自体心耳肌细胞移植对心功能的影响

目的将急性分离的兔自体左心耳心肌细胞移植到自体梗死区心肌,以研究其对心功能的改善情况。方法结扎成年兔的冠状动脉前降支,建立心肌梗死模型,4周后获取自体左心耳组织,急性消化分离为单细胞后分别将细胞悬液和培养液注射到移植组和未移植组梗死区内。4周后行超声心动图检查。结果4周后移植组与未移植组兔子全部存活。超声心动图检查,至移植后第4周,移植组左室功能各项指标好于未移植组。结论急性分离的自体左心耳心肌细胞移植到梗死区心肌内能够改善左室功能。     

成年犬自体骨骼肌成肌细胞移植于急性心肌梗死区的实验研究

目的观察心肌内和冠状动脉内注射法移植自体骨骼肌成肌细胞于急性心肌梗死区的生长分化特点。方法以改良成年犬骨骼肌成肌细胞培养方法进行细胞分离及扩增。结扎冠状动脉前降支中段,建立急性心肌梗死模型。分为直接注射对照、移植,冠状动脉内注射对照、移植4组,每组5只。不开通冠状动脉,分别向梗死心肌内和梗死相关冠状动脉内注射自体骨骼肌成肌细胞(1·0~1·4×108个)或等量生理盐水。移植4周后通过HE染色、PTH染色、骨骼肌特异性慢肌球蛋白抗体免疫组化染色和透射电镜寻找梗死区内存在新生肌组织的证据并观察其生长特点。结果经心肌内直接注射和冠状动脉内注射移植自体骨骼肌成肌细胞4周后,透射电镜及HE染色下均可在梗死区内找到新生幼稚肌原性细胞存在,PTH染色证实有新生的横纹肌组织形成,骨骼肌特异性慢肌球蛋白抗体免疫组化染色发现有骨骼肌原性的成熟肌组织存在;成肌细胞直接注射组内新生的肌组织排列较为密集,而冠状动脉内成肌细胞注射组内的新生肌组织排列较分散。结论通过心肌内直接注射和经梗死相关冠状动脉注射将自体骨骼肌成肌细胞移植到急性心肌梗死区后均能形成成熟的肌组织,为以骨骼肌成肌细胞进行急性心肌梗死的细胞心肌成形治疗提供了组织学依据。     

人脐带间充质干细胞移植对小型猪急性心肌梗死模型心肌细胞再生的影响

目的观察人脐带间充质干细胞移植治疗心肌梗死的可行性及机制,探讨经心外膜多点注射对小型猪急性心肌梗死模型心肌细胞再生的影响。方法无菌条件下采集足月儿的脐带,体外分离、培养、扩增人脐带间充质干细胞至第5代并以CM-Dil标记。取小型猪18例制作急性心肌梗死模型,并随机分为对照组、PBS组和移植组,每组6只。PBS组和移植组分别在梗死区注射PBS和脐带间充质干细胞。干预6周后行核素心肌灌注显像,观察梗死区灌注情况;通过免疫荧光法、Masson和TUNEL染色法观察梗死心肌中干细胞存活、增殖、分化情况和心肌纤维化、心肌细胞凋亡情况。结果与对照组及PBS组相比,移植组心肌灌注情况明显改善(P<0.01);移植后6周梗死区域可见移植的干细胞存活,其中部分向心肌和血管内皮细胞分化,亦可见固有心肌干细胞的募集与分化。TUNEL染色结果显示,移植组细胞凋亡明显减少(P<0.01)。Masson染色证实移植组的存活心肌明显增多而纤维组织明显减少(P<0.01)。结论人脐带间充质干细胞移植于心肌梗死区域后可部分存活并分化为心肌和血管组织,可促进固有心肌干细胞的募集和分化,减少细胞凋亡和组织纤维化,改善梗死区域的心肌存活情况,抑制心室重构,促进梗死心肌再生。     

