重组人生长激素对急性心肌梗死大鼠冠状动脉侧支循环的影响

目的 :探讨重组人生长激素 (rh GH)对急性心肌梗死 (AMI)大鼠冠状动脉侧支循环及血管内皮细胞生长因子 (VEGF)、成纤维细胞生长因子 (bFGF)的影响。方法 :5 0只Wistar大鼠经 10 %戊巴比妥钠麻醉后开胸 ,剪开心包腔 ,经左冠状动脉前降支结扎术致其发生AMI ,术后 2 4h存活者 37只被随机分为治疗组 (19只 )和对照组 (18只 )。治疗组以rh GH 0 .2 5IU/kg肌内注射 ,对照组肌内注射同等容积的0 .9%氯化钠溶液 ,3周后处死大鼠 ,开胸经升主动脉向冠状动脉内灌注 4 %多聚甲醛 2 0～ 30min固定心脏 ,心脏标本经切片处理。分别测定血浆和心肌的VEGF、bFGF的量及左室毛细血管密度。结果 :治疗组与对照组在AMI后 3周其血浆bFGF、VEGF浓度均较实验开始时明显增加 (P <0 .0 5 )。治疗组较对照组升高更加显著 ,分别为 (6 8.72± 4 .5 7)∶(35 .6 0±4 .31)和 (4 7.0 5± 5 .13)∶(32 .13± 5 .70 ) (均P <0 .0 5 )。大鼠心肌内bFGF及VEGF治疗组均较对照组高 ,分别为 (79.0 5± 6 .96 )∶(30 .7± 3.4 9)和 (72 .0 5± 6 .73)∶(39.33± 6 .78) (均P <0 .0 1)。血浆bFGF、VEGF的浓度与心肌内毛细血管密度呈正相关 (r分别为 0 .91和 0 .86 ,均P <0 .0 1)。结论 :rh GH能促进AMI大鼠心肌细胞生长因子bFGF和VEGF的表达和分泌     

阵发性房室结折返性室上性心动过速射频消融临床观察

目的: 探讨延迟缺血预处理（delayed ischemic preconditioning,DIPC）对急性心肌梗死(AMI)大鼠远期的心肌保护及其促进小动脉再生的作用。方法: 将54只SD大鼠随机分为4组,即①缺血预处理(IPC)+AMI组:于IPC后24 h,结扎冠状动脉建立AMI大鼠模型(n=24);②AMI组:开胸后,只穿线不进行IPC,于24 h后结扎冠脉建立AMI大鼠模型(n=24);③IPC组:只进行IPC不结扎冠脉(n=3);④假手术组:开胸后,既不进行IPC操作也不结扎冠状动脉(n=3)。前两组于模型建立后3 d、7 d和14 d,用免疫组化染色法检测梗死边缘区毛细血管新生及小动脉再生;后两组分别于IPC后及假手术后24 h,用免疫组化染色法检测梗死边缘区毛细血管新生及血管内皮生长因子（VEGF）、血小板源生长因子-B（PDGF-B）表达。14 d后采用小动物超声检测心功能,Masson’s Trichrome染色法测量心肌梗死(MI)面积。结果: IPC组于IPC后24 h,缺血区的心肌中可见毛细血管新生,VEGF及PDGF-B表达明显增加（与假手术组相比,P<0.05）。与AMI相比,IPC+AMI组于建模后3 d、7 d和14 d,梗死边缘区心肌中毛细血管的密度和小动脉的密度均明显增加（P<0.05）,MI面积减小（P<0.05）,心功能改善（与AMI组相比,左室短轴缩短率增高,P<0.05）。结论: DIPC可减小MI的面积,改善心功能,这一作用与其增加梗死边缘区中的小动脉再生有关;缺血区心肌中VEGF及PDGF-B表达的增加可能是小动脉再生的刺激因素。     

