急性缺血心肌无针喷射双生长因子藻酸盐水凝胶的孔道效应

目的 采用无针喷射心肌打孔,观察无针喷射生长因子藻酸盐水凝胶的孔道效应.方法 制备包裹血管内皮细胞生长因子和血小板源性生长因子藻酸盐水凝胶.成功建立兔心肌梗死模型后,随机分成3组:盐水组、凝胶组和生长因子凝胶组,随后行无针喷射心肌打孔,术中采用超声诊断仪监控无针喷射过程.术后8周,心脏超声造影观察孔道效应,造影后2 d进行HE染色及Masson染色.结果 肉眼观察可见白色糊状凝胶填充于孔道内部.超声诊断仪可全程监控无针喷射过程.心脏超声造影结果显示生长因子凝胶组超声微泡造影剂可沿孔道直接灌注心肌,其余两组未见造影剂经心室腔直接灌注心肌.HE染色结果显示生长因子凝胶组在心肌梗死周边无针喷射区可观察到孔道形成,其余两组孔道已闭合.Masson染色结果显示生长因子凝胶组孔道外壁包绕较多染有蓝色的胶原纤维,而孔道维持开放,其余两组孔道被染有蓝色的胶原纤维填充.结论 无针喷射包裹生长因子藻酸盐水凝胶可于心肌梗死周边区建立孔道,实现血液经心室腔沿孔道直接灌注缺血心肌.     

心肌内控制释放碱性成纤维细胞生长因子促进血管再生的作用

背景实验研究表明,生长因子能促进心肌血管再生,采用纤维蛋白胶心肌内控制释放碱性成纤维细胞生长因子的血管再生作用和机制尚不明确.目的评价纤维蛋白胶心肌内控制释放碱性成纤维细胞生长因子对急性心肌梗死犬局部相关血管生长因子表达与细胞增殖水平的影响,探讨心肌内控制释放碱性成纤维细胞生长因子对血管再生的治疗作用.设计完全随机分组设计,对照实验.单位首都医科大学附属北京安贞医院心内科、华中科技大学同济医学院附属协和医院心内科和上海新兴血液制品研究所.材料实验于2001-06/2003-03先后在华中科技大学同济医学院附属协和医院外科动物实验室和解放军总医院医学实验动物中心完成.选用清洁级健康成年杂种犬12只,雌雄不拘.随机将犬分为2组激光心肌血运重建组和碱性成纤维细胞生长因子组,每组6只.方法①将12只成年健康杂种犬于麻醉开胸后暴露心脏,结扎左前降支制作急性心肌梗死模型.动物随机分为2组激光心肌血运重建组于急性心肌梗死30 min后行透壁心肌打孔;碱性成纤维细胞生长因子组则于急性心肌梗死30 min后行非透壁心肌打孔,并随后向孔道内注射含有碱性成纤维细胞生长因子的纤维蛋白胶.②术后第8周,采用免疫组织化学染色和HPIAS-2000型彩色病理图文分析系统免疫组织化学分析程序分析缺血心肌局部血管内皮生长因子、转化生长因子β1和增殖细胞核抗原表达水平的变化.③均数间比较采用非配对t检验或方差分析.主要观察指标激光心肌血运重建组和碱性成纤维细胞生长因子组梗死区心肌血管内皮生长因子、转化生长因子β1和增殖细胞核抗原免疫组织化学染色的定量分析.结果激光心肌血运重建组和碱性成纤维细胞生长因子组分别有5只和6只犬进入结果分析,免疫组织化学定量分析发现,碱性成纤维细胞生长因子组梗死区心肌血管内皮生长因子、转化生长因子β1和增殖细胞核抗原染色的显色面积均高于激光心肌血运重建组(t=-7.505,-2.690与-6.895,P＜0.05),碱性成纤维细胞生长因子组增殖细胞核抗原染色的平均吸光度也高于激光心肌血运重建组(t=-5.271,P＜0.05).结论心肌内控制释放碱性成纤维细胞生长因子能提高缺血心肌局部相关血管生长因子(如血管内皮生长因子、转化生长因子β1等)的表达水平,增强细胞增殖,从而促进血管再生.     

