超声评价急性心梗早期左室重构与内皮功能障碍的关系

目的 探讨急性心肌梗死(AMI)早期左室重构(LVR)与内皮功能障碍(ED)的关系.方法 对30例病程6周的AMI患者应用超声分别测量左心室舒张末期内径(LVDd)、左室梗死区室壁厚度(Td)、左室舒张末容积(LVEDVI)、左室收缩末容积(LVESVI)和左室射血分数(LVEF)、静息状态及反应性充血后肱动脉内径,计算反应性充血诱发的肱动脉内径扩张百分率.对各项心内结构指标与内皮依赖性舒张功能(EDD)指标做相关性分析.结果 Td与EDD呈正相关(r=0.591,P＜0.01)、LVESVI与EDD呈负相关(r=-0.414,P＜0.05)、LVEF与EDD呈正相关(r=0.493,P＜0.01).结论 AMI后早期LVR与ED有关,ED参与了AMI早期LVR的发生发展.     

兔心肌梗死后2个月肥大心室肌细胞的电生理研究

背景心肌梗死后电重构与梗死后时间和区域相关.目的研究陈旧性心肌梗死非梗死区肥大心室肌细胞离子通道电流的变化,探讨心肌梗死后肥大心肌发生心律失常的可能的离子机制.设计随机对照实验研究.地点、材料和干预所有实验过程在石家庄市白求恩国际和平医院心内科中心实验室完成.新西兰纯种大耳白兔20只,按随机抽签法分为两组心肌梗死动物模型组和正常对照组.采用结扎兔冠状动脉左前降支的方法建立急性心肌梗死动物模型,应用膜片钳全细胞记录方法.主要观察指标梗死后2个月心外膜远离梗死区组与梗死区组及正常对照组心室肌细胞L-钙通道电流(L-calcium current,ICa-L)、瞬间外向钾电流(transient outward current,Ito)的变化.结果①远离梗死区组细胞电容[(155.7±5.8)pF,n=41]明显大于对照组[(120.3±6.2)pF,n=35]和梗死区组[(130.4±7.8)pF,n=38](t=2.642,2.613,P均＜0.01).②ICa-L远离梗死区组ICa-L电流峰值(0 mV)为[(826.12±121.31)pA,n=21],较对照组[(670.21±183.32)pA,n=10]和梗死区组[(629.43±172.12)pA,n=11]明显增大(t=2.451,2.732,P均＜0.05).但远离梗死区组电流密度峰值为(5.32±0.78)pA/pF,较对照组[(5.58±1.53)pA/pF]略下降,与梗死区组[(4.84±1.48)pA/pF]和对照组比较无显著性意义(P均＞0.05).③Ito远离梗死区组[(13.21±4.13)pA/pF,n=23]和梗死区组[(10.61±4.12)pA/pF,n=18]的Ito电流密度(+60mV时)均明显低于对照组[(17.39±5.24)pA/pF,n=16](t=3.591,2.725,P均＜0.01).但远离梗死区组明显高于梗死区组(t=2.429,P＜0.05).结论心肌梗死后2个月,远离梗死区心室肌细胞电容明显增大,反映心肌细胞发生代偿性肥大.远离梗死区心室肌细胞ICa-L幅值升高,但Ito电流密度明显下降,ICa-L电流密度轻度下降,可导致动作电位平台期延长,复极异常,异常自律性的增加,并且心室不同部位存在电生理异质性,可能是导致陈旧性心肌梗死出现室性心律失常的离子基础.     

冠脉侧支循环与心肌细胞凋亡关系的实验研究

目的：探讨心肌梗死后侧支循环形成与心肌细胞凋亡的关系。方法：建立大鼠急性心肌梗死模型。采用放射性微球法测量局部心肌血流量，HE染色计数血管数，TUNEL法检测细胞凋亡。观察结扎后3d、7d、14d和28d侧支循环与心肌细胞凋亡的一系列演变过程，采用相关分析两者的关系。结果：梗死周边区凋亡心肌细胞数随时间逐渐降低。梗死区和周边区的局部心肌血流量在结扎后3d最低，以后逐渐增加，与血管计数的增加相平行。梗死周边区的侧支血流量和血管计数与该区域的凋亡心肌细胞数呈负相关（r分别为-0．961和-0．805，P〈0．01）。结论：梗死周边区侧支血管的生长可减少该区域心肌细胞凋亡的发生。     