硝酸异山梨酯对大鼠缺血心肌血管新生的影响

目的观察硝酸异山梨酯对急性心肌梗死(AMI)大鼠缺血心肌组织形态、梗死面积及毛细血管新生的影响。方法Wistar大鼠90只建立AMI模型后,随机分为5组,分别为正常组,假手术组,模型组,硝酸异山梨酯低剂量组(IDL组)和硝酸异山梨酯高剂量组(IDH组),每组18只。大鼠饲养7、14天后各随机处死9只,截取心肌组织,进行光镜、电镜观察,利用NBT染色法测定心肌梗死面积,应用免疫组织化学法测定Ⅷ因子,进而计算缺血心肌微血管密度(MVD),通过RT-PCR技术检测血管内皮生长因子(VEGF)及碱性成纤维细胞生长因子(bFGF)基因表达情况。结果光镜下观察,缺血区可见炎细胞浸润、心肌肿胀、梗死区纤维化。与模型组比较,IDL组和IDH组7、14天心肌梗死面积明显缩小,MVD明显增加(P<0.05);正常组、假手术组VEGF mRNA、bFGF mRNA表达有所减少,而IDH组则有所增加。结论硝酸异山梨酯可明显缩小AMI大鼠梗死面积,促进缺血心肌的毛细血管新生,对心肌缺血损伤具有保护作用。     

碱性成纤维细胞生长因子在鼠缺血心肌中表达及其促血管新生作用

目的 探讨腺病毒穿梭质粒介导的碱性成纤维细胞生长因子(bFGF)基因质粒在大鼠缺血心肌中的表达情况及其对缺血心肌血管新生、梗死面积的影响.方法 42只健康SD大鼠接受冠状动脉左前降支结扎术,存活30只,随后随机分为治疗组(n=15)和对照组(n=15),治疗组于心肌梗死区和正常区交界处局部注射100 μl bFGF基因(1 μg/μl),对照组以等体积生理盐水处理.4 w后观察红色荧光蛋白(RFP)和bFGF 表达情况.微血管计数和氯化三苯四氮唑(TTC)分别检测血管新生情况和梗死面积.结果 ①基因转染后4 w的心肌冰冻切片中均可见RFP表达;治疗组心肌组织bFGF mRNA表达水平较对照组明显增高[1.238±0.323 vs 0.771±0.102(P＜0.05)],仅在治疗组检测到bFGF 蛋白表达.②治疗组微血管密度明显高于对照组[141.13±17.65 vs 75.58±6.59/视野(P＜0.05)];治疗组梗死面积小于对照组[16.32±0.43 vs 17.00±0.57%(P＜0.05)].结论 重组bFGF裸质粒经心肌内直接注射后能有效表达并发挥促进梗死后心肌血管新生和缩小梗死面积的作用.     

阿托伐他汀对糖尿病心肌梗死大鼠视网膜及心肌血管新生双向性研究

目的探讨阿托伐他汀对糖尿病心肌梗死大鼠视网膜心肌血管新生的双向性作用及机制。方法雄性SD大鼠80只,随机分为3组。正常组30只,心梗组(AMI组)25只,糖尿病心梗组(AMI+DM组)25只。通过结扎前降支建立心肌梗死模型,腹腔注射链脲佐菌素65 mg/kg建立糖尿病模型。糖尿病心肌梗死模型以结扎前降支先建立心肌梗死模型再腹腔注射脲佐菌素建立糖尿病模型,造模成功后,开始以2.5 mg/250 g剂量阿托伐他汀溶液灌胃,正常组以同等剂量生理盐水灌胃,大鼠分别于4个月时按比例随机处死。取心脏、视网膜做免疫组化观察心肌组织、视网膜血管内皮生长因子(VEGF)蛋白的表达情况。结果 AMI组心肌细胞VEGF表达高于正常组心肌细胞VEGF表达[(7158.4±525.2) vs.(3263.5±454.5)ng/L],AMI+DM组VEGF表达也高于正常组[(7058.4±435.7) vs.(3263.5±454.5)ng/L],差异均有统计学意义(P0.05);AMI+DM组视网膜VEGF表达低于正常组VEGF表达[(2671.2±424.1)vs.(3345.5±321.5)ng/L],也低于AMI组[(2671.2±424.1)vs.(3097.5±310.7)ng/L],差异均有统计学意义(P0.05)。结论他汀类药物能够在促进心肌梗死心肌VEGF蛋白表达的同时抑制糖尿病大鼠视网膜VEGF表达,在延缓视网膜病变进展的同时促进梗死心肌部位血管新生。     