心肌内双层多孔生物可降解性药物缓释支架的制备

目的：制备心肌内双层多孔生物可降解性药物缓释支架,评估其对透室壁性心肌血管重建术后心肌孔道的作用效果。方法：以聚己内酯为材料,以牛血清白蛋白为模型药物,以聚乳酸-聚乙醇酸共聚物为药物载体,制备成生物可降解性药物缓释支架。采用考马斯亮蓝试剂法对支架上牛血清白蛋白含量及体外释放量进行测定,万能材料测定仪测定支架的力学性能。制备猪慢性心肌局部缺血模型,体内评估该支架在透室壁性心肌血管重建术后对心肌孔道的作用效果。结果：该支架牛血清白蛋白携带量为每支架10mg,30d后牛血清白蛋白释放量达80%,支架压缩80%时承受的应力为1.2MPa,在透室壁性心肌血管重建后可保持心肌孔道通畅。结论：成功制备心肌内双层多孔生物可降解性药物缓释支架,能承受心肌压力并达到缓慢控制释放药物的效果,可维持透室壁性心肌血管重建后的心肌孔道通畅。     

心肌内控制释放碱性成纤维细胞生长因子促进血管再生的作用

背景：实验研究表明，生长因子能促进心肌血管再生，采用纤维蛋白胶心肌内控制释放碱性成纤维细胞生长因子的血管再生作用和机制尚不明确。 目的：评价纤维蛋白胶心肌内控制释放碱性成纤维细胞生长因子对急性心肌梗死犬局部相关血管生长因子表达与细胞增殖水平的影响，探讨心肌内控制释放碱性成纤维细胞生长因子对血管再生的治疗作用。 设计：完全随机分组设计，对照实验。 单位：首都医科大学附属北京安贞医院心内科、华中科技大学同济医学院附属协和医院心内科和上海新兴血液制品研究所。 材料：实验于2001-06／2003-03先后在华中科技大学同济医学院附属协和医院外科动物实验室和解放军总医院医学实验动物中心完成。选用清洁级健康成年杂种犬12只，雌雄不拘。随机将犬分为2组：激光心肌血运重建组和碱性成纤维细胞生长因子组，每组6只。 方法：①将12只成年健康杂种犬于麻醉开胸后暴露心脏，结扎左前降支制作急性心肌梗死模型。动物随机分为2组：激光心肌血运重建组于急性心肌梗死30min后行透壁心肌打孔；碱性成纤维细胞生长因子组则于急性心肌梗死30min后行非透壁心肌打孔，并随后向孔道内注射含有碱性成纤维细胞生长因子的纤维蛋白胶。②术后第8周，采用免疫组织化学染色和HPIAS-2000型彩色病理图文分析系统免疫组织化学分析程序分析缺血心肌局部血管内皮生长因子、转化生长因子β1和增殖细胞核抗原表达水平的变化。③均数间比较采用非配对t检验或方差分析。主要观察指标：激光心肌血运重建组和碱性成纤维细胞生长因子组梗死区心肌血管内皮生长因子、转化生长因子β1和增殖细胞核抗原免疫组织化学染色的定量分析。 结果：激光心肌血运重建组和碱性成纤维细胞生长因子组分别有5只和6只犬进入结果分析，免疫组织化学定量分析发现，碱性成纤维细胞生长因子组梗死区心肌血管内皮生长因子、转化生长因子β1和增殖细胞核抗原染色的显色面积均高于激光心肌血运重建组（t=-7．505,-2．690与-6．895，P〈0．05）。碱性成纤维细胞生长因子组增殖细胞核抗原染色的平均吸光度也高于激光心肌血运重建组（t=15．271。P〈0．05）。 结论：心肌内控制释放碱性成纤维细胞生长因子能提高缺血心肌局部相关血管生长因子（如血管内皮生长因子、转化生长因子β1等）的表达水平，增强细胞增殖，从而促进血管再生。     

KTP激光心肌打孔联合血管内皮生长因子转染对犬心功能的影响

目的探讨在KTP激光心肌打孔(TMLR)基础上联合血管内皮生长因子(VEGF)基因转染治疗对急性心肌梗死犬心功能的影响。方法家犬18只,随机均分为单纯心肌梗死组(SMI组)、TMLR组和TMLR+转VEGF基因组(TMLR+VEGF组)。结扎左前降支中段造成急性心肌梗死,TMLR组在梗死区以KTP激光行TMLR,TMLR+VEGF组在TMLR后于孔道边缘心肌内注射PAdTrack/VEGF165裸质粒2mg。术后8周,应用M型、二维及多普勒组织成像(DTl)技术检测左室局部和整体功能。结果①反映左心室整体收缩功能的指标,在SMI组、TMLR组和TMLR+VEGF组依次增大(P<0·05),并且TMLR+VEGF组分别与SMI组、TMLR组比较,差异均有显著性(P<0·05);②反映左室局部功能的主要指标,在以上三组依次增大(P<0·05);③反映心脏舒张功能的指标,在以上三组依次增大,但三组之间无统计学差异意义(P>0·05)。结论KTP激光心肌打孔联合VEGF165基因治疗,能增强KTP激光心肌打孔血运重建的疗效,进一步改善梗死心肌局部功能和整体收缩功能,但对整体舒张功能无明显影响。     