不同种类自体骨髓干细胞移植对梗死心肌左室重构的效果比较

背景:骨髓干细胞移植可改善心功能、预防心室重构,目前用于移植的成体骨髓干细胞有骨髓单个核细胞、骨髓间充质干细胞和内皮祖细胞等,不同种类的骨髓干细胞移植后的效果及具体机制尚不清楚。目的:比较自体骨髓单个核细胞、骨髓间充质干细胞冠状动脉移植对急性心肌梗死后心室重构的影响。设计、时间及地点:随机对照动物实验,于2005-03/2006-12在河北省人民医院临床研究中心、河北医科大学电镜室及大连宝生物进行。(basic fibroblast growth factor,bFGF)材料:36只冀中白猪随机分为4组:假手术组6只、模型组10只、骨髓单个核细胞组10只、骨髓间充质干细胞组10只。方法:采用梯度密度离心法分离培养猪自体骨髓单个核细胞,以贴壁法分离培养猪自体骨髓间充质干细胞,移植前均行胶体金标记。除假手术组外,其余3组均以球囊导管压迫冠状动脉前降支的方法建立猪急性心肌梗死模型。造模后90min,经导管由冠状动脉腔内骨髓单个核细胞组移植自体骨髓单个核细胞(6.0±1.3)×107个,骨髓间充质干细胞组移植自体骨髓间充质干细胞(4.5±2.1)×107个,培养28d。主要观察指标:光镜及电镜观察心肌组织病理学改变;超声检查心功能变化;免疫组织化学检测心肌血管数、心肌细胞凋亡、心肌组织核因子κB及肌钙蛋白I阳性表达情况,及其与心功能的关系;RT-PCR法检测心肌血管内皮生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)mRNA的表达,及其与心功能的关系。结果:①骨髓间充质干细胞组在梗死区、梗死边缘区均可见大量血管增生,冠脉血管周围可见异常细胞团生长,骨髓单个核细胞组有较多的毛细血管"芽生"现象。②细胞移植前各组心功能指标基本相似(F=1.550,P>0.05)。移植后28d与模型组比较,其余3组左心室射血分数均明显降低(F=5.30,P<0.05)。③与模型组比较,骨髓单个核细胞组梗死区及梗死边缘区的血管数明显增加(F=29.56～34.87,P<0.01),骨髓间充质干细胞组无变化;移植细胞两组的梗死区、梗死边缘区心肌细胞凋亡率均显著降低(F=14.31～35.34,P<0.01),肌钙蛋白I阳性率均明显升高(F=19.05,P<0.01);梗死边缘区核因子кB阳性率均明显降低(F=19.05,P<0.01)。④骨髓单个核细胞组梗死边缘区VEGF基因的表达显著高于模型组、骨髓间充质干细胞组(F=49.41,P<0.01)。骨髓间充质干细胞组梗死边缘区bFGF基因的表达显著高于模型组、骨髓单个核细胞组(F=4.71,P<0.01)。⑤左室射血分数与心肌细胞凋亡率、心肌核因子κB呈负相关(r=-0.4411,P<0.05;r=-0.5796,P<0.01);与血管数、VEGF及bFGF表达呈正相关(r=0.775,P<0.01;r=0.5651,P<0.05;r=0.5735,P<0.05)。结论:经冠脉自体骨髓单个核细胞或骨髓间充质干细胞移植均可减轻心肌梗死后左心室重构,心功能的改善与干细胞移植后增加心肌血管数量及心肌VEGF,bFGF表达、减少心肌细胞凋亡及核因子κB水平有关。骨髓单个核细胞移植促心肌血管增生及VEGF的表达均优于骨髓间充质干细胞,而后者促bFGF基因表达的作用优于前者。     

