Role of β-Adrenergic Signal Transduction Pathway on Myocardial Ischemic Preconditioning of Rats

To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .

Plasma hemoglobin concentration was related to estimated glomerular filtration rate in elderly patients with ischemic cardiomyopathy

Objectives To study the relationship between plasma hemoglobin concentration and estimated glomerular filtration rate （eGFR） in elderly patients with ischemic cardiomyopathy （ICM）.Methods Clinical data of patients with coronary heart disease who were discharged from The First Affiliated Hospital,Chongqing Medical University between 2005 and 2007 were analyzed retrospectively. Echocardiography results,plasma hemoglobin and creatinine concentration were abstracted from the medical records.The study included 235 Chinese Hart patients with age 60 years and older with angiography confirmed coronary heart disease,silent myocardial ischemia or angina pectoris,of whom 154 had ICM defined as left ventricular end-diastolic diameter （LVDd）,male≥56 mm,female≥51 mm （63. 51±7.70 mm） measured by M-mode echocardiography.The differences in plasma hemoglobin concentration were analyzed retrospec- tively between patients with and without ICM,and between patients with an eGFR【60 ml·min-1·1.73m-2 and those with an eGFR≥60 ml·min-1·1.73m-2.Results There were no significant differences in plasma hemoglobin concentration and eGFR between ICM and non-ICM group (118.49±20.52 g·L-1 vs.115.80±23.32 g·L-1 and 75.13±24.21 ml·min-1·1.73m-2 vs.79.09±28.41 ml·min- 1·1.73m-2,respectively,both P】0.05).However,in both ICM and non-ICM groups,plasma hemoglobin concentration was lower in those with an eGFR【60 ml·min-1·1.73m-2 compared with compared with those with an eGFR≥60 ml·min-1·1.73m-2 group (112. 29±18.61 g·L-1 vs.119.92±20.74L-1,P【0.05);plasma hemoglobin concentration was related positively to eGFR.Conclusions There were no significant changes in plasma hemoglobin concentration and eGFR;however,plasma hemoglobin concentration was related to eGFR significantly positively in elderly patients with ICM due to coronary heart

Increasing Uric Acid Concentration in Elderly With Ischemic Cardiomyopathy

Objectives Plasma uric acid （UA） concentration was suspected to elevate in elderly with ischemic cardiomyopathy （ICM）. Methods We analyzed the data of 235 elderly aged 60 years and older with coronary heart disease： silent myocardial ischemia or angina pectoris confirmed by angiography. Among these patients, 154 had ICM defined as left ventricular end-diastolic diameter （LVDd） male 〉 55 mm, female 〉 50 mm （mean. 63.51 ± 7.70 mm） measured by echocardiography. Difference in UA was analyzed between patients with and without ICM. Results There was significant increase of UA in ICM compared with non-ICM （432.82 ± 143.05 umol/L vs 361. 06 ± 137.35 umol/L, P 〈 0. 05 ） ; and UA was positively related to LVDd （ r = 0. 25, P 〈 0. 05 ）. Conclusions There was significant increase of UA in elderly with ICM due to longterm silent myocardial ischemia and angina pectoris. Moreover, UA was positively related to LVDd. （ S Chin J Cardiol 2009; 10（4） ： 212 -215）

Impact of hypoglycemic agents on myocardial ischemic preconditioning

Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C(PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.

Xuefu Zhuyu Oral Liquid (血府逐瘀口服液) Prevents Apoptosis of Ischemic Myocardium Cells in Rats by Regulating SIRT1 and Its Pathway-Related Genes

