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Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts

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Chinese Medical Journal 2013年第8期126卷 1469-1479页

作者： LI Xiang-dong YANG Yue-jin CHENG Yu-tong dou ke-fei TIAN Yi MENG Xian-min Department of Evidence Based MedicineState key Laboratory ofCardiovascular Diseases Fuwai Hospital National Center forCardiovascular Diseases Chinese Academy of Medical Sciencesand Peking Union Medical College Beijing 100037 China Department otCardiologyState key Laboratory ofCardiovascular Diseases Fuwai Hospital National Center tbrCardiovascular Diseases Chinese Academy of Medical Sciencesand Peking Union Medical College Beijing I00037 China Experimental Animal CenterState key Laboratory ofCardiovascular Diseases Fuwai Hospital National Center tbrCardiovascular Diseases Chinese Academy of Medical Sciencesand Peking Union Medical College Beijing I00037 China Core LaboratoryState key Laboratory ofCardiovascular Diseases Fuwai Hospital National Center tbrCardiovascular Diseases Chinese Academy of Medical Sciencesand Peking Union Medical College Beijing I00037 China Department of Cardiology Beijing An Zhen Hospital CapitalMedical University Beijing 100029 China

Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB）（Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.

关键词： myocardial inlarction reperfusion therapy, Chinese herbal drugs cardioprotection

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Mid-ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm and sustained ventricular tachycardia： a case report and literature review

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Chinese Medical Journal 2011年第11期124卷 1754-1757页

作者： GAO Xiao-jin KANG Lian-ming ZHANG Jian dou ke-fei YUAN Jian-song YANG Yue-jin Department of Cardiology Cardiovascular Institute and FuwaiHospital Chinese Academy of Medical Sciences & Peking UnionMedical College Beijing 100037 China

The case is a 54-year-old man with hypertrophic cardiomyopathy, mid-ventricular obstruction, apical aneurysm, and recurrence sustained monomorphic ventricular tachycardia （VT）. A coronary angiogram revealed myocardial bridging located in the middle of the left anterior descending coronary artery （LAD）, and the left ventriculogram showed an hour-glass appearance of the left ventricular cavity. There was a significant pressure gradient of 60 mmHg across the mid-ventricular obliteration at rest. A successful myectomy of the inappropriate hypertrophy myocardium and excision of the apical aneurysm were performed. Pathologic analysis demonstrated fibrosis in the apical aneurysm and thickened and narrowed vessels in the adjacent area. During the follow-up of eighteen months, the patient remained clinically stable and free from arrhythmic recurrence.

关键词： hypertrophic cardiomyopathy aneurysm ventricular tachycardia

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Acute and reversible cardiomyopathy provoked by stress in a Chinese woman

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Chinese Medical Journal 2008年第23期121卷 2454-2457页

作者： KANG Lian-ming ZHANG Jian dou ke-fei XU Zhi-min GAO Xiao-jin YANG Yue-jin Department of Cardiology Cardiovascular Institute and Fuwai Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100037 China

Areversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome. This condition is characterized by a distinctive form of systolic dysfunction that predominantly affects the distal left ventricle chamber and a favourable outcome with appropriate medical therapy.

关键词： stress induced acute cardiomyopathy reversible cardiomyopathy

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Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention： a meta analysis

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Chinese Medical Journal 2013年第9期126卷 1755-1760页

作者： LI Xiang-dong YANG Yue-jin HAO Yong-chen YANG Ying ZHAO Jing-lin dou ke-fei GU Dong-feng Department of Evidence Based Medicine Department of and Cardiology Fuwai Hospital and Cardiovascular Institute Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100037 China