当归对心肌梗死后心肌细胞凋亡和心室重构的影响

目的 探讨当归对大鼠心肌梗死后左室功能、梗死灶边缘区心肌细胞凋亡及凋亡相关基因变化的干预作用及其可能机制.方法 将120只雄性Wistar大鼠随机分为假手术组(sham组)、急性心肌梗死(AMI)组和当归干预组.采用结扎大鼠冠状动脉左前降支制备AMI模型.当归干预组于术后24 h开始腹腔注射当归注射液(20 ml·kg-1·d-1,相当于含生药量10 g·kg-1·d-1);AMI组和sham组注射等量生理盐水.术后1、2、3和4周记录血流动力学改变后处死动物,分别采用原位末端缺刻标记法(TUNEL)和免疫组化法检测心肌细胞凋亡系数,以及促凋亡基因Bax和抗凋亡基因Bcl-2的蛋白表达水平.结果 ①AMI发生后左室功能明显降低,当归干预4周后可改善左室功能(P＜0.05或P＜0.01).②AMI组和当归干预组比较心肌梗死面积差异无统计学意义;AMI组4周后全心和左室相对重量均较sham组显著增加(P均＜0.01),当归干预4周后可明显减轻全心和左室相对重量(P均＜0.05).③sham组未见心肌细胞凋亡,AMI组和当归干预组梗死灶边缘区均有心肌细胞凋亡,但当归干预组心肌细胞凋亡较AMI组明显减少(P＜0.01).④与sham组比较,AMI组和当归干预组Bax和Bcl-2的蛋白表达均明显升高;而当归干预组Bcl-2的蛋白表达进一步增加,并能明显抑制Bax的蛋白表达(P＜0.05或P＜0.01).结论 心肌梗死后发生左室功能降低,梗死灶边缘区有大量的心肌细胞凋亡;当归可能通过上调Bcl-2和下调Bax的表达,使Bax/Bcl-2比值下降,从而抑制该区的心肌细胞凋亡,减少心肌细胞丢失,进而改善左室功能,减轻心室重构.     

胚胎干细胞梗死区中心和周边移植治疗急性心肌梗死

背景:现有治疗手段不足以补充梗死心肌,研究表明干细胞移植有可能促使心肌和血管再生,改善心功能和预后.目的:观察急性心肌梗死区中心和周边移植胚胎干细胞后心肌组织形态学及血液动力学的变化.设计、时间及地点:随机对照动物观察,于2007-03/2008-10在中南大学湘雅医学院人体解剖学与神经生物学系神经生物学实验室完成.材料:SPF级Wistar大鼠40只,随机分为4组:正常对照组、梗死模型组、中心移植组、周边移植组,10只/组.胚胎干细胞-D3株(embryonic stem cells-D3,ES-D3)、布法罗大鼠肝细胞均由中国科学院上海细胞所提供.方法:ES-D3细胞复苏后,以(2.0～5.0)× 107L-1种植于培养瓶中,加入含布法罗大鼠肝细胞的条件培养基体外培养分化.除正常对照组外,余3组结扎冠状动脉左前降支建立急性心肌梗死模型.造模后1周接受细胞移植,ES-D3细胞于移植前1 d进行BrdU标记,以胚胎干细胞培养基调整密度至1×109L-1.中心移植组在梗死区选3个点,每点注入10 μL细胞悬液(含104个细胞)至心室壁内;周边移植组在梗死区周边选3个点同法注入等量细胞悬液.主要观察指标:免疫组化及血流动力学指标检测结果.结果:布法罗大鼠肝细胞条件培养基体外培养的ES-D3细胞,呈相对规则的巢状集落样生长,分化8d即可见部分拟胚体出现自发的节律性收缩活动,心肌肌钙蛋白T免疫染色呈阳性,电镜下可见肌管、肌纤维等肌性结构,证实已分化为心肌细胞.周边移植组BrdU免疫荧光染色呈阳性,而中心移植组呈阴性,进一步对BrdU免疫荧光染色阳性细胞行双抗染色,可见心肌肌钙蛋白T呈阳性表达.移植后4周与正常对照组比较,梗死模型组左室收缩、dp/dtmax均减小(P＜0.01),左室舒张末期压上升(P＜0.01),左室质量、左室质量指数均升高(P＜0.01).与梗死模型组比较,中心移植组各项血流动力学指标无明显变化(P＞0.05);周边移植组左室收缩压、±dp/dtmax均显著升高(P＜0.01),左室舒张末期压显著减小(P＜0.01),左室质量、左室质量指数,梗死面积均显著减小(P＜0.01).结论:急性心肌梗死后于梗死周边区移植胚胎干细胞可以阻止心室重构、减少瘢痕面积、改善心功能.     