Objective:To observe the changes of ischemic myocardial cells apoptosis in rats following intervention with Xuefu Zhuyu Oral Liquid(血府逐瘀口服液,XFZY),as well as changes of protein expression of silent information regulator 1(SIRT1)and SIRT1 pathway-related genes.Methods:H9c2 rat myocardial cells were divided into 6 groups:control group,oxygen glucose deprivation(OGD)group,SIRT1 siRNA group,OGD+SIRT1 siRNA group,OGD+XFZY group,and OGD+SIRT1 siRNA+XFZY group.Quantitative fluorescent polymerase chain reaction(PCR)and Western blot were used to detect the concentration variations of SIRT1 and its pathway-related genes and corresponding protein expression after XFZY intervention and SIRT1 transfection.Results:Compared with the control group,the mRNA and protein expressions of SIRT1 were decreased obviously,while the mRNA and protein levels of P53,forkhead box protein O1(FoxO1),FoxO3,FoxO4 and nuclear factor kappa B(NF-κB)were increased in the OGD group,SIRT1 siRNA group,and OGD+SIRT1 siRNA group(P<0.01).Compared with the OGD group and OGD+SIRT1 siRNA group,the treatment of XFZY inhibited the decline in SIRT1 mRNA and protein expressions(P<0.01),and down-regulated the mRNA and protein levels of P53,FoxO1,FoxO3,FoxO4 and NF-κB,respectively(P<0.05 or P<0.01).Conclusion:XFZY could prevent myocardial cells apoptosis probably by increasing the mRNA and protein expressions of SIRT1 and inhibiting the mRNA and protein expressions of P53,NF-κB,FoxO1,FoxO3 and FoxO4.

Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies

Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular(approximately 10% of tissue volume), interstitium(approximately 15%) and intracellular(approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types Ⅰ/Ⅲ collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis(e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy(hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging(MRI) has the ability to characterize tissue proton relaxation times(T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI(DE-MRI) and multi-detector computed tomography(DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies.

Ischemic heart disease,factor predisposing to Barrett's adenocarcinoma: A case control study

AIM:To define the significance of ischemic heart disease(IHD)(stable angina to infarction) co-existance in Barrett esophagus(BE) patients and patients with esophageal adenocarcinoma(AdE).METHODS: All BE/AdE patients in Blackpool-Wyre-Fylde area and Trikala prefecture identified from medical records. Patient clinical details were obtained from hospital and General Practitioner records. Additional information was gathered from validated questionnaire.RESULTS: Forty(33%) AdE and 83(19%) BE patients had IHD(P = 0.002). Eighteen(15%) AdE and 34(8%) BE patients had suffered a myocardial infarction(P = 0.03). Three(3%) AdE and 7(2%) BE patients had severe heart failure(P = 0.82). Thirty-nine(47%) BE with IHD and 8(20%) AdE patients with IHD consumed aspirin daily(P = 0.004). Seventh-seven(93%) BE patients with IHD and 36(90%) AdE patients with IHD were on statins(P = 0.86). Logistic regression analysis: AdE was more frequent in the elderly,with long termreflux,long BE and concurrent IHD(odds ratio: 2.086,P = 0.001) not consuming statins. Eighteen(22%) BE patients with IHD [16(84%) with myocardial infarction] vs 33(10%) without IHD died from non-neoplastic causes within 24 mo from BE diagnosis(P = 0.005). CONCLUSION: IHD is more prevalent in AdE than BE patients. Increased prevalence of AdE is related with the presence of myocardial infarction but not severe heart failure,possibly because patients with BE and se-vere IHD have low life expectancy.