经冠状动脉注射法移植成年犬自体骨骼肌成肌细胞于急性心肌梗死区的病理研究

目的观察冠状动脉内注射法移植自体骨骼肌成肌细胞到无再灌注急性心肌梗死区后的生长分化特点。方法结扎犬冠状动脉前降支中段,建立急性心肌梗死模型;杂种成年犬10只,分为对照组和经冠状动脉注射移植组,各5只。经梗死相关冠状动脉内注射自体骨骼肌成肌细胞悬液10 ml(1.0~1.4×108个)或等量生理盐水;4周后通过HE染色、PTH染色、骨骼肌特异性慢肌球蛋白抗体免疫组织化学染色和透射电镜评价移植细胞病理转归。结果经冠状动脉内注射移植自体骨骼肌成肌细胞4周后,透射电镜及HE染色下可在梗死区内找到新生幼稚肌源性细胞存在,PTH染色证实有新生的横纹肌组织形成,骨骼肌特异性慢肌球蛋白抗体免疫组织化学染色发现有骨骼肌源性的成熟肌组织存在且新生肌组织排列较分散。结论通过经梗死相关冠状动脉注射将自体骨骼肌成肌细胞移植到急性心肌梗死区后能形成成熟的肌组织。     

成年犬自体骨髓基质干细胞经冠状动脉移植在心梗后心肌组织内分化

目的　探讨经冠状动脉移植成年犬自体骨髓基质干细胞在心梗后心肌组织内的存活、分化情况。方法　结扎犬冠状动脉前降支制备心肌梗死模型 ;细胞移植组将体外培养、诱导的自体骨髓基质干细胞标记后在心肌梗死后 4周经冠状动脉植入心脏 ;对照组植入等量培养基 ;细胞移植 4周后取犬心脏 ,行组织学检查、免疫组织化学检查及电镜检查。结果　细胞移植组植入骨髓基质干细胞在心肌组织内存活 ;免疫组织化学检查结蛋白、肌钙蛋白I染色阳性 ;电镜示心肌疤痕组织中可见胞浆丰富的异源性细胞 ,圆形或椭圆形 ,细胞体积较大 ,核糖体丰富 ,线粒体较丰富 ,有肌丝样结构 ,单核。对照组心脏标本中可见疤痕组织 ;心肌细胞结蛋白染色阴性 ,肌钙蛋白I染色阳性 ;电镜未发现异源性细胞。结论　成年犬骨髓基质干细胞经冠状动脉移植后在心肌组织内存活并分化为肌源性细胞。     

心脏离体灌流装置观察细胞移植对心脏功能的影响

目的观察胚胎心肌细胞移植到大鼠急性心肌梗死区后对大鼠心脏功能的影响及其存活情况。方法100只成年大鼠随机分成2组。移植组开胸结扎大鼠冠状动脉后在梗死区内注射培养的胚胎心肌细胞悬液;对照组结扎冠状动脉后在与移植组相同的部位注射等量的细胞培养液。各组分别在移植后的48h、72h、1周、2周收集心脏标本,HE染色及抗5鄄溴脱氧尿核苷(5鄄BrdU)免疫组化染色。Langendorff心脏离体灌流装置测定移植术后第2周各组大鼠的心脏功能。结果移植组大鼠心脏左室收缩峰压(LVSP)、左室内压最大上升与下降速率( dp/dtmax,-dp/dtmax)与对照组相比明显升高,差异有非常显著意义(P<0.01),左室舒张期末压(LVEDP)明显降低,与对照组相比差异也有非常显著意义(P<0.01)。在移植组心肌梗死区内可以看到存活的胚胎心肌细胞,对照组未发现。结论胚胎心肌细胞移植能够改善大鼠的心脏功能,并且可以在大鼠的心肌梗死区内存活及分化。     

成熟心肌细胞异体移植对心肌梗死后心功能的保护作用

目的:研究异体成熟心肌细胞移植对心肌梗死后心功能的保护作用。方法:成年新西兰兔结扎冠状动脉左前降支建立心肌梗死模型,体外培养异体心肌细胞并用5溴脱氧尿核苷（BrdU）标记,将4×107/ml细胞悬液移植到急性心肌梗死区域。对照组将同量细胞培养液注射到急性心肌梗死区。细胞移植5周后超声心动图测量活体心功能,并进行组织学观察及免疫组化检测。结果:接受细胞移植组心脏功能显著优于对照组,左室重构受到抑制。细胞移植区观察到被标记心肌细胞,同时电镜下观察到心肌细胞之间存在细胞间联系。结论:移植细胞能够在宿主体内存活并与周围组织建立联系抑制左室重构,保护心脏功能。     

