G-MPI测定心肌灌注缺损区占比与心肌梗死介入术后左心功能的关系及预后预测价值

目的分析静息门控心肌灌注SPECT显像(G-MPI)测定心肌灌注缺损区占比与急性心肌梗死(AMI)介入术后左心功能的关系及预后预测价值。方法选取2019年2月—2021年2月承德市中心医院接受经皮冠状动脉介入治疗(PCI)的AMI患者82例,行静息G-MPI检查,检测术后1周、4周心肌灌注缺损区占比、左心功能指标[左室射血分数(LVEF)、左室舒张末期容量(LVEDV)、左室收缩末期容量(LVESV)]水平,并依据术后6个月患者是否发生主要不良心血管事件(MACE)分为MACE组(n=21)、非MACE组(n=61)。统计比较两组一般资料、术后1周、4周心肌灌注缺损区占比、左心功能指标(LVEF、LVEDV、LVESV)水平,观察心肌灌注缺损区占比与左心功能指标相关性,探讨心肌灌注缺损区占比对AMI介入术后MACE发生的预测价值,分析AMI介入术后MACE发生有关影响因素。结果MACE组病变支数多于非MACE组,术后1周、4周心肌灌注缺损区占比、LVEDV、LVESV水平高于非MACE组,LVEF水平低于非MACE组(P<0.05);相关性分析可知,AMI患者术后1周、4周心肌灌注缺损区占比与LVEF水平呈负相关,与LVEDV、LVESV水平呈正相关(P<0.05);绘制受试者工作特征(ROC)曲线显示,术后1周、4周心肌灌注缺损区占比预测AMI介入术后MACE的曲线下面积(AUC)均较高,尤以术后4周最高,为0.836;回归分析发现,术后1周、4周心肌灌注缺损区占比为AMI介入术后MACE发生的重要影响因素(P<0.05)。结论G-MPI测定心肌灌注缺损区占比与AMI介入术后左心功能密切相关,且对患者预后MACE发生具有良好预测价值,可为临床诊治提供一定参考。

实时三维心肌超声造影评估心肌灌注缺损的实验研究

目的 探讨实时三维超声心动图 (RT 3DE)结合心肌超声造影评估心肌灌注缺损区的可行性和准确性。方法 1 3只杂种犬分别结扎左前降支 ( 6只 )或回旋支 ( 7只 ) ,经静脉注射氟烷微泡造影剂 ,应用RT 3DE显示并检测心肌灌注缺损区。心脏摘出后 ,经冠状动脉口注射伊文思蓝染料确定危险区心肌 ,以解剖方法直接测量心肌的质量作为判断标准。结果 ①冠状动脉结扎前实时三维成像测定左心室质量与离体左心室心肌实测质量差异无显著性意义 ,且密切相关 (P >0 .0 5 ,r =0 .99)。②结扎左前降支组RT 3DE测量的左心室心肌总质量与心肌标本实测总质量之间比较差异无显著性意义 (P >0 .0 5 ) ;RT 3DE检测的灌注缺损区心肌质量与心肌标本实测危险区心肌质量之间比较 ,差异也无显著性意义 (P >0 .0 5 )。③结扎回旋支组RT 3DE与心肌标本测量的左心室质量、灌注缺损区心肌质量比较 ,二者差异均无显著性意义 (均P >0 .0 5 )。④观察冠状动脉结扎后所有动物心脏 ,RT 3DE测定的左心室总质量与心肌标本比较 ,二者差异无显著性意义 ( P >0 .0 5 ) ,且存在显著相关关系 (r =0 .99)。RT 3DE测量的灌注缺损区心肌质量与心肌标本对照 ,同样差异无显著性意义 (P>0 .0 5 ) ,且二者测量的结果显著相关 (r =0 .96)。结论 实时三维超?