单硝酸异山梨酯类制剂对急性心肌梗死血管内皮生长因子表达的作用

目的:结扎小型猪冠状动脉左前降支(left anterior descending,LAD)建立急性心肌梗死(a-cute myocardial infarction,AMI)模型,评价和探讨单硝酸异山梨酯类制剂对AMI后血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法:中华小型猪48只,全麻下开胸结扎LAD远段,建立急性心肌梗死(AMI)模型,术后随机分为实验组(24只)和对照组(24只),实验组口服长效硝酸酯类制剂(异乐定缓释胶囊,50 mg/d),对照组口服安慰剂,分别于服药后2 w、4 w、6 w和8 w取梗死区周围心肌组织标本,采用Western Blotting法及Realtime PCR法分别检测不同时间2组梗死区周围心肌组织VEGF表达水平。结果:与对照组相比,在4 w、6 w,实验组梗死区周围心肌组织VEGF表达水平均显著高于对照组[(1 819.0±408.4)vs.(1 247.5±356.8);(2 054.4±380.3)vs.(1 937.5±506.2),P<0.05]。结论:单硝酸异山梨酯类制剂能改善小型猪急性心肌梗死后,梗死区周围心肌组织VEGF表达水平,且以4 w、6 w时最为显著。     

SHH信号通路激活对急性心肌梗死大鼠缺血心肌血管再生的作用

目的 探讨SHH(sonic hedgehog)信号通路激活对急性心肌梗死(AMI)大鼠缺血心肌血管再生作用及机制。方法 雄性成年SD大鼠80只,体质量（150~200）g采用结扎大鼠左前降支的方法制备AMI大鼠模型,随机分为单纯心肌梗死(AMI)组,外源性重组人SHH蛋白（rhSHH）处理组,SHH信号通路抑制剂Cyclopamine(CYC)处理组,连续处理7 d后,利用VIII因子免疫组织化学染色测定rhSHH对AMI大鼠缺血心肌微血管密度的影响;TTC染色观察各组心肌梗死面积;ELISA和RT-PCR方法测定AMI大鼠缺血心肌促血管再生相关的指标血管内皮生长因子(VEGF),碱性成纤维细胞生长因子(bFGF)及血管生成素(Ang)-1的血清和mRNA表达;Western blot检测各组SHH信号通路相关蛋白SHH,SMO,Gli-1的蛋白表达。结果 与AMI组相比,rhSHH处理后缺血心肌微血管密度显著增加（P<0.05）,心肌梗死面积减小（P<0.01）,血管生长因子VEGF,bFGF,Ang-1的血清水平和mRNA表达显著增加（P<0.01）,心肌梗死边缘区SHH信号通路下游靶分子(SHH,SMO,Gli-1)的蛋白表达显著增加（P<0.05）;这种影响可以被SHH信号通路抑制剂Cyclopamine所逆转（P<0.01）。结论 激活SHH通路可增加缺血心肌血管生长因子VEGF,bFGF,Ang-1的表达,促进急性心肌梗死大鼠的血管再生。     

急性心肌梗死后血管内皮细胞生长因子及碱性成纤维细胞生长因子表达动态变化

目的　以急性心肌梗死大鼠为模型,观察血管内皮细胞生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)在心肌中的表达,探讨急性缺血缺氧刺激下VEGF和bFGF表达变化与新生血管形成的关系及意义。方法　建立Wistar大鼠急性心肌梗死模型,分为对照组和急性心肌梗死组( 3d ,7d ,1 4d ,2 8d ,4 2d ,56d)。免疫组化检测心肌细胞和内皮细胞中VEGF和bFGF的表达,Ⅷ因子相关抗原标记内皮细胞,检测新生毛细血管密度。结果　实验组心肌梗死后VEGF和bFGF产生量迅速增加,梗死区VEGF和bFGF的表达在梗死后第7天达高峰,2 8天开始下降,4 2天和56天时表达明显下降,新生毛细血管密度与两者产生量成正相关,与对照组比较差异有统计学意义。结论　在心肌梗死急性缺血期心肌细胞和内皮细胞能通过自身分泌VEGF和bFGF协同刺激血管内皮细胞增殖,促进血管形成,从而改善缺血心肌的血液供应。二者的表达在梗死后第7天达到最高峰,第2 8天时开始下降,为选择在表达消退期应用外源性VEGF和bFGF进行基因治疗提供了实验依据。     