骨髓干细胞移植可影响心肌梗死后心肌细胞的凋亡

目的观察骨髓单个核细胞（bone marrowmononuclear cells,BM-MNCs）移植对大鼠急性心肌梗死（AMI）后心肌细胞凋亡的影响。方法健康雄性Wistar大鼠30只,随机均分为实验组和对照组。用结扎冠状动脉左前降支的方法建立大鼠AMI模型,将制备的BM-MNCs悬液和培养液分别经心外膜下植入实验组和对照组梗死心肌周围。移植术后4周末,检测心肌细胞凋亡情况及Bcl-2、Fas、FasL蛋白在心肌细胞中表达水平,并观察梗死区心肌内移植BM-MNCs及其周边区组织形态学特点。结果移植后4周末,实验组心肌细胞凋亡指数显著低于对照组（P<0.05）;与对照组相比,实验组Bcl-2蛋白吸光值显著升高（P<0.05）,Fas、FasL蛋白吸光值显著降低（P<0.05）;实验组心肌梗死区内有BrdU标记阳性的BM-MNCs存活。结论同种异体大鼠BM-MNCs移植可调节Bcl-2、Fas、FasL蛋白表达,抑制AMI后心肌细胞凋亡发生。     

脂肪间充质干细胞移植治疗兔急性心肌梗死的实验研究

目的探讨脂肪间充质干细胞(adipose tissue-derived mesenchymal stem cells,ADMSCs)移植治疗兔急性心肌梗死后心力衰竭的作用及其可能机制。方法 30只健康日本大耳白兔随机分为注射磷酸盐缓冲液的假手术组(n=10)、心肌梗死对照组(n=10)以及注射ADMSCs移植组(n=10)。结扎兔前室间支,建立急性心肌梗死动物模型,急性心肌梗死1h内将4',6-二脒-2-苯基吲哚(4',6-diamidio-2-phenylindole,DAPI)标记的第三代ADMSCs(5×106个,1mL)植入ADMSCs移植组梗死心肌,对照组及假手术组注射等量磷酸盐缓冲液液。术前及术后4周分别做超声心动图检查其心功能变化。取心肌梗死区组织作冰冻切片,荧光显微镜下验证移植后的ADMSCs是否向心肌细胞分化,苏木素-伊红染色和CD34免疫组化观察梗死区毛细血管新生情况。结果超声心动图检测证实移植后4周ADMSCs组左心室收缩末期直径、舒张末期直径与左心室重量指数均小于心肌梗死对照组[(0.72±0.04)cm vs.(0.88±0.07)cm,P0.05;(1.07±0.12)cm vs.(1.21±0.09)cm,P0.05;(1.176±0.057)g/kg vs.(1.361±0.095)g/kg,P0.05],而短轴缩短率、射血分数均大于心肌梗死对照组[31.87%±2.03%vs.28.00%±3.38%,P0.05;51.75%±3.37%vs.43.13%±3.72%,P0.05];ADMSCs移植组荧光显微镜下可以观察到DAPI标记细胞存在,并分化为心肌样细胞;CD34免疫组化染色显示ADMSCs组梗死局部毛细血管密度明显高于心肌梗死对照组[(20.00±2.65)个vs.(7.75±2.12)个,P0.05]。结论同种异体移植的ADMSCs能够在梗死心肌内存活并分化为心肌样细胞,增加梗死区血管新生,抑制心室重构、改善心肌梗死后心功能。     