心肌梗死局部注射壳聚糖水凝胶材料的存留和降解

背景:研究发现壳聚糖水凝胶可促进受损组织新生血管生成,修复损伤细胞和组织。目的:观察心肌梗死部位局部注射壳聚糖水凝胶材料的存留和降解及其对心脏功能的保护作用。方法:结扎Wistar大鼠冠状动脉左前降支致心肌梗死30min后,随机抽签法分为壳聚糖水凝胶注射组、心肌梗死模型组、PBS注射组。术后1,2,4周使大鼠心脏停留在舒张期行心肌组织学检查,术后4周进行心电图、心脏超声检测,并进行大鼠颈动脉插管,检测心脏功能和心室内压。结果与结论:壳聚糖水凝胶注射1,2周后在心肌组织中有明显存留,4周后已降解吸收,无明显残留。注射4周后心脏超声、心室血流动力学及心室内压检测结果表明,壳聚糖水凝胶注射组心脏功能明显好于心肌梗死模型组、PBS注射组,而心肌梗死模型组和PBS注射组之间没有明显的区别。说明以壳聚糖为支架材料,应用配制的可注射性液态支架进行心肌梗死局部注射治疗,注射4周后无明显残留,保护和改善了心脏功能,适宜作为可注射性组织工程化心肌的支架材料。     

心肌梗死局部注射壳聚糖水凝胶材料的存留和降解

背景：研究发现壳聚糖水凝胶可促进受损组织新生血管生成,修复损伤细胞和组织。目的：观察心肌梗死部位局部注射壳聚糖水凝胶材料的存留和降解及其对心脏功能的保护作用。方法：结扎Wistar大鼠冠状动脉左前降支致心肌梗死30min后,随机抽签法分为壳聚糖水凝胶注射组、心肌梗死模型组、PBS注射组。术后1,2,4周使大鼠心脏停留在舒张期行心肌组织学检查,术后4周进行心电图、心脏超声检测,并进行大鼠颈动脉插管,检测心脏功能和心室内压。结果与结论：壳聚糖水凝胶注射1,2周后在心肌组织中有明显存留,4周后已降解吸收,无明显残留。注射4周后心脏超声、心室血流动力学及心室内压检测结果表明,壳聚糖水凝胶注射组心脏功能明显好于心肌梗死模型组、PBS注射组,而心肌梗死模型组和PBS注射组之间没有明显的区别。说明以壳聚糖为支架材料,应用配制的可注射性液态支架进行心肌梗死局部注射治疗,注射4周后无明显残留,保护和改善了心脏功能,适宜作为可注射性组织工程化心肌的支架材料。     

急性心肌梗死早期患者血清中可溶型ST2水平及其与心肌活性的关系

目的探讨急性心肌梗死患者早期血清可溶性ST2(sST2)水平及其与心肌活性的关系。方法采用ELISA法检测30例发病12 h以内的非ST段抬高型心肌梗死(NSTEMI)患者血清sST2水平,于发病后第7天行心脏磁共振检查并根据磁共振结果将患者分为透壁增强组、非透壁增强组和混合组。于7¹4 d行PCI术,并于术后6个月再次行心脏磁共振检查评估心肌活性,观察指标包括梗死心肌质量、左心室射血分数及室壁运动异常评分在术前及术后的变化及其与心肌梗死早期血清sST2水平的关系。结果透壁增强组血清sST2的水平较之非透壁增强组及混合组明显升高(P<0.05),混合组较非透壁增强组高(P<0.05);梗死心肌质量及室壁运动异常评分在3组患者PCI术后均减少,梗死心肌质量在非透壁增强组及混合组中减少有统计学差异(P<0.05),室壁运动异常评分在非透壁增强组降低显著(P<0.05);左心室射血分数在3组患者PCI术后均增加,在非透壁增强组及混合组中增加有统计学差异(P<0.05)。心肌梗死早期血清sST2水平与PCI术前及PCI术后6个月的心肌活性相关。结论急性心肌梗死早期血清中sST2的水平可反映心肌受损情况并可预测心肌梗死7 d PCI术前及PCI术后6个月的心肌活性。     