心肌梗死后心肌细胞凋亡及左室重塑过程中肝细胞生长因子的作用

目的:探讨外源性肝细胞生长因子(hepatocytegrowthfactor,HGF)对心肌梗死后心肌细胞凋亡及左室重塑的影响。方法:将56只新西兰兔随机分为4组:假手术组、假手术+HGF组、对照组和干预组。结扎左冠状动脉前降支复制急性心肌梗死模型。干预组静脉注射给予HGF2mg/(kg·12h),4周后测心功能、左室重塑指标,取出心脏,梗死区/缺血区重量比为梗死范围。TUNEL法染色检测细胞凋亡。Westernblot法测定凋亡蛋白Bcl-2的表达。结果:与假手术组相比,对照组的左室舒张末容积、左室相对重量、左室壁厚度均显著升高(t=3.598,2.348,2.324,P<0.05～0.01),左室缩短分数(leftventricularfractionofshortening,LVFS)、左室射血分数(leftventricularejectionfraction,LVEF)均显著降低(t=4.311,3.330,P<0.01)。HGF干预组LVESV,LVEDV显著低于对照组(t=2.810,2.449,P<0.01);LVFS及LVEF均显著升高。HGF干预组细胞凋亡率、心肌梗死范围均低于对照组(t=2.302,2.344,P<0.01)。左室腔直径与心肌细胞凋亡率呈正相关(r=0.801,P<0.01)。干预组梗死心肌周围bcl-2表达(灰度值1.37)显著高于对照组(灰度值0.17)(t=21.043,P<0.01)。结论:HGF能减少心肌梗死范围、降低心肌细胞凋亡率并能限制心肌梗死后的左室重塑,改善心功能,其作用机制可能与其抗凋     

自动功能成像评估急性心肌梗死患者左心室功能及梗死范围

目的 应用二维斑点追踪自动功能成像(AFI)技术评价急性心肌梗死(AMI)患者的左心室功能,及其与AMI常规心肌标志物肌钙蛋白T(cTnT)以及心电图ST段抬高的相关性,探讨AFI的临床应用价值。方法 获取46例首发AMI患者（心肌梗死组）和30例年龄性别相关受检者（对照组）的二维超声图像,同时记录12导联心电图和AMI患者入院24 h的cTnT值,应用AFI技术实时获取左室收缩峰值纵向应变(LPSS)及其牛眼图。结果 与对照组相比,心肌梗死组的左室射血分数(LVEF)、LPSS明显减低(P ＜0.001),ST段明显抬高(P＜0.001);整体LPSS与梗死节段LPSS均与LVEF呈负相关,整体LPSS与LVEF的相关性较高（r=-0.660）;整体LPSS与梗死节段LPSS均与cTnT呈正相关(P＜0.001),LVEF与cTnT呈负相关(P=0.002),梗死节段LPSS与cTnT的相关性较高(r=0.598);整体LPSS与梗死节段LPSS均与ST段抬高呈正相关(P＜0.05)。结论整体LPSS能准确评价AMI患者的左室收缩功能,梗死节段LPSS能准确评价AMI患者的梗死受累范围和程度。AFI作为简易快捷的程序性诊断工具可为临床评价AMI提供有价值的信息。     