激活Notch信号的骨髓间充质干细胞心肌移植促血管新生的研究

目的:探讨干预Notch信号的骨髓间充质干细胞(BMSCs)移植对心肌梗死（MI）大鼠心肌中治疗性血管新生的作用及其机制。方法: 60只 Wistar大鼠通过结扎冠状动脉前降支(LAD)建立MI模型。建模后2周,进行相应处理后,随机分为激活Noth信号的BMSCs移植实验组（D组）、BMSCs移植对照组（E组）、培养液移植对照组（C组）及MI模型对照组（B组）,每组15只大鼠。另选取10只大鼠为假手术对照组（A组）。4周后,观察细胞生长及增殖情况,运用ELISA法血浆中VEGF浓度,免疫组织化学法及Western blot法测定缺血心肌中血管内皮细胞生长因子（VEGF）蛋白的表达及缺血区心肌中毛细血管密度的改变。结果: BMSCs在梗死区中可增殖分化为内皮细胞,与B组、C组及A组相比,D组、E组缺血心肌中VEGF蛋白的表达增多及毛细血管密度均明显增加(P<0.01),D组较E组更明显(P<0.05)。结论: Notch信号可促进心肌梗死区BMSCs向内皮细胞分化, 并通过自分泌和旁分泌的方式增加缺血心肌中VEGF的表达,从而促进缺血心肌中毛细血管新生。     

重组人生长激素对心肌梗死大鼠心功能及心肌炎性因子表达的影响

目的 观察重组人生长激素(rhGH)对大鼠急性心肌梗死后心功能及心肌炎性因子表达的影响. 方法 结扎大鼠左冠状动脉前降支建立心肌梗死模型,将术后24 h存活的大鼠随机分为对照组和rhGH组,另设假手术组.rhGH组给予rhGH 2 mg.kg-1.d-1皮下注射,对照组和假手术组给予等体积的生理盐水皮下注射,4周后观察rhGH对大鼠心功能及心肌细胞肿瘤坏死因子-α(TNF-α)、白介素-1p(IL-1p)、白介素-6(IL-6)、白介素-10(IL-10)mRNA表达的影响. 结果 与假手术组比较,对照组心肌组织中促炎性细胞因子TNF-α、IL-1β、IL-β和IL-10 mRNA表达(假手术组分别为0.10±0.02、0.08±0.01、0.18±0.01和0.14±0.05;梗死区分别为0.77±0.15、0.93±0.17、1.10±0.14和0.73±0.11;非梗死区分别为0.88±0.14、0.95±0.17、1.18±0.11和0.83±0.16)明显升高.与对照组比较,rhGH组心肌组织中TNF-α、IL-1β、IL-6 mRNA表达(梗死区分别为0.35±0.10、0.36±0.10、0.43±0.11;非梗死区分别为0.51±0.10、0.42±0.11、0.51±0.12)明显下降,IL-10 mRNA表达(梗死区为1.18±0.18;非梗死区为1.21±0.22)升高,P＜0.05.心脏超声显示rhGH组左室功能明显改善. 结论 早期rhGH治疗改善了心肌梗死大鼠心肌炎性因子表达和心脏功能.rhGH有效改善心功能与其降低心肌细胞促炎细胞因子和升高抗炎因子的作用有关.     

Assessment of myocardial viability using myocardial contrast echocardiography

Myocardial contrast echocardiography (MCE) is a technique that uses microbubbles as a tracer during simultaneous ultrasound of the heart. The microbubbles can be used to provide quantitative information regarding the adequacy of myocardial blood flow (MBF), as well as the spatial extent of microvascular integrity. In acute myocardial infarction, MCE can identify the presence of collateral flow within the risk area, and can therefore predict preservation of myocardial viability and ultimate infarct size even prior to reperfusion. After reperfusion, the extent of microvascular no-reflow can be determined, and has significant implications for recovery of left ventricular function. In chronic ischemic heart disease, MCE has also been shown to successfully differentiate viable from necrotic myocardium. This technique can accurately predict recovery of function after revascularization. More importantly, MCE can be used to identify viable segments that may help to prevent infarct expansion and remodeling, and thus improve patient outcomes.     