经冠状动脉注射法自体骨骼肌成肌细胞移植治疗兔急性心肌梗死

目的 观察经冠状动脉注射自体骨骼肌成肌细胞（SM）移植到兔急性心肌梗死（AMI）区后的生长分化特点和疗效。方法 取日本大耳白兔45只,随机分为经冠脉注射SM移植组、对照组和假手术组,各15只。SM移植组取臀肌分离、纯化SM并体外扩增。结扎兔左冠脉前降支（LAD）,建立AMI模型。再灌注后,SM移植组经冠脉注射自体SM悬液1 ml(5×106个细胞)。对照组以相同的方法建立AMI模型,注入等量的无血清培养液。假手术组除不结扎左前降支外,其余操作均同对照组。4周后,通过HE 染色和抗5-溴脱氧尿核苷（BrDU）抗体、抗骨骼肌特异性慢β-肌凝蛋白重链（slow-MHC）抗体的免疫组化染色评价移植细胞的转归。术后24 h和4周,以超声心动图仪测量3组的左室射血分数（LVEF） 和左室短轴缩短率（FS）。结果 SM移植组在术后4周,HE染色后可在梗死区内找到新生的多核肌样细胞。抗BrdU 抗体和抗Slow-MHC抗体的免疫组化染色呈阳性。术后24 h,假手术组的LVEF 和FS 明显高于对照组和SM移植组（P<0.01）。而术后4周,与对照组比较,假手术组和SM移植组的LVEF和FS明显改善（P<0.01）。结论 经冠脉注射法移植自体SM可在AMI区存活,修复受损心肌并提高心脏的功能。     

骨髓间质干细胞移植治疗急性心肌梗死的实验研究

目的 研究同种异体骨髓间质干细胞（bone marrow mesenchymak stem cells MSCs）移植至梗死心肌后对兔的一般情况、心功能、梗死面积和血管新生的影响.方法 开胸结扎冠状动脉左前降支建立急性心肌梗死动物模型,将5-溴脱氧尿核苷（bromodeoxyuridine,BrdU）标记的MSCs注入心肌梗死区.测定各组手术前后体重和心功能并取出心脏作相关检查.结果 与急性心肌梗死组比较,MSCs组术后一般情况好,6周时体重明显增加（P＜0.05）,术后3周、6周左心室射血分数（left ventricular ejection fraction,LVEF）均明显增加（P＜0.05）,梗死面积明显缩小（P＜0.05）,毛细血管数目显著增多（P＜0.01）.MSCs组心肌梗死区可见BrdU阳性细胞,电镜下可见不成熟的心肌样细胞.结论 同种异体MSCs移植治疗急性心肌梗死除提高心功能外,尚可改善兔子的一般情况,增加体重.     

兔冠状动脉结扎后心肌间质变化及黄芪的影响

以开胸冠状动脉结扎法制备兔急性心肌梗死（AMI）模型，并设假手术对照组，各25只。AMI组中12只（随机分组）肌注黄茂注射液，另13只同期注射等量生理盐水，各2周。模型制备成功后6周再次开胸取出心脏，取左室壁心肌组织测定羟脯氨酸含量。结果：AMI组梗死区心肌羟脯氨酸含量明显高于周边区心肌及对照组（均P＜0．01），黄芪注射组与生理盐水注射组心肌羟脯氨酸含量无明显差异（P＞0．05）。结论；①胶原基质在AMI后左室重构中起一定作用；②该模型确实可靠，心肌羟脯氨酸测定可用来评价AMI模型制作方法成功与否；③黄芪无明显作用。     

同种异体移植骨髓间充质干细胞治疗大鼠心肌梗死

目的　探讨同种异体骨髓间充质干细胞 (MSCs)在梗死大鼠心脏局部存活、迁移、分化及对心功能的影响 ;明确同种异体细胞移植治疗心肌梗死 (MI)的可行性及效果。方法　雌性Wistar大鼠 3 5只 ,随机分为正常对照组、急性心肌梗死 (AMI)组及MI MSCs治疗组。分离纯化雄性Wistar大鼠骨髓MSCs ,于左冠状动脉前降支结扎后 1～ 3h植入到雌性大鼠心脏组织 ,移植后 10周检测心功能并取心脏检测各种相关指标。结果　异体大鼠MSCs经纯化后可在梗死心脏组织定居、生存 ,并与宿主心肌纤维排列方向一致 ,免疫组化检测胞质心肌特异蛋白染色阳性 ,与MI组比较 ,异体细胞移植组左室收缩压升高 (P <0 0 5) ,舒张末压明显降低 (P <0 0 1)、左心室内压最大上升和下降速率显著增快 (P <0 0 5) ,梗死边缘区心肌面毛细血管数目明显增加 (P <0 0 5) ,多功能真彩色病理图像分析系统显示MI面积缩小 (P <0 0 5)。结论　同种异体MSCs移植治疗MI可行、有效     