Background Successful revascularization of coronary artery disease, especially ST-elevation myocardial infarction （STEMI）, does not always mean optimal myocardial reperfusion in a portion of patients because of no-reflow phenomenon. We hypothesized that statins might attenuate the incidence of myocardial no-reflow when used before percutaneous coronary intervention （PCI）. The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce myocardial no-reflow after PCI. Methods We searched the MEDLINE, Cochrane, and *** databases from inception to October 2012 for clinical trials that examined statin therapy before PCI. We required that studies initiated statins before PCI and reported myocardial no-reflow. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. Results In all, 7 studies with 3086 patients met our selection criteria. The use of pre-procedural statins significantly reduced post-procedural no-reflow by 4.2% in all PCI patients （risk ratio （RR） 0.56, 95% confidence interval （CI） 0.35 to 0.90, P=0.016）, and attenuated by 5.0% in non-STEMI patients （RR 0.41, 95% CI 0.18 to 0.94, P=0.035）. This benefit was mainly observed in the early or acute intensive statin therapy populations （RR 0.43, 95% CI 0.26 to 0.71, P=0.001）. Conclusions Acute intensive statin therapy before PCI significantly reduces the hazard of post-procedural no-reflow phenomenon. The routine use of statins before PCI should be considered.

关键词： statin coronary artery disease percutaneous coronary intervention no-reflow

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Differences in symptoms and pre-hospital delay among acute myocardial infarction patients according to ST-segment elevation on electrocardiogram: an analysis of China Acute Myocardial Infarction (CAMI) registry

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Chinese Medical Journal 2019年第5期132卷 519-524页

作者： Rui Fu Chen-Xi Song ke-fei dou Jin-Gang Yang Hai-Yan Xu Xiao-Jin Gao Qian-Qian Liu Han Xu Yue-Jin Yang Department of Cardiology Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Background: Approximately 70% patients with acute myocardial infarction (AMI) presented without ST-segment elevation on electrocardiogram. Patients with non-ST segment elevation myocardial infarction (NSTEMI) often presented with atypical symptoms, which may be related to pre-hospital delay and increased risk of mortality. However, up to date few studies reported detailed symptomatology of NSTEMI, particularly among Asian patients. The objective of this study was to describe and compare symptoms and presenting characteristics of NSTEMI vs. STEMI patients. Methods: We enrolled 21,994 patients diagnosed with AMI from China Acute Myocardial Infarction (CAMI) Registry between January 2013 and September 2014. Patients were divided into 2 groups according to ST-segment elevation: ST-segment elevation (STEMI) group and NSTEMI group. We extracted data on patients' characteristics and detailed symptomatology and compared these variables between two groups. Results: Compared with patients with STEMI (N=16,315), those with NSTEMI (N=5679) were older, more often females and more often have comorbidities. Patients with NSTEMI were less likely to present with persistent chest pain (54.3% vs.71.4%), diaphoresis (48.6% vs.70.0%), radiation pain (26.4% vs.33.8%), and more likely to have chest distress (42.4% vs.38.3%) than STEMI patients (all Pkely to present with chest distress and pre-hospital patient delay compared with patients with STEMI. It is necessary for both clinicians and patients to learn more about atypical symptoms of NSTEMI in order to rapidly recognize myocardial infarction.

关键词： Non-ST segment elevation myocardial infarction Symptom assessment Time to treatment

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Assessing the association of appropriateness of coronary revascularization and 1-year clinical outcomes for patients with stable coronary artery disease in China

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Chinese Medical Journal 2020年第1期133卷 1-8页

作者： Shen Lin Heng Zhang Chen-fei Rao Si-Peng Chen Shu-Bin Qiao Hong-Bing Yan ke-fei dou Yong-Jian Wu Yi-Da Tang Xin-Chun Yang Zhu-Jun Shen Jian Liu Zhe Zheng National Clinical Research Center of Cardiovascular Diseases State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiovascular Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Information Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiology Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cardiology Peking University People's HospitalBeijing 100044China.