冠状动脉病变与供血心肌损伤程度的对照分析

目的探讨心肌灌注MRI所示梗死心肌体积及分型与供血冠状动脉狭窄程度和位置的关系.方法 47例急性心肌梗死患者急诊接受冠状动脉造影及介入治疗,其后6～8周行心肌延迟灌注MR扫描,测定梗死心肌相对体积并分型.结果 22例患者单支冠状动脉完全闭塞,25例患者多支冠状动脉多处狭窄;MRI示前者延迟强化灶体积显著大于后者,以透壁型为主,后者以非透壁型为主.结论单支冠状动脉近端闭塞较多支冠状动脉多处狭窄更易造成大范围透壁心肌梗死.     

兔心肌梗死后细胞因子及心肌胶原纤维含量变化与别嘌呤醇的影响

目的:观察别嘌呤醇对兔心肌梗死后血浆和心肌细胞因子水平及心功能、心室重构的影响。方法:实验于2004-09/2005-06在南昌大学第二附属医院动物试验室完成。①分组和造模:18只新西兰大白兔随机分为假手术组、模型组和别嘌呤醇组,每组6只,后2组采用液氮冷冻法制造心肌梗死模型。②给药:术后别嘌呤醇组每日给予别嘌呤醇(广州彼迪药业有限公司)40mg/kg,另2组给予等量安慰剂。③观察指标:梗死后4周进行超声检查和血流动力学测定;同时采用酶联免疫法检测各组血浆及心肌组织白细胞介素6和肿瘤坏死因子α水平;VG染色检测各组兔心肌间质胶原含量。结果:经补充后18只兔进入结果分析。①心脏超声检查结果:与假手术组相比,其他2组兔室腔明显增大(P<0.01),室壁运动明显减弱,左室射血分数明显降低(P<0.01);别嘌呤醇组和模型组相比,室腔明显减小(P<0.01),室壁运动明显增强,左室射血分数明显升高(P<0.01)。②血流动力学检测结果:与假手术组相比,其他2组兔左室舒张末压显著升高(P<0.01),左室收缩末压及左室内压上升/下降最大速率显著降低(P<0.01);别嘌呤醇组和模型组相比其左心室的舒、缩功能均等到明显改善(P<0.01)。③细胞因子检测结果:其他2组血浆及心肌组织和白细胞介素6和肿瘤坏死因子α水平都显著高于假手术组(P<0.01),而别嘌呤醇组低于模型组(P<0.01)。④心肌间质胶原含量检测结果:模型组和别嘌呤醇组含或不含小血管视野胶原容积百分比都显著高于假手术组(P<0.01),而别嘌呤醇组低于模型组(P<0.01)。结论:别嘌呤醇可以改善兔心肌梗死后血浆及心肌组织细胞因子水平,别嘌呤醇改善心功能和抑制心室重构可能与其降低细胞因子水平的作用相关。     

碱性成纤维细胞生长因子缓释支架联合骨髓间质干细胞治疗猪心肌梗死的心肌SPECT显像

目的 评价心肌SPECT显像对碱性成纤维细胞生长因子(b-FGF)缓释支架联合骨髓间质干细胞(BM-MSCs)移植治疗中国实验用小型猪急性心肌梗死的价值.方法 中国实验用小型猪18头,按完全随机法分为3组:机械打孔+空白支架(对照组)、机械打孔+b-FGF支架(单纯治疗组)、机械打孔+b-FGF支架+BM-MSCs(联合治疗组).所有猪左前降支均被结扎制作心肌梗死模型.3组均在梗死区及周边区机械打孔并分别埋入空白支架、b-FGF支架、b-FGF支架+BM-MSCs;术后行心肌SPECT显像检测心肌血流的改变,同时还进行超声心动图、免疫组化检查.结果 术后6周,治疗组梗死心肌质量差值、短轴缩短率、新生血管密度均高于对照组(P<0.05),且联合治疗组高于单纯治疗组(P<0.05).结论 b-FGF缓释支架联合BM-MSCs能够改善心肌梗死区域血流、促进血管生长、提高心功能;心肌SPECT显像是评估碱性成纤维细胞生长因子缓释支架联合骨髓间质干细胞治疗急性心肌梗死效果有价值的方法.     