Improved regional left ventricular function after successful satellite cell grafting in rabbits with myocardial infarction

OBJECTIVE: To evaluate whether satellite cells injected into infarct areas in rabbits remain viable during 6 weeks follow-up and can improve cardiac function as assessed by echocardiography. METHODS: Myocardial infarction was induced in 16 New Zealand white rabbits, by ligation of the marginalis sinistra artery. Tissue from gluteus muscle biopsies was dissected into small pieces and cultured. Within 2-3 weeks the cells were expanded by 2-3 orders of magnitude and were fluorescent labeled. Single cell pellets for resuspension at >10(6)/1 ml were directly injected into the infarct areas in 8 rabbits. In 8 additional rabbits, 1 ml saline was injected (control). Regional left ventricular function was assessed weekly by 2-D echocardiography until animals were sacrificed. Analysis was performed blind and independently by two experienced echocardiographers, based on the American Society of Echocardiography scheme. RESULTS AND DISCUSSION: Six treated and five control rabbits completed the study. One week after the artery occlusion, left ventricular function scoring did not differ between groups, mean 8.7+/-1.6 vs 8.3+/-1.9 (P=0.74). At 6 weeks post-injection, echocardiographic score was significantly better in the treated group, mean 2.6+/-0.9 vs 6.9+/-2.1 (P=0.002). The treated group showed significant gradual segmental improvement between the first week up to week 6. After sacrifice, macro and microscopic transmural areas showed typical changes of myocardial infarction. Histochemical staining identified viable grafted cells in high density 6 weeks post-transplantation in all grafted hearts. CONCLUSION: Autologous satellite cells (skeletal myofiber), can be successfully grafted into rabbit hearts following myocardial infarction and may induce improved regional left ventricular function.     

内皮细胞特异性分子-1预处理干细胞用于心肌梗死治疗的实验研究

目的:探讨内皮细胞特异性分子-1(endothelial cell-specific molecule 1,ESM-1)预处理的大鼠骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BM-MSCs)植入心肌梗死(MI)大鼠后,是否能增加干细胞的存活,改善MI大鼠的心功能。方法:将用5-溴脱氧尿嘧啶核苷(Brd U)标记的BM-MSCs与ESM-1孵育预处理后,以注射器自心外膜注入SD大鼠梗死心肌周围组织。将30只SD大鼠随机分为3组,即空白组、对照组及预处理组,每组10只大鼠(n=10)。于MI后4周、干细胞移植后4周分别检测各组的超声参数:左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、室间隔厚度(IVST)和左室后壁厚度(LVPWT);用ELISA法定量检测血清脑钠尿肽(BNP)的分泌以及移植细胞的存活情况。结果:干细胞移植后4周,预处理组大鼠心脏超声检测提示LVESD、LVEDD缩小、LVEF提高,BNP含量降低,与对照组比较差异具有统计学意义(P0.01)。干细胞移植后4周,预处理组梗死周围心肌组织Brd U+的细胞数明显增多,与对照组比较差异具有统计学意义(P0.01)。结论:将ESM-1与BM-MSCs共孵育可活化BM-MSCs,促进其增殖、分化,改善心功能。     

干细胞动员剂粒细胞集落刺激因子对兔心肌结构及功能的保护作用

目的探讨骨髓干细胞动员剂粒细胞集落刺激因子(granulocyte-colony-stimulating factor,G-CSF)对实验性心肌梗死(心梗)大白兔心脏结构和功能的保护作用。方法大白兔40只,结扎冠状动脉前降支,于心电图上出现R波逐渐降低,ST段弓背向上抬高和病理性Q波时,证明心梗模型成功。将大白兔随机分成两组,每组20只。实验组于心梗模型建立后1 h给予G-CSF皮下注射,连续7 d,对照组建立心梗模型后1h仅注射等量生理盐水。术后24 h及4周心脏超声观察心功变化。处死动物,取出心脏行组织病理学分析,测定两组梗死面积的大小、毛细血管密度以及观察心肌纤维化变化。结果实验组在术后4周时射血分数(EF)、左室短轴缩短率(FS)、左室运动幅度(LVWE)、收缩末左室后壁增厚率(LVWTs)等心功能指标均较对照组有明显的改善,其中射血分数增加13％(实验组为63．40％,对照组仅为50．51％)。HE染色显示,对照组心肌纤维排列紊乱且不规则;实验组心肌纤维排列有序,梗死灶面积较对照组减小了30.2％,毛细血管密度增加了30．7％,Masson染色蓝色的胶原纤维明显少于对照组。结论急性心梗时给予G-CSF,可有效增加梗死区及周围毛细血管密度,缩小梗死面积,减少胶原纤维形成,稳定心脏结构及改善心功能。骨髓干细胞动员剂为急性心肌梗死的内科治疗开辟了一条新途径。     