Background:The Chinese appropriate use criteria(AUC)for coronary revascularization was released in 2016 to improve the use of coronary *** study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease(CAD)***:We conducted a prospective,multi-center cohort study of stable CAD patients with coronary lesion stenosis≥50%.After the classification of appropriateness based on Chinese AUC,patients were categorized into the coronary revascularization group or the medical therapy group based on treatment *** primary outcome was a composite of death,myocardial infarction,stroke,repeated revascularization,and ischemic symptoms with hospital ***:From August 2016 to August 2017,6085 patients were consecutively *** revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events(MACCEs;hazard ratio[HR]:0.62;95%confidence interval[CI]:0.45-0.86;P=0.004)than medical therapy in patients with appropriate indications(n=1617).No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications(n=2658,HR:0.81;95%CI:0.52-1.25;P=0.338)and inappropriate indications(n=1810,HR:0.80;95%CI:0.51-1.23;P=0.308).Conclusions:In patients with appropriate indications according to Chinese AUC,coronary revascularization was associated with significantly lower risk of MACCEs at 1 *** benefit was found in coronary revascularization in patients with inappropriate *** findings provide evidence for using Chinese AUC to guide clinical decision-making.

关键词： Stable coronary artery disease Appropriate use criteria Coronary revascularization

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Mis-estimation of coronary lesions and rectification by SYNTAX score feedback for coronary revascularization appropriateness

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Chinese Medical Journal 2020年第11期133卷 1276-1284页

作者： Shen Lin Heng Zhang Si-Peng Chen Chen-fei Rao Fan Wu Fa-Jun Zhou Yun Wang Hong-Bing Yan ke-fei dou Yong-Jian Wu Yi-Da Tang Li-Hua Xie Chang-Dong Guan Bo Xu Zhe Zheng National Clinical Research Center of Cardiovascular Diseases State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100032China Department of Cardiovascular Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100032China Department of Information Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100032China Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100032China Department of Biostatistics Harvard T.H.Chan School of Public HealthBostonMAUSA Center for Outcomes Research and Evaluation Yale-New Haven HealthNew HavenCTUSA.

Background::Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate *** Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score is a comprehensive system to evaluate the complexity of the overall *** hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease(CAD).Methods::In this single-center,historical control study,patients with stable CAD with coronary lesion stenosis≥50%were consecutively *** the control period,SYNTAX scores were calculated by treating *** the intervention period,SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid *** primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary ***::A total of 3245 patients were enrolled and assigned to the control group(08/2016-03/2017,n=1525)or the intervention group(03/2017-09/2017,n=1720).For SYNTAX score tertiles,17.9%patients were overestimated and 4.3%were underestimated by cardiologists in the control *** adjustment,inappropriate revascularization significantly decreased in the intervention group compared with the control group(adjusted odds ratio[OR]:0.83;95%confidence interval[CI]:0.73-0.95;P=0.007).Both inappropriate percutaneous coronary intervention(adjusted OR:0.82;95%CI:0.74-0.92;P<0.001)and percutaneous coronary intervention utilization(adjusted OR:0.88;95%CI:0.79-0.98;P=0.016)decreased significantly in the intervention *** was no significant difference in 1-year adverse cardiac events between the control group and the intervention ***::Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in sta

关键词： Real-time SYNTAX score Coronary revascularization Appropriate use criteria Quality improvement

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A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

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Chinese Medical Journal 2019年第2期132卷 127-134页

作者： Peng Fan Chao-Xia Lu Xue-Qi Dong Di Zhu Kun-Qi Yang ke-Qiang Liu Di Zhang Ying Zhang Xu Meng Hui-Qiong Tan Li-Tian YU ke-fei dou Ya-Xin Liu Xue Zhang Xian-Liang Zhou Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Emergency and Cdtical Care Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) *** involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and *** with genotype, it helps us precisely diagnose and treat for ***:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA *** were analyzed based on clinical characteristics associated with ***:A splicing mutation (c.735+1G>T) in DES was detected in the proband.A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 *** affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular *** were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was ***:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in *** studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

关键词： Desminopathy Cardiomyopathy Desmin gene Splicing mutation

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Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts

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Chinese Medical Journal 2007年第16期120卷 1416-1425页