低管电压低浓度对比剂在一站式冠脉CTA+心肌灌注扫描中的临床应用

目的:探讨低管电压、低浓度对比剂在一站式冠脉CTA+心肌灌注(CTP)扫描中的应用价值。方法:根据不同管电压、不同浓度对比剂使用情况将实验对象分为A(管电压100kV,对比剂浓度370mg I/mL)、B(管电压100kV,对比剂浓度320mg I/mL)、C(管电压80kV,对比剂浓度370mg I/mL)、D(管电压为80kV,对比剂浓度为320mg I/mL)四组。统计四组正常心肌首过灌注中低灌注伪影的数量与集中节段,以及升主动脉、左心室前间壁、左主干、左心室等4个部位的CT值及管电压、所用对比剂量、管电流等数值;分析四组在低灌注区域、主动脉根部CT值、左心室CT值、左主干CT值和管电压、管电流、对比剂用量等方面所存在的差异。结果:4组研究对象的心肌低灌注伪影均主要分布在第7、17、13节段区域,各组的低灌注伪影数差异无统计学意义(P>0.05)。D组(低管电压、低浓度对比剂组)的升主动脉CT值、左主干CT值、左心室CT值、左心室前间壁CT值均显著高于A组(高管电压、高浓度对比剂组)、B组(高管电压、低浓度对比剂组);D组的对比剂用量、辐射剂量明显少于A组和B组;D组的升主动脉CT值、左主干CT值、左心室CT值低于C组(低管电压、高对比剂浓度组),上述差异均具有统计学意义(P<0.05)。结论:低管电压、低浓度对比剂在一站式冠脉CTA+CTP扫描中具有较高的临床应用价值。

门控心肌灌注异常与双源CT冠状动脉狭窄程度间的关系分析

目的通过分析潘生丁负荷门控心肌灌注显像（G-MPI）不同灌注异常程度与双源CT冠状动脉成像（DSCTCA）冠状动脉不同狭窄程度间的关系,评价DSCTCA预测患冠心病可能性为中-高度可能性病人心肌灌注异常程度的能力。方法115例患者一个月内行潘生丁负荷MPI和DSCTCA。心肌灌注异常的程度采用半定量分析分为：轻、中、重度放射性减低及放射性缺损。DSCTCA按照国际通用目测法将冠状动脉狭窄程度分为：狭窄〈50%、50%~69%、70%~99%及闭塞性病变。分析心肌灌注减低程度与不同程度冠状动脉狭窄间的关系。以MPI为参考标准,将DSCTCA预测心肌灌注减低的冠脉狭窄程度判定界值设为≥50%或≥70%,确定该方法的诊断效能。计数资料分析采用Mantel-Haenszelχ2、Pearsonχ2检验。结果冠状动脉狭窄〈50%、50%~69%、70%~99%及闭塞性病变中心肌灌注异常比例分别为55.6%（20/36）,71%（25/35）、81%（21/26）及83%（5/6）,随着冠状动脉狭窄程度增加心肌灌注减低发生率增加（χ2=28.16,P〈0.05）。冠脉狭窄判断界值为≥50%或≥70%时,DSCTCA预测心肌灌注减低的诊断敏感性、特异性、准确性、阳性预测值、阴性预测值分别为63.21%（67/106）或30.19%（32/106）（χ2=23.21,P〈0.05）、97.07%（232/239）或99.16%（237/239）（χ2=2.83,P〉0.05）、86.67%（299/345）或77.97%（269/345）（χ2=10.87,P〈0.05）、90.54%（67/74）或94.12%（32/34）（χ2=0.39,P〉0.05）、85.61%（232/271）或76.21%（237/311）（χ2=8.18,P〈0.05）。结论随着冠状动脉狭窄程度增加心肌灌注减低缺损发生率及程度均呈增高趋势。在冠心病中、高度可能性的患者中,以冠脉狭窄界值≥70%时DSCTCA预测心肌缺血的特异性和阳性预测值较冠脉狭窄界值为≥50%为佳。