1990—2021年中国归因于饮食因素的缺血性心脏病疾病负担变化趋势及预测研究

背景缺血性心脏病(IHD)是导致中国居民疾病负担的第二大原因,饮食因素干预被认为是减少疾病负担有效及可行的措施。目的分析1990—2021年中国归因于饮食因素的IHD疾病负担变化及未来变化趋势,以期为中国IHD的饮食防治提供参考。方法提取2021年全球疾病负担(GBD 2021)数据库中1990—2021年中国、全球、不同社会人口指数(SDI)地区的归因于饮食因素的IHD疾病负担相关数据,应用Joinpoint模型计算年度变化百分比(APC)及平均年度变化百分比(AAPC),分析1990—2021年中国、全球、不同SDI地区归因于饮食因素的IHD疾病负担,中国不同性别、年龄人群归因于饮食因素的IHD疾病负担以及归因于不同类型饮食因素的IHD疾病负担。利用贝叶斯年龄时期队列(BAPC)模型预测2022—2031年中国归因于饮食因素的IHD标化死亡率、标化伤残调整寿命年(DALY)率变化趋势。结果2021年中国归因于饮食因素的IHD标化死亡率为44.26/10万、标化DALY率为820.87/10万,与全球水平接近,高于高SDI地区,低于其余4类SDI地区。1990—2021年中国归因于饮食因素的IHD标化死亡率(AAPC=-0.17%,P<0.001)、标化DALY率(AAPC=-0.50%,P<0.001)与全球及五类SDI地区一致,均呈现下降趋势,全球下降幅度明显高于中国,高SDI地区下降速度最快。1990年与2021年中国男性归因于饮食因素的IHD疾病负担均高于女性;1990—2021年中国男性归因于饮食因素的IHD标化死亡率(AAPC=0.25%,P<0.001)呈上升趋势,女性标化死亡率(AAPC=-0.71%,P<0.001)、标化DALY率(AAPC=-1.23%,P<0.001)均呈下降趋势。1990与2021年中国归因于饮食因素的IHD疾病负担随着年龄增长呈上升趋势,≥70岁人群的死亡率、DALY率最高;1990—2021年50~69岁人群死亡率、DALY率呈下降趋势,而15~49岁、≥70岁人群呈上升趋势(P<0.001)。1990年与2021年归因于13种饮食因素的IHD标化死亡率、标化DALY率排名前两位的饮食因素均是钠摄入过量、全谷物摄入不足;1990—2021年标化死亡率、标化DALY率上升趋势较明显的是含糖饮料摄入过量、加工肉摄入过量、红肉摄入过量。BAPC模型显示,未来10年中国归因于饮食因素的IHD标化死亡率,标化DALY率均呈下降趋势。结论1990—2021年中国归因于饮食因素的IHD标化死亡率、标化DALY率均呈下降趋势,但下降速度与高SDI地区相比差距较大,男性和老年人群负担较重,因此仍需重视IHD的饮食防控策略,加强宣传健康的膳食模式,倡导增加全谷物的摄入,减少钠盐、含糖饮料、加工肉、红肉的摄入,采取针对性措施进行有效干预以减轻其疾病负担。

Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease

Adipose tissue-deried stem cells( ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells(VECs), vascular smooth muscle cells(VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissueresident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction(AMI), ischemic cardiomyopathy(ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application.

Atypical presentation of acute and chronic coronary artery disease in diabetics

In patients with diabetes mellitus, cardiovascular disease is the principal cause of mortality and chest pain is the most frequent symptom in patients with stable and acute coronary artery disease. However, there is little knowledge concerning the pervasiveness of uncommon presentations in diabetics. The symptomatology of acute coronary syndrome, which comprises both pain and non-pain symptoms, may be affected by traditional risk factors such as age, gender, smoking, hypertension, diabetes, and dyslipidemia. Such atypical symptoms may range from silent myocardial ischemia to a wide spectrum of non-chest pain symptoms. Worldwide, few studies have highlighted this under-investigated subject, and this aspect of ischemic heart disease has also been under-evaluated in the major clinical trials. The results of these studies are highly diverse which makes definitive conclusions regarding the spectrum of atypical presentation of acute and even stable chronic coronay artery disease difficult to confirm. This may have a significant impact on the morbidity and mortality of coronary artery disease in diabetics. In this up-to-date review we will try to analyze the most recent studies on the atypical presentations in both acute and chronic ischemic heart disease which may give some emphasis to this under-investigated topic.