作者： QIAN Hai-yan YANG Yue-jin HUANG Ji GAO Run-lin dou ke-fei YANG Guo-sheng LI Jian-jun SHEN Rui HE Zuo-xiang LU Min-jie ZHAO Shi-hua Department of Cardiology Fuwai Hospital and Cardiovascular Institute Peking Union Medical-College and Chinese Academy of Medical Sciences Beijing 100037 China Department of Nuclear Medicine Fuwai Hospital and Cardiovascular Institute Peking Union Medical-College and Chinese Academy of Medical Sciences Beijing 100037 China Department of Radiology Fuwai Hospital and Cardiovascular Institute Peking Union Medical-College and Chinese Academy of Medical Sciences Beijing 100037 China Department of Cardiology Renmin Hospital of Wuhan University Wuhan 430063 China

Background Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo （TXL） treatment around the transplantation of mesenchymal stem cells （MSCs） can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction （AMI） and reperfusion. Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group （n=7）; group 2, administration of low-close TXL alone from the 3rd day prior to AMI to the 4th day post transplantation （n=-7）; group 3, MSCs alone （n=-7） and group 4, TXL ＋ MSCs （n=7）. AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs （3×10^7 cells/animal） were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline （1 week after transplantation） and endpoint （6 weeks after transplantation） by single photon emission computed tomography （SPECT） and magnetic resonance imaging （MRI）. Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. Results At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone （P〈0.0001）; the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone （P〈0.0001） and the peri-infarct zone （P〈0.0001）. MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and t

关键词： mesenchymal stem cells acute myocardial infarction transplantation Tongxinluo

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Clinical and Angiographic Predictors of Major Side Branch Occlusion after Main Vessel Stenting in Coronary Bifurcation Lesions

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Chinese Medical Journal 2015年第11期128卷 1471-1478页

作者： Dong Zhang Bo Xu Dong Yin Yi-Ping Li Yuan He Shi-Jie You Shu-Bin Qiao Yong-Jian Wu Hong-Bing Yan Yue-Jin Yang Run-Lin Gao ke-fei dou Department of Cardiology State Key Laboratory of Cardiovascular Disease Cardiovascular Institute Fuwai Hospital and National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Background： Major side branch （SB） occlusion is one of the most serious complications during percutaneous coronary intervention （PCI） for bifurcation lesions. We aimed to characterize the incidence and predictors of major SB occlusion during coronary bifurcation intervention. Methods： We selected consecutive patients undergoing PCI （using one stent or provisional two stent strategy） for bifurcation lesions with major SB. All clinical characteristics, coronary angiography findings, PCI procedural factors and quantitative coronary angiographic analysis data were collected. Multivariate logistic regression analysis was performed to identify independent predictors of SB occlusion. SB occlusion after main vessel （MV） stenting was defined as no blood flow or any thrombolysis in myocardial infarction （TIMI） flow grade decrease in SB after MV stenting. Results： Among all 652 bifurcation lesions, 32 （4.91%） SBs occluded. No blood flow occurred in 18 lesions and TIMI flow grade decreasing occurred in 14 lesions. In multivariate analysis, diameter ratio between MV/SB （odds ratio [OR]： 7.71,95% confidence interval [C/]： 1.53-38.85, P = 0.01）, bifurcation angle （OR： 1.03, 95% CI： 1.02-1.05, P 〈 0.01）, diameter stenosis of SB before MV stenting （OR： 1.05, 95% CI： 1.03-1.07, P〈 0.01）, TIMI flow grade of SB before MV stenting （OR： 3.59, 95% CI： 1.48-8.72, P〈 0.01） and left ventricular eject fraction （LVEF）（OR： 1.06, 95% Cl： 1.02-1.11, P 〈 0.01） were independent predictors of SB occlusion. Conclusions： Among clinical and angiographic findings, diameter ratio between MV/SB, bifurcation angle, diameter stenosis of SB before MV stenting, TIMI flow grade of SB before MV stenting and LVEF were predictive of major SB occlusion after MV stenting.

关键词： Coronary Bifurcation Lesions Major Side Branch Occlusion Percutaneous Coronary Intervention

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