造影增强实时三维超声心动图定量评价心肌顿抑犬的心肌灌注及其局部收缩功能

目的应用造影增强实时三维超声心动图(CERT3DE)定量评价心肌顿抑犬的心肌灌注及其局部收缩功能。方法建立犬心肌顿抑模型[冠状动脉(冠脉)结扎15min再灌注30min]。分别于基础状态、冠脉结扎15min及再灌注30min时行CERT3DE,获取其RT3DE容积数据库;脱机后根据心尖长轴观八平面法勾画舒张末期左室心肌灌注缺损区体积(VPMD)和室壁运动异常区体积(VWMA)。取出心脏,用伊文思蓝和三苯基四氮唑(TTC)染色,确定危险心肌及有无梗死心肌,剥离并测量危险心肌体积(VAREVANS)。结果冠脉结扎15min时:VWMA为(13.6±2.2)ml,VPMD为(9.0±1.4)ml,差异有显著性意义(P<0.001);再灌注30min时:VWMA为(13.0±1.9)ml,而VPMD为零,差异有显著性意义(P<0.001)。CERT3DE所测VARCERT3DE[(9.0±1.4)ml]与伊文思蓝染色结果VAREVANS[(9.2±1.5)ml]差异无显著性意义(P=0.16)且两者显著相关(r=0.92);CERT3DE所测顿抑心肌体积为(13.0±1.9)ml,TTC染色证实该区心肌无明显坏死。结论CERT3DE可准确评价心肌顿抑犬的心肌灌注及其局部收缩功能,有望为临床识别及定量评价顿抑心肌提供一项有效手段。

Protective Effects of Zingiberis and Acniti Praeparatae Decoction on Myocardial IschemiaReperfusion Injury in Rats

This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde （MDA） content in the serum, superoxide dismutase （SOD） activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury

AIM： To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion （IR） injury in rabbits and probe into the mechanism. METHODS： Forty healthy flap-eared white rabbits were randomly divided into 4 groups： IR injury control group （group Ⅰ ）, shenfu injection 5 mL/kg per h group （group Ⅱ）, shenfu injection 10 mL/kg per h group （group Ⅲ） and shenfu injection 20 mL/kg per h group （group Ⅳ）. The four groups were treated with Lactated Ringer＇s solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure （MAP）, heart rate （HR）, gastric intramucosal partial pressure of carbon dioxide （PCO2）, blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 rain after reperfusion. RESULTS： The MAP, HR and gastric intramucosal pH were （70.50 ± 4.50） kPa, （165 ± 14） beats per rain, 7.032 ± 0.024 in group Ⅰ 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia （88.50 ± 9.75 kPa, 217 ± 18 beats per rain, 7.112 ± 0.035, P 〈 0.05）. The MAP, HR and gastric intramucosal pH were significantly decreased in group Ⅰ 60, 90, and 180 min after reperfusion （61.50 ± 5.25 kPa, 133 ± 31 beats per rain, 6.997 ± 0.025） compared with those before reperfusion respectively （P 〈 0.05）, whereas the values were insignificantly different in groups Ⅱ, Ⅲ or Ⅳ after reperfusion, compared with those before reperfusion, and there were no significant differences between groups Ⅱ, Ⅲ, and Ⅳ after reperfusion. CONCLUSION： Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.

The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

Role of NF-κB in protection of EPO pretreatment on neonatal rat cardiac myocytes with hypoxia/reoxygenation injury

Objective：To observe the protective effects of erythropoietin （EPO） pretreatment on cardiac myocyte with hypoxia/reoxygenation （H/R） injury and the role of NF-κBin this effects. Methods：After the H/R model of cardiac myocytes of neonatal rats was established, the cultured cardiac myocytes were divided into 4 groups, including EPO pretreatment group （ EPO 10 U/ml 24 h before H/R）, EPO pretreatment ＋ PDTC group（EPO 10 U/ml and PDTC 5 μg/ml 24 h before H/R）, PDTC group （PDTC 5 μg /ml 24 h before H/R） and eomrolgroup. Before and after the H/R, assay of LDH concentration in the culture medium, the survival rate of the myocytes tested by MTT chromatometry and the apoptosis by flow cytometry were undertaken. Activation of NF-κB was determined by EMSA before and after H/R. Results：EPO pretreatment markedly reduced the LDH concentration in the medium, elevated the survival rate of myocytes and inhibited the apoptosis after H/R. Addition of PDTC during the pretreatment abol- ished the protective effects of EPO pretreatment. NF-κB was markedly activated during EPO pretreatment and PDTCinhibited the activation. However, after H/R, the activity of NF-κB in myocytes with EPO pretreatment was significantly inhibited compared to the other myocytes. Conclusion：NF-κB is significantly activated during EPO pretreatment, but is inhibited after H/R, which is correlated with the protective effects of EPO pretreatment on cardiac myocytes with H/R. This phenomenon can be explained as the negative feedback mechanism of the activation of NF-κB.