Non-alcoholic steatohepatitis and the risk of myocardial infarction: Apopulation-based national study

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is a systemic disease with bidirectionalrelationships with cardiovascular disease (CVD). Non-alcoholic steatohepatitis(NASH) is a more severe subtype of NAFLD. Patients with NASH exhibit moreintra and extrahepatic inflammation, procoagulant imbalances andproatherogenic lipid profiles. Whether NASH increases the risk of ischemic heartdisease is currently unclear.AIMTo investigate the relationship between acute myocardial infarction (MI) andNASH in a large cohort of subjects in the United States.METHODSWe reviewed data from a large commercial database (Explorys IBM) thataggregates electronic health records from 26 large nationwide healthcare systems.Using systemized nomenclature of clinical medical terms (SNOMED CT), weidentified adult with the diagnosis of NASH from 1999-2019. We includedpatients with the diagnosis of acute MI from 2018-2019. Comorbidities known tobe associated with NASH and MI such as obesity, diabetes mellitus,hyperlipidemia, smoking, male gender, and hypertension were collected.Univariable and multivariable analyses were performed to investigate whetherNASH is independently associated with the risk of MI.RESULTSOut of 55099280 patients, 43170 were diagnosed with NASH (0.08%) and 107000(0.194%) had a MI within 2018-2019. After adjusting for traditional risk factors,NASH conferred greater odds of MI odds ratio (OR) 1.5 [95% confidence interval(CI): 1.40-1.62]. Hyperlipidemia had the strongest association with MI OR 8.39(95%CI: 8.21-8.58) followed by hypertension OR 3.11 (95%CI: 3.05-3.17) andsmoking OR 2.83 (95%CI: 2.79-2.87). NASH had a similar association with MI asthe following traditional risk factors like age above 65 years OR 1.47 (95%CI: 1.45-1.49), male gender OR 1.53 (95%CI: 1.51-1.55) diabetes mellitus OR 1.89 (95%CI:1.86-1.91).CONCLUSIONMI appears to be a prevalent disease in NASH. Patients with NASH may needearly identification and aggressive cardiovascular risk modification.

Myocardial perfusion imaging in patients with a recent, normal exercise test

AIM: To investigate the added value of myocardial perfusion scintigraphy imaging (MPI) in consecutive patients with suspected coronary artery disease (CAD) and a recent, normal exercise electrocardiography (ECG). METHODS: This study was a retrospective analysis of consecutive patients referred for MPI during a 2-year period from 2006-2007 at one clinic. All eligible patients were suspected of suffering from CAD, and had performed a satisfactory bicycle exercise test (i.e. , peak heart rate > 85% of the expected, age-predicted maximum) within 6 mo of referral, their exercise ECG was had no signs of ischemia, there was no exercise-limiting angina, and no cardiac events occurred between the exercise test and referral. The patients subsequently underwent a standard 2-d, stress-rest exercise MPI. Ischemia was defined based on visual scoring supported by quantitative segmental analysis (i.e. , sum of stress score > 3). The results of cardiac catheterizationwere analyzed, and clinical follow up was performed by review of electronic medical files. RESULTS: A total of 56 patients fulfilled the eligibility criteria. Most patients had a low or intermediate ATPⅢ pretest risk of CAD (6 patients had a high pre-test risk). The referral exercise test showed a mean Duke score of 5 (range: 2 to 11), which translated to a low postexercise risk in 66% and intermediate risk in 34%. A total of seven patients were reported with ischemia by MPI. Three of these patients had high ATPⅢ pre-test risk scores. Six of these seven patients underwent cardiac catheterization, which showed significant stenosis in one patient with a high pre-test risk of CAD, and indeterminate lesions in three patients (two of whom had high pre-test risk scores). With MPI as a gate keeper for catheterization, no significant, epicardial stenosis was observed in any of the 50 patients (0%, 95% confidence interval 0.0 to 7.1) with low to intermediate pre-test risk of CAD and a negative exercise test. No cardiac events occurred in any patients within a median follow up period of > 1200 d. CONCLUSION: The added diagnostic value of MPI in patients with low or intermediate risk of CAD and a recent, normal exercise test is marginal.