经冠状动脉移植自体骨髓单个核细胞和间充质干细胞对急性心肌梗死模型心功能的改善

目的:为保护濒死心肌提供机会窗口,对比观察经冠脉移植自体骨髓单个核细胞或间充质干细胞后,实验性急性心肌梗死动物心功能变化及心肌组织核转录因子кB、心肌细胞凋亡情况。方法:实验于2005-03/2006-11在河北省人民医院实验中心完成。选用24只雄性冀中白猪,随机数字表法分为4组:正常对照组、模型组、单个核细胞组、间充质干细胞组,6只/组。①24只猪均以盐酸氯胺酮200mg臀部肌肉注射麻醉后,分别于各自右侧股骨抽取骨髓20mL,采用Fercoll法分离获得骨髓单个核细胞,加入胶体金溶液,培养12～16h待用。分离过程中取出含有骨髓单个核细胞成分的细胞层,常规培养传代,每3d换液1次,贴壁生长细胞即为骨髓间充质干细胞,加入胶体金溶液,培养24h待用。②除正常对照组外,其余各组均经导管球囊封闭第一对角支以远的前降支,复制猪急性心肌梗死模型。单个核细胞组、间充质干细胞组均于造模后立即开通前降支,分别经球囊注入预先分离的骨髓单个核细胞6×108个、间充质干细胞6×108个。模型组造模后于梗死1h开通前降支,经球囊注入磷酸盐缓冲液10mL。③各组分别于术前及术后4周经心脏超声检测心功能,取材行病理学检查、心肌组织核转录因子кB的免疫组织化学检测及心肌细胞凋亡检测。结果:24只雄性白猪均进入结果分析。①心功能变化:术前各组左心室收缩末内径、左心室舒张末内径、左心室射血分数、短轴缩短率基本相似。移植术后4周,正常对照组、单个核细胞组、间充质干细胞组左心室舒张末内径均明显低于模型组(F=4.68,P=0.01),左心室射血分数及短轴缩短率均明显高于模型组(F=5.14,P=0.01;F=3.32,P=0.04),各组左心室收缩末内径差异无显著性意义(F=1.64,P=0.21)。②心肌组织病理学改变:电镜下单个核细胞组、间充质干细胞组在梗死边缘区可见有胶体金颗粒的不成熟的心肌细胞,胞质中散在肌丝结构,肌丝排列紊乱不规则。③心肌组织核转录因子кB阳性率表达:与模型组比较,单个核细胞组、间充质干细胞组的梗死边缘区核转录因子кB阳性率明显降低(F=25.59,P=0.0001);正常心肌区核转录因子кB阳性率亦明显降低(F=18.20,P=0.0001)。④心肌细胞凋亡检测结果:与模型组比较,单个核细胞组、间充质干细胞组在心肌梗死区细胞凋亡率均明显降低(F=6.63,P=0.0027),梗死边缘区细胞凋亡率亦明显降低(F=36.07,P=0.0001)。正常心肌区单个核细胞组细胞凋亡率与模型组基本相似(F=9.69,P=0.004),但间充质干细胞组有所降低。⑤心功能与心肌细胞凋亡及心肌组织NF-кB的相关性:急性心肌梗死4周时,左心室射血分数与心肌细胞凋亡、心肌组织核转录因子кB均呈负相关(r=0.613,P=0.001;r=-0.437,P=0.033)。心肌细胞凋亡与心肌组织核转录因子кB呈正相关(r=0.672,P=0.002)。结论:经冠脉移植骨髓单个核细胞和间充质干细胞均可改善实验性急性心肌梗死动物的心功能,与梗死边缘区核转录因子кB表达降低及心肌细胞凋亡减少有关。骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植。     

醛固酮受体拮抗剂对急性心肌梗死大鼠心肌细胞凋亡的影响

目的 研究螺内酯对急性心肌梗死心肌细胞凋亡的影响.方法 通过结扎左冠状动脉前降支造成大鼠左心室大面积心肌梗死模型.大鼠随机分为心肌梗死组24只和螺内酯组24只,另设假手术组24只,每时点6只,分别于术后2天、7天、14天、21天观察下列指标:①用免疫组织化学方法测定非梗死区心肌组织Ⅰ/Ⅲ胶原比值;②用流式细胞学方法测定非梗死区心肌细胞凋亡率.结果 在2、7、14、21天假手术组的心肌细胞凋亡率分别为(4.05±1.21)％、(4.03±1.20)％、(4.02±1.18)％和(4.01±1.13)％,心肌梗死组分别为(22.01±1.85)％、(20.15±1.02)％、(14.27±1.14)％和(12.46±1.18)％,明显高于假手术组,而螺内酯组低于心肌梗死组(22.11±1.68)％、(18.95±1.35)％、(12.67±1.12)％、(9.67±1.08)％.与假手术组相比较,心肌梗死组非梗死区心肌组织Ⅰ/Ⅲ型胶原比值在2天时差异无统计学意义(P＞0.05),7天、14天和21天时均显著增高(P＜0.05或＜0.01),与心肌梗死组比较,螺内酯组大鼠心肌组织Ⅰ/Ⅲ型腔原比在2天、7天及14天时差异无统计学意义(P＞0.05),21天时明显降低(P＜0.05).结论 醛固酮受体拮抗剂可减少急性心肌梗死后非梗死区心肌细胞的凋亡.同时对Ⅰ/Ⅲ型胶原比值有明显的抑制作用,醛固酮受体拮抗剂可能通过减少心肌细胞凋亡而减少腔原的沉积,抑制心室重构.     