The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H_(2)S-mediated autophagy signaling pathway

Objective To investigate the protective effects of Jiawei Danshen Decoction(加味丹参饮,JWDSD)on myocardial ischemia-reperfusion injury(MIRI)via the regulation of serum Hydrogen sulfide(H2S)and cardiac Beclin1,light Chain 3 A/B(LC3 A/B),p62,and autophagy protein5(ATG5).Methods Seventy specific pathogen free(SPF)Sprague-Dawley(SD)rats were randomly assigned to seven groups(n=10 in each group),including normal control,sham operation,MIRI model(model),ischemic preconditioning,Na HS,JWDSD,and JWDSD+CSE inhibitor(JWDSD+PPG)groups,and orally administered the indicated drugs for 14 d.Two hours after the last administration,the left anterior decreased branch of the coronary artery of each rat in model,Na HS,JWDSD,and JWDSD+PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model,and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation.Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay(ELISA).Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 m RNA expression and Western blot analysis of Beclin1,LC3 A/B,and p62 protein expression.Results(1)The serum H2S content in model group rats was significantly reduced(P<0.01),JWDSD significantly increased the serum H2S content of model group rats(P<0.01),and the CSE inhibitor(PPG)significantly reduced H2S levels in the JWDSD group rats(P<0.01).(2)Compared with the normal control group,the myocardial tissue necrosis and cell destruction occurred in the MIRI model group,and JWDSD could alleviate the myocardial tissue necrosis of model rats,but the ameliorative effect of JWDSD could be reversed by PPG.(3)Beclin1,LC3 A/B,and p62 expression levels in the heart tissues of the model group were significantly increased(P<0.001),whereas decreased by JWDSD(P<0.05,P<0.01,and P<0.001,respectively),and the inhibitory effects of JWDSD on Beclin1,LC3 A/B,and p62 expression were partially reversed by PPG(P<0.01,P<0.05,and P<0.01,respectively).(4)The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group(P<0.001).JWDSD clearly downregulated the expression levels of Beclin1 and ATG5(P<0.05 and P<0.001,respectively),which were reversed by PPG(P<0.001).Conclusion Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation,and downregulating the expression of Beclin1,LC3 A/B,p62 and ATG5,which are related to inhibiting autophagy signaling.

Effect of Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Endothelial Progenitor Cells on Myocardial Ischemia-reperfusion Injury in Mini-swine

Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About （3.54±0.90）×10^7 bone marrow mononuclear cells （MNC group, n=9） or （1.16± 1.07）× 10^7 endothelial progenitor cells （EPC group, n=7） was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control （n=7）. Echocardio- graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc- tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively （P〈0.05）. The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups （P〉0.05）. EPC decreased total infarction size more than MNC did （1.60±0.26 cm2 vs. 3.71±1.38 cm2, P〈0.05）. Undermature endothelial cells and myocytes were found under transmission electromlcroscope. Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit flbrogenesis, and differentiate into myocardial cells.

Progresses in the research of Danhong Injection against the cardial ischemia-referfusion injury

Researches in the field of the myocardial ischemia-reperfusion injury are attracting the attentions of clinicians for the treatments that protect cardiac muscle cells from being injured can not only help the patients get recovery but also keep them in health. By clearing the free radicals and reducing calcium overload of myocardial cell, treatments with Danhong Injection will help myocardial cells survive from inflammatory reactions which are triggered by ischemia reperfusion so as that endothelial function will be improved and myocardial cell apoptosis will be inhibited. In all, Danhong Injection is an ideal medicine for protecting myocardial cell against ischemia reperfusion injury.