Diagnostic accuracy of cardiac computed tomography angiography for myocardial infarction

AIM:To investigate diagnostic accuracy of high,low and mixed voltage dual energy computed tomography(DECT) for detection of prior myocardial infarction(MI).METHODS:Twenty-four consecutive patients(88% male,mean age 65 ± 11 years old) with clinically documented prior MI(】 6 mo) were prospectively recruited to undergo late phase DECT for characterization of their MI.Computed tomography(CT) examinations were performed using a dual source CT system(64-slice Definition or 128-slice Definition FLASH,Siemens Healthcare) with initial first pass and 10 min late phase image acquisitions.Using the 17-segment model,regional systolic function was analyzed using first pass CT as normal or abnormal(hypokinetic,akinetic,dyskinetic).Regions with abnormal systolic function were identified as infarct segments.Late phase DE scans were reconstructed into:140 kVp,100 kVp,mixed(120 kVp) images and iodine-only datasets.Using the same 17-segment model,each dataset was evaluated for possible(grade 2) or definite(grade 3) late phase myocardial enhancement abnormalities.Logistic regression for correlated data was used to compare reconstructions in terms of the accuracy for detecting infarct segments using late myocardial hyperenhancement scores.RESULTS:All patients reported prior history of documented myocardial infarction,with most occurring more than 5 years prior(n = 18;75% of cohort).Fiftyfive of 408(13%) segments demonstrated abnormal wall motion and were classified as infarct.The remaining 353 segments were classified as non-infarcted segments.A total of 1692 segments were analyzed for late phase enhancement abnormalities,with 91(5.5%) segments not interpretable due to artifact.Combined grades 2 and 3 compared to grade 3 only enhancement abnormalities demonstrated significantly higher sensitivity and similar specificity for detection of infarct segments for all reconstructions evaluated.Evaluation of different voltage acquisitions demonstrated the highest diagnostic performance for the 100 kVp reconstruction which had higher diagnostic accuracy(87%;95%CI:80%-90%),sensitivity(86%-93%;95%CI:54%-78%) and specificity(90%;95%CI:86%-93%) compared to the other reconstructions.For sensitivity,there were significant differences noted between 100 kVp vs 140 kVp(P【0.0005),100 kVp vs mixed(P【0.0001),and 100 kVp vs iodine only(P【0.005) using combined grade 2 and grade 3 perfusion abnormalities.For specificity,there were significant differences noted between 100 kVp vs 140 kVp(P【0.005),and 100 kVp vs mixed(P【0.01) using combined grades 2 and 3 perfusion abnormalities.CONCLUSION:Low voltage acquisition CT,100 kVp in this study,demonstrates superior diagnostic performance when compared to higher and mixed voltage acquisitions for detection of prior MI.

Acute coronary syndrome after infliximab therapy in a patient with Crohn’s disease

Infliximab is a potent anti-TNF antibody, which is used with great success in Crohn’s disease patients. Since its release in clinical practice, several adverse reactions have been observed. The interest in possible consequences of its administration is still high because of the recent introduction of the drug for the long-term maintenance therapy of refractory luminal and fistulizing Crohn’s disease. We present a case of acute coronary syndrome (non-STEMI) in a patient with corticoid resistant Crohn’s disease after his first dose of infliximab. By reviewing the scant articles that exist in the literature on this topic we made an effort to delineate the possible mechanisms of this phenomenon.