A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease

OBJECTIVE: Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI). METHODS: BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, cardiac function was analyzed with the use of a conductance catheter, and histopathologic analysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI. RESULTS: Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI. CONCLUSION: The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease.     

In-Vivo Electrophysiological Study in Mice with Chronic Anterior Myocardial Infarction

Introduction: An increasing number of genetically altered mice with specific molecular cardiac defects are being assessed by electrophysiological studies and ECG monitoring. This approach should allow for the identification of critical genes involved in the arrhythmogenesis in myocardial infarction. Therefore it was the aim of this study to establish a standard for the in-vivo electrophysiological characteristics in the mouse model of chronic anterior myocardial infarction. Methods and Results: Using a minimized, invasive, in-vivo electrophysiological study, surface ECG parameters, sinus node function, atrial, atrio-ventricular and ventricular conduction and ventricular repolarization, and enhanced vulnerability to atrial and ventricular arrhythmia were studied in 20 wild-type C57BL/6 mice either under control or 11 weeks after large anterior myocardial infarction induced by ligation of the left anterior descending coronary artery. Telemetric ECG recording was performed in the same animals at baseline unrestrained, conscious condition to study surface ECG parameters, heart rate variability and the prevalence of supraventricular and ventricular arrhythmia. During electrophysiological study, infarcted mice showed an 81% increase of the angle of the QRS axis (p < 0.001) and a prolongation of the P wave by 23% (p = 0.01), the QRS complex by 39% (p = 0.001), the QT interval by 23% (p<0.05), the QT_c interval by 30% (p < 0.005) and the JT_c interval by 31% (p < 0.05) in comparison to control animals. Furthermore, there was a prolongation of the atrio-ventricular interval by 28% (p < 0.0005) and the atrio-ventricular functional refractory period by 26% in infarcted animals (p < 0.05), and inducibility of ventricular tachycardia in 4 of 6 infarcted versus in none of control animals (0 < 0.01). During telemetric ECG recording, there was a marked increase in ventricular ectopic activity in infarcted mice in comparison to controls (p < 0.05). Heart rate and time- and frequency-domain of heart rate variability were not significantly different in both groups (p > 0.05, respectively). Conclusions: The mouse model of chronic anterior myocardial infarction is associated with significant atrial and ventricular conduction disturbances and vulnerability to ventricular arrhythmia and thus may provide a highly valuable tool to study molecular determinants of arrhythmogenesis in myocardial infarction.     

慢性缺血性心力衰竭模型制备方法的对比研究

目的探讨冷冻左心室前壁与结扎前降支两种方法诱导大鼠心肌梗死后制作慢性心力衰竭模型的对比研究。方法选择8～10周龄SD健康大鼠120只,随机分为冷冻组(50只),结扎组(50只)、假手术组(20只)。手术后4周行心电图、心功能检查,取心脏组织行TTC、HE染色并观察其死亡率。结果手术后4周冷冻组大鼠死亡率为32%低于结扎组48%。与假手术组比较,冷冻组、结扎组大鼠心电图显示为心肌梗死,LVEF、左心室短轴缩短率明显降低,左心室舒张末直径明显升高,差异有统计学意义(P<0.01),冷冻组和结扎组大鼠心肌切片、TTC染色可见100%梗死区;梗死区HE染色主要为瘢痕组织,假手术组未见心肌梗死。结论冷冻法诱导的心力衰竭模型在心功能、心肌梗死面积等方面等同于结扎法,且死亡率明显减低,冷冻左心室前壁诱导大鼠心肌梗死后慢性心力衰竭模型较结扎法更好。