Effect of Shenfu injection on nuclear factor-κB during myocardial ischemia/reperfusion injury in rats

Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.Methods: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n=8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-α were measured by ELISA, and the heart was harvested for determination of NF-κB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.Results: After reperfusion, NF-κB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-α were significantly increased in Group II, compared with Group I (P< 0.01), and they were markedly reduced in Group III, compared with Group II (P< 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.Conclusions: Shenfu injection inhibits NF-κB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.

Protective effects of tanshinone ⅡA derivative on myocardial ischemia/reperfusion injury in rats

Tanshinone ⅡA（TSⅡA） is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion（MIR） injury.However,the cardioprotective effects of TSⅡA as well as its clinical use were limited due to its poor water solubility.The objective of this study was to evaluate whether Tanshinone ⅡA derivative（TD）,a new water soluble compound synthesized by TSⅡA and N-Methyl-D-Glucamine,had protective effects on MIR injury and what the related mechanism was.The cardioprotective effects of TD were evaluated and compared with TSⅡA in a rat MIR model.The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase（LDH） and malondialdehyde（MDA）,decreasing expression of nuclear factor-κ-gene binding（NF-κB） and upregulating expression of heme oxygenase（HO-1）,but having no effect on the content of total superoxide dismutase（T-SOD） and m RNA expression of superoxide dismutase（SOD-1）.Thus,our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.

Effect of electroacupuncture pretreatment on the protein expression of c-fos in fastigial nucleus and lateral hypothalamus area in rats with acute myocardial ischemia-reperfusion injury

Objective:To observe the effect of electroacupuncture(EA)pretreatment on the protein expression of c-fos in fastigial nucleus(FN)and lateral hypothalamus area(LHA)in rats with acute myocardial ischemia-reperfusion injury(MIRI),and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction.Methods:Seventy Sprague-Dawley rats were randomly divided into a sham operation group,a model group,an EA-Heart Meridian group and an EA-Lung Meridian group,with 14 rats in each group;an LHA lesion plus EA-Heart Meridian group(LHA+EA-Heart Meridian group)and a FN lesion plus EA-Heart Meridian group(FN+EA-Heart Meridian group),with 7 rats in each group.Except the sham operation group,the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups.In the three groups with EA-Heart Meridian treatment,Shenmen(HT 7)and Tongli(HT 5)were selected;Taiyuan(LU 9)and Lieque(LU 7)were selected in the EA-Lung Meridian group.All the EA groups received EA stimulation prior to modeling,with 1 mA in current intensity and 2 Hz in frequency,20 min each time,once a day for a total of 7 d.The sham operation group and the model group did not receive EA stimulation.The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score.The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method.Results:Compared with the sham operation group,the ST-segment deviation,cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group(all P<0.05).Compared with the model group,the ST-segment deviation,cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group(all P<0.05).Compared with the EA-Heart Meridian group,the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group,LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group(all P<0.05);the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group(both P<0.05);the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group(both P<0.05).Conclusion:FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions,and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats

Objective： To investigate the protective effects of acuptmcture pretreatment on ischemic myocardium, the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment. Methods： Sixty-four Wistar rats were randomly divided into eight groups： control group, sham surgery group, ischemia-reperfusion group, ischemia pretreatment group, manual acupuncture pretreatment group （once a day）, electroacupuncture pretreatment group （once a day）, manual acupuncture pretreatment group （twice a day）, and electroacupuncture pretreatment group （twice a day）. The reperfusion model of rat myocardial ischemia was made. Expression of HSP70 mRNA was assayed by in situ hybridization, and cell apoptosis by TUNEL. Results： Compared with those in the control group and the sham surgery group, the apoptosis and the expression of HSP70 mRNA were increased in the ischemia-reperfusion group. Compared with those in the ischemia-reperfusion group, the cardiac muscle cell apoptosis was decreased and the HSP70 mRNA was increased in the rats treated with acupuncture pretreatment; meanwhile, acupuncture pretreatment twice a day had stronger effects than acupuncture pretreatment once a day and ischemia pretreatrnent. Conclusion： Acupuncture pretreatment can inhibit the cardiac muscle cell apoptosis, and up-regulate the expression of HSP70 mRNA in ischemia-reperfusion rats. Acupuncture pretreatment twice a day has stronger effects than pretreatment once a day.