组织速度成像定量评价大鼠急性心肌梗死后左室重构的左室收缩功能

目的应用定量组织速度成像结合二维超声心动图对大鼠急性心肌梗死(Acute Myocardial Infarction,AMI) 后左室重构的左室收缩功能进行评价,以探讨定量组织速度成像评价大鼠AMI后左室重构的应用价值.方法 AMI组雌性SD大鼠(n＝12)为样本,正常组大鼠(n＝10)作对照,4周后2组均行超声心动图检查.结果与正常组相比,AMI组的左室舒张末期内径、舒张末期容积显著增加(P＜0.01);左室射血分数、左室后壁增厚率、球形指数、梗死区变薄指数等显著降低(P＜0.01);心脏长轴方向上AMI组二尖瓣环、左室侧壁各节段,短轴方向上前间隔及后壁的基底部、中部定量组织速度成像收缩期峰值速度明显下降(P＜0.05);二尖瓣环收缩期平均峰值速度与左室射血分数、球形指数等呈线性相关(r值分别为0.84 、0.70,P＜0.001).结论定量组织速度成像结合二维超声心动图能较全面、定量和无创性地评价大鼠AMI后左室重构的左室收缩功能.     

Effects of trimetazidine,a partial inhibitor of fatty acid oxidation,on ventricular function and survival after myocardial infarction and reperfusion in the rat

Trimetazidine (TMZ), a partial inhibitor of fatty acid oxidation, has been effective in treating chronic angina, but its effects on the development of post‐myocardial infarction (MI) left ventricular remodeling are not defined. In this study, we tested whether chronic pre‐MI administration of TMZ would be beneficial during and after acute MI. Two‐hundred male Wistar rats were studied in four groups: sham + TMZ diet (n = 20), sham + control diet (n = 20), MI + TMZ diet (n = 80), and MI + control diet (n = 80) splitted into one short‐term and one long‐term experiments. Sham surgery consisted of a thoracotomy without coronary ligation. MI was induced by coronary occlusion followed by reperfusion. Left ventricle (LV) function and remodeling were assessed by serial echocardiography throughout a 24‐week post‐MI period. LV remodeling was also assessed by quantitative histological analysis of post‐MI scar formation at 24 weeks post‐MI. During the short‐term experiment, 10/80 rats died after MI, with no difference between groups (MI + control = 7/40, MI + TMZ = 3/40, P = 0.3). In the long‐term experiment, the deaths occurred irregularly over the 24 weeks with no difference between groups (MI + control = 16% mortality, MI + TMZ = 17%, P = 0.8). There was no difference between groups as regard to LV ejection fraction (MI + control = 36 ± 13%, MI + TMZ = 35 ± 13%, P = 0.6). In this experimental model, TMZ had no effects on the post‐MI occurrence of LV dysfunction or remodeling. Further investigations are warranted to assess whether the partial inhibition of fatty acid oxidation may limit the ability of the heart to respond to acute severe stress.     

Dobutamine stress echocardiography predicts left ventricular remodeling after acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Left ventricular (LV) remodeling after acute myocardial infarction (MI) is strongly related to infarct size. The contribution of viability in the infarct zone and the presence of multivessel disease remains unknown. Because dobutamine stress echocardiography (DSE) can estimate infarct size and detect myocardial viability and multivessel disease, we postulated that DSE can accurately predict LV remodeling after acute MI. METHODS: To test this hypothesis, 30 patients age 59 +/- 15 years, 21 men, 14 with anterior MI, underwent multistage DSE (low dose, 5 to 10 microg, and peak dose) during the first week after MI occurred. Follow-up echocardiography was performed at >/=1 year. LV remodeling (2 SD increase in LV volume) occurred in 17 of 30 patients. Remodeling occurred in 12 (92%) of 13 patients with large nonviable infarct and in 1 (13%) of 8 patients with large viable infarct (P <.001). Univariate predictors of LV remodeling were baseline ejection infarct (P <.01), infarct size (number of akinetic segments at low dose P <.01), age (P <.05), and multivessel coronary disease (P <. 01). The only multivariate predictor of remodeling was infarct size. Viability of infarct zone was a negative predictor of LV remodeling. CONCLUSION: DSE performed during the first week after acute MI predicts subsequent LV remodeling. Infarct size, nonviability of the infarct zone, and age are independent predictors of LV remodeling. Myocardial viability is a strong negative predictor of LV remodeling.     