Assessment of myocardial viability with myocardial contrast echocardiography

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.     

Anaerobic myocardial abscess following myocardial infarction

An anaerobic myocardial abscess due to Bacteroides fragilis developed in a 60-year-old man when he had an acute myocardial infarction while recuperating from surgery for a paracolonic abscess. Anaerobic bacteremia is a common event and may lead to infection in areas of low oxygen tension far removed from the original portal of entry.     

经静脉心肌声学造影评价心肌梗死后存活心肌的价值

目的　探讨经静脉心肌声学造影 (MCE)对心肌梗死后存活心肌的诊断价值。方法　 2 4例心肌梗死患者用二维超声评价室壁运动情况 ,同时经静脉进行MCE ,以 3个月后静态超声心动图左室心肌节段性运动改善为依据评价MCE对心肌梗死后存活心肌的诊断价值。结果　在 2 4例病人的 384个心肌节段中 ,运动异常节段 184个。在运动异常的 184个节段中 ,MCE1分 39段 ,0 5分 5 0段 ,0分 95段。 3个月复查 79个节段有运动改善 ,其中 39段来自MCE1分的心肌 ,4 0段来自MCE0 5分的心肌。MCE对预测心肌梗死后室壁运动改善的敏感性、特异性、阳性预测值、阴性预测值及准确率分别为 :10 0 %、89 7%、84 8%、10 0 %和 94 6 %。结论　MCE能比较准确地预测心肌梗死后心肌的存活性     

Differentiation of aborted myocardial infarction from masquerading myocardial infarction

We read with great interest the article by Verheugt et al.¹dealing with aborted myocardial infarction (MI) as a new targetfor reperfusion     

Assessment of fetal myocardial performance using myocardial deformation analysis

Conventional techniques for the assessment of cardiac function on the basis of M-mode or 2-dimensional modalities are technically difficult, load dependent, and provide information on global ventricular function only. Newer techniques, which analyze myocardial performance, such as tissue velocity, strain, and especially the less load dependent strain rate, may provide more appropriate information. Myocardial systolic and diastolic motion and performance were calculated using tissue velocity, strain, and strain rate imaging on a large cohort of normal fetuses. The assessment of myocardial performance was feasible in all 98 normal fetuses. Normal systolic and diastolic values for tissue velocity, strain, and strain rate were established. All data were highly reproducible. Tissue velocity was age dependent, whereas strain and strain rate were stable throughout gestation. All parameters were heart rate independent. In conclusion, fetal myocardial velocity, strain, and strain rate measurements are easy to obtain and reproducible, and therefore, may serve as reference data. Increases in tissue velocity throughout gestation probably reflect the growth of the fetal heart, whereas intrinsic myocardial properties as measured by strain rate do not change. In comparison with recently published myocardial performance values in children, these strain rate data suggest that fetal myocontractile properties that are already established during the second half of pregnancy remain constant throughout gestation and after birth.     

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and ¹²⁹Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of ¹²⁹Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia.Six dogs were given ¹²⁹Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given ¹²⁹Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of ¹²⁹Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.     

心肌缺血预适应对急性心肌梗死影响的观察

目的:探讨心肌缺血预适应对急性心肌梗死(AMI)临床表现及其预后的影响。方法:根据AMI前有无心绞痛发作分为预缺血组和无预缺血组,分组观察AMI患者血清肌酸磷酸激酶(CPK)峰值,住院期间并发症(心衰、心源性休克、严重心律失常),以及住院期间心性病死率。结果:预缺血组血清CPK峰值明显低于无预缺血组(P<0.05),住院期间心源性休克及严重心律失常发生率明显低于无预缺血组(P<0.05)。结论:心肌缺血预适应可减轻心肌坏死程度,缩小梗死面积,并减少AMI并发症的产生。