Effect of electroacupuncture pretreatment on adenine nucleotides in myocardial tissues of rats with myocardial ischemia-reperfusion injury detected by high performance liquid chromatography(HPLC)

Objective:To observe the effect of electroacupuncture(EA)pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury(MIRI)rats,and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats.Methods:Forty SPF male Sprague-Dawley(SD)rats were randomly divided into 5 groups:a blank group,a sham operation group,a model group,an EA at Neiguan(PC 6)group and an EA at Hegu(LI 4)group,with 8 rats in each group.Rats in the blank group only received binding to the rat plate,30 min/time,once a day for 7 d;on the 7th day,rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day,rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation,for 40 min before the blood flow was restored,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day of pretreatment with EA at Neiguan(PC 6)or Hegu(LI 4)for 30 min per day(once a day for 7 d),rats in the EA at Neiguan(PC 6)group and EA at Hegu(LI 4)group were subjected to modeling and sample collection same as in the model group.The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups.Hematoxylin-eosin(HE)staining and transmission electron microscope(TEM)were used to observe the changes in myocardial pathological morphology.The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography(HPLC).Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group.Compared with the model group,the myocardial injury in the EA at Neiguan(PC 6)and the EA at Hegu(LI 4)groups was mild or hardly any.The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group(all P<0.05);compared with the sham operation group,the adenine nucleotide level of the model group was also decreased,but the difference was not statistically significant(P>0.05);compared with the model group,the adenine nucleotide level in the EA at Neiguan(PC 6)group was increased(P<0.05),and the adenine nucleotide level in the EA at Hegu(LI 4)group was significantly increased(P<0.01).The adenine nucleotide level in the EA at Hegu(LI 4)group was higher than that in the EA at Neiguan(PC 6)group,but the difference was not statistically significant(P>0.05).Compared with the EA at Neiguan(PC 6)group,the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in the EA at Hegu(LI 4)group were significantly increased(all P<0.01).Conclusion:Both EA at Neiguan(PC 6)and Hegu(LI 4)can alleviate the pathological damage to myocardium in MIRI rats,and increase the adenine nucleotide level in myocardial tissues,and thus protect MIRI rats.EA at Hegu(LI 4)has a better protective effect than Neiguan(PC 6).

Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2

To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress,short-term transverse aortic constriction(TAC)was performed in mice and then withdrawn for several days by aortic debanding,followed by subsequent myocardial exposure to ischemia/reperfusion(I/R).Following I/R injury,the myocardial infarct size and apoptosis were markedly reduced,and contractile function was significantly improved in the TAC preconditioning group compared with the control group.Mechanistically,hypertrophic preconditioning remarkably alleviated I/R-induced oxidative stress,as evidenced by the increased reduced nicotinamide adenine dinucleotide phosphate(NADPH)/nicotinamide adenine dinucleotide phosphate(NADP)ratio,increase in the reduced glutathione(GSH)/oxidized glutathione(GSSH)ratio,and reduced mitochondrial reactive oxygen species(ROS)production.Moreover,TAC preconditioning inhibited caspase-3 activation and mitigated the mitochondrial impairment by deacetylating isocitrate dehydrogenase 2(IDH2)via a sirtuin 3(SIRT3)-dependent mechanism.In addition,the expression of a genetic deacetylation mimetic IDH2 mutant(IDH2 K413R)in cardiomyocytes,which increased IDH2 enzymatic activity and decreased mitochondrial ROS production,and ameliorated I/R injury,whereas the expression of a genetic acetylation mimetic(IDH2 K413Q)in cardiomyocytes abolished these protective effects of hypertrophic preconditioning.Furthermore,both the activity and expression of the SIRT3 protein were markedly increased in preconditioned mice exposed to I/R.Treatment with an adenovirus encoding SIRT3 partially emulated the actions of hypertrophic preconditioning,whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning.The present study identifies hypertrophic preconditioning as a novel endogenous self-defensive and cardioprotective strategy for cardiac I/R injury that induces IDH2 deacetylation through a SIRT3-dependent mechanism.A therapeutic strategy targeting IDH2 may be a promising treatment for cardiac ischemic injury.