeling(RV/LV+IVS,RV/tibial length,or RV/body weight).Part of the RV samples was fixed with 4%paraformaldehyde for morphological analysis,while other samples were frozen at-80℃for molecular studies(measurements of ANP,BNP,α-SMA,and collagenⅠ/ⅢmRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels).②To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis,H9c2 or cardiac fibroblasts were divided into 7 groups:the control group,cells were cultured under normal conditions;the hypoxia group,cells were cultured under hypoxic condition(3%O2);the hypoxia plus magnolol 10 mg·kg^(-1) group,magnolol10μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg^(-1) group,magnolol 20μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group,TG-101348(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group,JSI-124(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group,an equal volume of vehicle(DMSO)was added to the culture medium before the hypoxia treatment.At the end of the experiments,the cells were collected for morphological and molecular analysis.RESULTS In vivo,male Sprang-Daley rats were exposed to 10%O2 for 4 weeks to establish an RV remodeling model,which showed hypertrophic and fibrotic features(increases of RV remodeling index,cellular size,hypertrophic and fibrotic marker expression),accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol.In vitro,the cultured H9c2 cells or cardiac fibroblasts were exposed to 3%O2 for 48 h to induce hypertrophy or fibrosis,which showed hypertrophic(increases in cellular size as well as the expression of ANP and BNP)or fibrotic features(increases in the expression of collagenⅠ,collagenⅢandα-SMA).Administration of magnolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.

Effects of atorvastatin on cardiovascular remodeling in 2-kindey and 1-clip hypertensive rats

Background Nowadays, the studies mainly focus on the function of decreasing the inflammatory factor and improving the functions of endothelium, but the Methods The 2-kindey, 1-clip hypertensive rats effects of statins on ventricular remodeling are rarely studied. （2K1C, Goldblatt） were prepared with Sprague-Dawley （SD） rat. SD rats were randomly divided into three groups： control rats, hypertensive rats and hypertensive rats treated with atorvastatin （2 mg·kg^-1·d^-1）. After 6 weeks, systolic blood pressure （SBP） was measured using the tail-cuff method. The plasma concentration of angiotensin Ⅱ and renin activity were determined by radioimmunoassay. The heart weight, the ratio of left ventricular weight and body weight was calculated. Results The plasma concentration of angiotensin Ⅱ （106.4±7.8） ng/L and renin activity （20.6±2.4） ng/L were significantly increaed in hypertensive rats compared with normal rats [ （72.3±5.4） ng/L and （12.5±3.7） ng/L] （P 〈 0.01）. The heart weight （1.46 ± 0.09）g, the ratio 3.54±0.19 （ × 10^-3） of left ventricular weight and body weight in hypertensive rats were obviously higher than that in normal rats [（0.98±0.07）g and （2.28 ± 0.06） × 10^-3] （P 〈 0.01）. After treatment with atorvastatin, the plasma concentration of angiotensin Ⅱ （68.3 ± 6.9） ng/L and renin activity（8.7 ± 2.3 ）ng/L, heart weight（1.05± 0.04）g, the ratio 2.36 ± 0.07 （×10^-3） above were decreased significantly, there were no difference between the group of hypertensive rats and the normal. Conclusions Atorvastatin can decrease the ratio of left ventricular weight and body weight and has the effects on cardiovascular remodeling in hypertensive rats.

Percutaneous Ventricular Restoration Therapy Using the Parachute Device in Chinese Patients with Ischemic Heart Failure： Three-Month Primary End-point Results of PARACHUTE China Study

Background： The primary cause of ischemic heart failure （HF） is myocardial infarction （MI） resulting in left ventricle （LV） wall motion abnormality secondary to ventricular remodeling. A prospective, nonrandomized study conducted in China was designed to assess safety and efficacy of the percutaneous ventricular restoration therapy using Parachute device （CardioKinetix, lnc., CA, USA） in ischemic HF patients as a result of LV remodeling after anterior wall M1. Methods： Thirty-one patients with New York Heart Association （NYHA） Class I1, I11 ischemic HF, ejection traction between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularized were enrolled from seven sites in China from October to December 2014. The Parachute device was implanted through femoral artery. All patients received low-dose aspirin and anticoagulation with warfarin tbr at least 12 months postdevice implantation. The primary end-point was the assessment of efficacy as measured by the reduction in LV end-systolic volume index （LVESVI） against baseline LVESVI at 3 months postdevice implantation, determined by the echocardiography and measured by echocardiography core laboratory. Quality of life was assessed using EQ-SD and visual analog scale （VAS）. For quantitative data comparison, paired t-test （normality data） and signed-rank test （abnormality data） were used： application of signed-rank test was tbr the ranked data comparison. Results： A change in LVESVI as measured by echocardiography from the preimplant baseline to 3-month postdevice implantation revealed a statistically significant reduction from 77.5 ~ 20.0 ml/m-＇ to 53,1 ~ 17.0 ml/m-＂ （P 〈 0.0001 ）, The trial met its primary end-point. Of the 31 patients, the procedural success was 96.8%. Overall, NYHA HF class assessment results showed an improvement of more than halfa class at 3 months （P 〈 0.001 ）. Quality of life assessed by the VAS value increased 11.5 points （P 〈 0.01 ）, demonstrating improvement at 3 months.Conclusion： The favorable outcomes observed in the high-risk patients provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for ischemic HF patients. Trial Registration： ClinicalTrials.gov, NCT02240940; https：// clinicaltrials.gov/ct2/show/NCT02240940.

Effects of Surgical Ventricular Restoration on Left Ventricular Shape, Size, and Function for Left Ventricular Anterior Aneurysm

Background： Surgical ventricular restoration （SVR） has been performed to treat left ventricular （LV） aneurysm. However, there is limited analysis of changes in LV shape. This study aimed to evaluate the changes in LV shape induced by SVR and the effects of SVR on LV size and function for LV aneurysm. Methods： Between April 2006 and March 2015, 18 patients with dyskinetic （dyskinetic group） and 12 patients with akinetic （akinetic group） postinfarction LV anterior aneurysm receiving SVR with the Dor procedure at Chinese People＇s Liberation Army General Hospital were enrolled in this study. A retrospective analysis was carried out using data from the echocardiography database. LV shape was analyzed by calculating the apical conicity index （ACI）. LV end-diastolic volume index, end-systolic volume index, and ejection fraction （EF） were measured. One-way analysis of variance was used to compare means at different time points within each group. Results： Within one week after SVR, LV shape became more conical in the two groups （ACI decreased from 0.84 ± 0.13 to 0.69 ± 0.11 [t = 5.155, P = 0.000] in dyskinetic group and from 0.73 ± 0.07 to 0.60 ± 0.11 [t = 2.701, P = 0.026] in akinetic group; LV volumes were decreased significantly and became closer to normal values and EF was improved significantly in the two groups）. On follow-up at least one year, LV shape remained unchanged in dyskinetic group （ACI increased from 0.69 ± 0.11 to 0.74 ± 0.12, t = - 1.109, P = 0.294）, but became more spherical in akinetic group （ACI significantly increased from 0.60 ± 0.11 to 0.75 ±0.11, t = -I .880, P = 0.047）; LV volumes remained unchanged in dyskinetic group, but increased significantly in akinetic group and EF remained unchanged in the two groups. Conclusions： SVR could reshape LV to a more conical shape and a more normal size and improve LV function significantly early after the procedure in patients with dyskinetic or akinetic postinfarction LV anterior aneurysm. However, LV tends to be more spherical and enlarged in the akinetic group on at least 1-year follow-up.