苦参碱调节RhoA-ROCK信号通路对冠心病模型大鼠Th17/Treg细胞平衡的影响

目的探讨苦参碱(Matrine)对冠心病(coronary heart disease,CHD)大鼠辅助T细胞17(helper T cell 17,Th17)/调节性T细胞(regulatory T cells,Treg)细胞平衡及Ras同源基因家族成员A(RhoA)-Rho相关的卷曲螺旋激酶(ROCK)信号通路的影响。方法建立冠心病模型,将实验大鼠分为对照组、模型组、苦参碱低剂量(50 mg·kg^(-1))组、苦参碱高剂量(200 mg·kg^(-1))组及苦参碱高剂量(200 mg·kg^(-1))+LPA组(10 mg·kg^(-1))。超声心动图进行大鼠心功能检测;酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法进行白细胞介素17(IL-17)、转化生长因子β(TGF-β)水平检测;流式细胞术检测Th17、Treg数量及Th17/Treg比值;免疫组化进行内皮型一氧化氮合酶(eNOS)、内皮素1(ET-1)蛋白表达水平检测;Masson染色进行大鼠心肌组织的病理形态变化观察;TTC染色检测各组大鼠心肌梗死情况;TUNEL染色进行心肌组织中细胞凋亡情况检测;试剂盒检测RhoA活性;Western Blot法进行半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、B细胞淋巴瘤因子2(Bcl-2)、Bcl-2相关X蛋白(Bax)、RhoA、ROCK1、ROCK2蛋白表达水平检测。结果与对照组比较,模型组心肌组织有大量蓝色胶原纤维沉积,左室舒张末期容积(left ventricular end-diastolic volume,LVEDV)、左室收缩末期容积(left ventricular end-systolic volume,LVESV)、IL-17、Th17、Th17/Treg、ET-1、心肌梗死面积、细胞凋亡率、TUNEL阳性率、Bax、Caspase-3、RhoA活性、RhoA、ROCK1、ROCK2表达水平明显升高,左室射血分数(left ventricular ejection fraction,LVEF)、左室缩短分数(left ventricular shortening fraction,LVFS)、TGF-β、Treg、eNOS、Bcl-2表达水平明显降低(P<0.05)。与模型组比较,Matrine-L组、苦参碱高剂量组心肌组织蓝色胶原纤维逐渐减少,LVEDV、LVESV、IL-17、Th17、Th17/Treg、ET-1、心肌梗死面积、细胞凋亡率、TUNEL阳性率、Bax、Caspase-3、RhoA活性、RhoA、ROCK1、ROCK2表达水平依次明显降低,LVEF、LVFS、TGF-β、Treg、eNOS、Bcl-2表达水平依次明显升高(P<0.05)。与苦参碱高剂量组比较,苦参碱高剂量+LPA组心肌组织蓝色胶原纤维增多,LVEDV、LVESV、IL-17、Th17、Th17/Treg、ET-1、心肌梗死面积、细胞凋亡率、TUNEL阳性率、Bax、Caspase-3、RhoA活性、RhoA、ROCK1、ROCK2表达水平明显升高,LVEF、LVFS、TGF-β、Treg、eNOS、Bcl-2表达水平明显降低(P<0.05)。结论苦参碱通过抑制RhoAROCK信号通路调节Th17/Treg细胞平衡,改善冠心病大鼠心肌损伤。

急性心肌梗死主动脉内球囊反搏术后发生缺血性肠病一例

1病例资料患者男性,67岁,因“胸闷7 d,再发加重10 h”于2023年2月9日入院。患者于7 d前无明显诱因出现胸闷不适,主要位于胸骨左缘,持续约10 min,伴气短,休息后症状稍缓解,期间发作数次。于10 h前上述症状再发加重,持续无缓解,遂来院就诊。既往史:高血压病史10年,最高血压170/90 mmHg,口服培哚普利治疗,血压控制尚可.

从医学影像到临床诊疗:2023年心血管磁共振进展

心血管磁共振(cardiovascular magnetic resonance, CMR)具有无创、无辐射、多参数成像的优势,能够实现对心脏形态、功能和组织学信息的“一站式”评估,在心血管疾病的精准医疗中发挥着无可替代的重要作用。2023年CMR研究取得了长足的进展:组织特征成像、心肌应变分析等技术不断推陈出新,探索更多临床适应证,并逐步完成标准化应用转化;非缺血性心脏病、缺血性心脏病等领域的CMR应用在新版指南中备受重视,且优质循证证据不断涌现,鼓励其更多地参与到心血管临床管理之中。本文将从技术和临床应用两方面系统性回顾其中代表性成果,以期为现阶段医疗实践提供实时有效的指导。