同种异体脂肪组织来源干细胞联合地黄低聚糖对心肌梗死小型猪心肌凋亡的影响

目的探讨同种异体脂肪组织来源干细胞(ASCs)联合地黄低聚糖(RGOs)对心肌梗死(MI)小型猪心肌凋亡的影响。方法球囊封堵冠状动脉前降支制备小型猪MI模型,17头小型猪造模成功,采用随机数字表法分为4组:ASCs组(n=4),RGOs组(n=4),RGOs+ASCs组(n=4)及对照组(n=5)。造模前3天、造模后1月RGOs组及RGOs+ASCs组均饲以RGOs粗提物;造模7~10 d经冠状动脉移植ASCs,RGOs组及对照组均注入0.9%氯化钠注射溶液。移植后8周检测心肌梗死边缘区细胞凋亡(TUNEL法)及Bax、Bcl-2的表达。结果与对照组比较,RGOs组及RGOs+ASCs组心肌细胞凋亡均显著降低(P<0.05,P<0.01),三组Bax的表达均明显降低(P<0.05),RGOs组及RGOs+ASCs组Bcl-2的表达均明显升高(P<0.01)。结论 ASCs联合RGOs抑制了梗死边缘区心肌细胞凋亡。     

超声评价非诺贝特对自发性高血压大鼠心肌重构的干预作用

目的 应用超声技术评价非诺贝特对自发性高血压大鼠心肌重构的影响。方法 自发性高血压大鼠（spontaneous hypertensive rats，SHR）22只随机分为SHR用药组（12只）和SHR未用药组（10只），同周龄Wistar—kyoto（WKY）大鼠10只作为正常对照。非诺贝特治疗8周，分别于实验前后进行超声心动图检查，8周末处死动物进行组织学检查。结果实验后，与WKY组相比，SHR未用药组室壁厚度、左室相对质量显著增加（P＜0．01），二尖瓣口血流流速曲线E／A值明显减小（P＜0．01），E峰减速时间明显延长（P＜0．05）；SHR用药组与SHR未用药组相比以上指标均有明显改善（P＜0．05）。SHR未用药组室间隔、左室后壁的平均声学强度（AID、心包校正的声学强度明显增高（P＜0．01），峰一峰强度明显降低（P＜0．01）；SHR用药组与SHR未用药组相比以上声学密度指标均有明显改善（P＜0．05）。超声所计算的左室相对质量与实体标本测值具有较高的相关性（r=0．729，P＜0．001）。结论 非诺贝特具有干预SHR心肌重构的作用，声学密度技术结合常规超声心动图能较全面、准确评价此作用。     

L-NAME enhances microcirculatory congestion and cardiomyocyte apoptosis during myocardial ischemia-reperfusion in rats

Besides necrosis, apoptosis is the other major mode of cardiomyocyte loss in ischemic cardiovascular disease. In the present study, we examined the hypothesis that nitric oxide (NO) protects myocardial function by improving myocardial microcirculation and attenuating cardiomyocyte apoptosis in a rat model of myocardial ischemia/reperfusion (MI/R). The left main coronary artery of anesthetized male rats was ligated for 40 min, followed by 4 h reperfusion. Four groups of animals were studied: sham operated control + saline; sham operated control + N(W)-nitro-L-arginine methyl ester (L-NAME); MI/R + saline; MI/R + L-NAME (10 mg/kg, iv, 10 min prior to reperfusion). Results show that MI/R caused a decrease in mean arterial blood pressure (MABP), cardiac index (CI), and stroke volume index (SVI). Inhibition of NO synthesis by L-NAME attenuated plasma NO levels, but increased MABP and SVR in sham control rats and rats subjected to MI/R, and further depressed left ventricular function in rats subjected to MI/R as indicated by decreased CI and SVI. Furthermore, administration of L-NAME to rats subjected to MI/R enhanced cardiomyocyte apoptosis as indicated by a significant increase in DNA fragmentation compared to rats with MI/R alone. Histological study revealed that L-NAME caused arterial constriction and congestion of red blood cells in arteries and capillaries in the peri-ischemic areas of the hearts in rats subjected to MI/R and, interestingly, also in the sham control rats. Data suggest that the mechanism of increased reperfusion injury may be attributable to a "no-reflow" phenomenon induced by L-NAME, resulting in increased cardiomyocyte apoptosis secondary to ischemia and enhanced cytochrome-c release from mitochondria. In addition, cardiac injury may be increased due to the augmented oxygen consumption of cardiomyocytes caused by the increased SVR and afterload. These results suggest that endogenous NO may act to improve myocardial microvascular perfusion, reduce SVR, and limit cardiomyocyte apoptosis, thereby, attenuating myocardial dysfunction induced by MI/R.     