瓜蒌提取物对缺血性心肌病大鼠心肌纤维化改善作用的实验研究

目的:观察瓜蒌提取物对缺血性心肌病(ICM)大鼠心肌纤维化的改善作用,并探讨其作用机制。方法:SD大鼠36只,随机分成正常对照组、模型组、瓜蒌提取物组,每组12只。腹腔注射20%氨基甲酸乙酯(5 mg/kg)制备大鼠ICM模型,瓜蒌提取物组灌胃瓜蒌提取物溶液4 g/kg,正常对照组和模型组灌胃相同剂量生理盐水,给药4周,ELISA法检测血清心肌纤维化指标[转化生长因子(TGF)-1β、结缔组织生长因子(CTGF)、半乳糖凝集素(Gal)-3],化学发光法检测氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)],ELISA法检测炎性因子[白细胞介素(IL)-6,肿瘤、坏死因子(TNF)-α,C反应蛋白(CRP)]。光镜观察各组大鼠心肌组织病理变化。结果:模型组血清TGF-1β、CTGF、Gal-3水平均高于正常组,瓜蒌提取物组TGF-1β、CTGF、Gal-3水平均低于模型组,差异有统计学意义(P<0.05)。模型组血清SOD活性低于正常组,MDA含量高于正常组;瓜蒌提取物组SOD活性高于模型组,MDA含量低于模型组,差异有统计学意义(P<0.05)。模型组血清TNF-α、IL-6、CRP水平高于正常组,瓜蒌提取物组TNF-α、IL-6、CRP水平低于模型组,差异有统计学意义(P<0.05)。Masson染色显示,正常组大鼠心肌组织血管周围见少量均匀分布的胶原纤维。模型组大鼠心肌组织可见大量胶原纤维,且深入组织间隙,分布不均匀,形态杂乱。瓜蒌提取物组心肌组织形态基本正常。结论:瓜蒌提取物能够减轻ICM大鼠心肌纤维化程度,其作用与抗氧化、抗炎作用有关。

人造外泌体治疗心肌梗死:应用现状及前景

背景:心肌梗死是目前最严重的心血管疾病之一,现有的临床治疗方案如溶栓治疗、经皮冠状动脉介入治疗和冠状动脉旁路移植术均无法完全恢复缺血造成的心肌损伤。干细胞来源的外泌体治疗心肌梗死是近年来的研究热点,但天然来源的外泌体产量少,获取难度大、耗时长、归巢效果不佳等限制了其临床应用。在这种情况下,构建人造外泌体作为天然外泌体的替代品已成为解决上述问题的有效策略。目的:阐述人造外泌体在治疗心肌梗死中的研究现状,将其分为半人造和全人造两种设计模式,就两种模式的研究进展及存在的问题展开讨论,最后对其在未来的临床应用做出评价和展望。方法:以“人造外泌体,心肌梗死,工程化”为中文检索词,以“artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system”为英文检索词,检索PubMed和中国知网数据库的相关文献。检索时限重点为2017年1月至2022年12月,同时纳入部分经典远期文献。通过阅读文题和摘要进行初步筛选;排除重复性研究、低质量期刊及内容不相关的文献,最后纳入73篇文献进行综述。结果与结论:(1)通过半人造改造外泌体的方式,不论是靶向肽段的修饰、生物膜的杂交或是磁力物质的辅助,均改善了传统的外泌体疗法靶向性不足、驻留率低、易被网状内皮系统所清除等缺陷,提高了传统外泌体治疗心肌梗死的效率,但是这些改造策略存在修饰效率不明确、医学伦理以及生物毒性等方面的问题。(2)全人造仿生外泌体相对于外泌体的改造,其设计自由度较高,可以解决天然来源外泌体提取存储难度高、规模化生产局限等问题,然而全人造外泌体的改造策略目前仍缺少可靠的临床前数据支持与生物安全性的检测,尚未形成规模化生产所需的标准化流程,因此在应用到临床以前,作为替代天然外泌体的人造外泌体方案仍需要科研人员进行持续深入研究。