Role of apoptosis in remodeling after myocardial infarction

The magnitude of an acute myocardial infarction (MI; i.e., number of dead cardiomyocytes) is the most critical determinant of subsequent left ventricular remodeling and heart failure. Also affecting the post-infarction disease process, however, are events occurring during the subacute and chronic stages of the infarction, including late cardiomyocyte death, cardiomyocyte hypertrophy, fibrosis, and expression of various cytokines. Additionally, it has been suggested that apoptosis may be responsible for a significant amount of cardiomyocyte death during the acute ischemic stage, as well as for a progressive loss of surviving cells during the subacute and chronic stages. However, there is very little direct morphological evidence of apoptosis occurring at any stage of MI, despite the availability of much indirect evidence that includes detection of DNA fragmentation and apoptosis-related factors. For that reason, the potential efficacy of therapeutic intervention to prevent apoptosis remains controversial. This review will survey available data from both animals and humans to critically assess the role of cardiomyocyte apoptosis during MI and its relevance to myocardial remodeling and heart failure. Also considered will be nonmyocyte interstitial cells, which have received less attention than myocytes despite definitive evidence of their apoptosis in the infarcted heart and recent studies suggesting that blockade of apoptosis among these cells mitigates post-infarction cardiac remodeling and heart failure. We conclude from our survey that there are many hurdles to surmount before regulation of apoptosis can be clinically applied in the treatment of MI and other heart diseases.     

超声心动图评价心肌细胞移植对Wistar大鼠心肌梗死后左心室重构及心功能的影响

目的探讨心肌细胞移植对Wistar大鼠心肌梗死后左室重构及心功能的影响。方法50只雄性Wistar大鼠结扎冠状动脉左前降支成功建立慢性心肌梗死模型，随机分为试验组，即新生鼠心肌细胞移植组25只；对照组，即细胞培养液基质移植组25只。另设假手术组15只为正常对照。心肌梗死后4周和细胞移植后4周，采用高频超声心动图评价大鼠左室形态和功能。用免疫组化技术检测试验组移植细胞的存在。结果细胞移植后4周，与对照组相比，试验组左室收缩末期内径、舒张末期内径、收缩末期容积和舒张末期容积均显著缩小（P〈0．01），左室前壁舒张末期厚度明显增厚（P〈0．01），左室射血分数和缩短率显著升高（P〈0．01）。免疫组化显示试验组心肌瘢痕区边缘有BrdU阳性细胞存在。结论心肌细胞移植可逆转心肌梗死大鼠左室重构，改善左室功能。高频超声心动图为心肌细胞移植效果评价提供了有效实用的方法。     

Contrast enhanced echocardiographic follow-up of cardiac remodeling and function after myocardial infarction in rats

Echocardiography is a reliable and commonly used method to examine cardiac diseases. Recent employment of modern technologies provides new opportunities to study left ventricular (LV) remodeling after myocardial infarction (MI) also in small rodents. LV volumes as most important prognostic parameters can be estimated by noncontrast enhanced echocardiography in rats from M-mode or single cross sections only. In this study, contrast enhanced echocardiography and volume measurements by the biplane method of discs (Simpson's rule) were applied in rats to monitor remodeling and function after MI. MI was induced in female Sprague-Dawley rats (n = 26 for MI, and n = 16 for sham). LV remodeling and heart function were serially studied by contrast enhanced echocardiography for 12 to 16 wk. At the end of the observation periods hemodynamic data were additionally measured by left and right heart catheterization. LV end systolic volume (LVESV) measured by biplane method of discs correlated best with LV developed pressure as indicator for severely impaired heart function. Interestingly, LV end systolic area (LVESA) from native short axis view correlated well with LVESV (R(2) = 0.93) and was the second best predictor for depressed heart function. Moreover, left atrial size was a powerful indicator of severely impaired heart function whereas ejection fraction or fractional area change were primarily related to infarct size. In conclusion, contrast enhanced echocardiography in rats is feasible and an economical method to study time-dependent LV remodeling and deterioration of contractile function after MI.