心肌再血管化机制的对比实验研究

目的观察研究钬激光和True-cut活检针心肌再血管化近、远期的机制和效果。方法利用经静脉注射造影剂对犬缺血心肌模型进行心肌超声微泡造影。结果部分结扎犬的冠状动脉前降支,建立缺血模型后,缺血区超声微泡密度明显降低,分别用2种方法再血管化后,2组犬缺血区超声微泡密度较缺血时均明显增加,接近其缺血前的微泡密度;再血管化区超声微泡较其他部位提前显影。远期超声微泡检查显示心肌灌注较急性缺血时也有一定改善。结合组织学方法发现,远期心肌灌注的改善得益于隧道周围新生循环结构如心肌窦和新生血管的增加。结论钬激光和True-cut活检针隧道均可即刻使缺血心肌灌注改善,并逐渐闭塞,新生循环结构使缺血区得到有限的灌注。应用新一代经静脉注射造影剂超声心肌微泡造影结合组织学方法可作为研究心肌再血管化机制的可靠手段。     

Lasers in the treatment of ischaemic heart disease

Mounting evidence showing that transmyocardial laser revascularization (TMR) is a safe and effective treatment for angina pectoris arrives just as an increasing number of patients who have undergone angioplasty and coronary artery bypass grafting experience failure with time. TMR, nevertheless, remains controversial. It appears to relieve the symptoms without treating the underlying atherosclerotic disease, and its method of action is unproven. Like angioplasty and coronary bypass, TMR in fact offers palliation rather than a cure for atherosclerotic heart disease. The most sensible current formulations of the therapeutic mechanism of TMR posit a reconfiguration of the microcirculation, with blood shunted from epicardial to endocardial areas. These unresolved issues notwithstanding, TMR benefits patients with end-stage coronary disease and represents a pioneering effort to remodel the microcirculation of patients with arteriosclerotic occlusive disease.     

Lasers in the treatment of ischaemic heart disease

Mounting evidence showing that transmyocardial laser revascularization (TMR) is a safe and effective treatment for angina pectoris arrives just as an increasing number of patients who have undergone angioplasty and coronary artery bypass grafting experience failure with time. TMR, nevertheless, remains controversial. It appears to relieve the symptoms without treating the underlying atherosclerotic disease, and its method of action is unproven. Like angioplasty and coronary bypass, TMR in fact offers palliation rather than a cure for atherosclerotic heart disease. The most sensible current formulations of the therapeutic mechanism of TMR posit a reconfiguration of the microcirculation, with blood shunted from epicardial to endocardial areas. These unresolved issues notwithstanding, TMR benefits patients with end-stage coronary disease and represents a pioneering effort to remodel the microcirculation of patients with arteriosclerotic occlusive disease.     

Transmyocardial revascularization: peril and potential

Transmyocardial laser revascularization is a technique for the treatment of patients with chronic angina pectoris that is refractory to medical therapy and who are not eligible for surgical intervention. Percutaneous myocardial revascularization is a less-invasive catheter-based procedure that has been adapted from transmyocardial laser revascularization. Six prospective randomized clinical trials have been performed with transmyocardial laser revascularization and 5 have been performed using percutaneous myocardial revascularization. All of the transmyocardial laser revascularization and 4 of the percutaneous myocardial revascularization studies showed a significant improvement in angina class; however, results for improved survival, increased exercise tolerance, improved ejection fraction, and improved myocardial perfusion were less definitive. Transmyocardial laser revascularization has significant potential for morbidity and mortality. This article summarizes the results of the randomized trials, explains the current theories for the mechanism of transmyocardial laser revascularization, and discusses its current role in treatment for patients, considering the evidence that currently exists.     

Transmyocardial and percutaneous myocardial revascularization: current and future role in the treatment of coronary artery disease.

Transmyocardial revascularization (TMR) is a new treatment modality under evaluation in patients with severely symptomatic, diffuse coronary artery disease, in whom the potential for medical or interventional management has been exhausted. Preliminary clinical trials show improved ischemic symptoms within the first 3 months in about 70% of TMR-treated patients. The original proposed mechanism of surgical or catheter-based TMR (percutaneous myocardial revascularization [PMR]) was that channels mediate direct blood flow between the left ventricular cavity and ischemic myocardium. However, several alternative explanations for the clinical success of TMR have recently been suggested, including improved perfusion by angiogenesis, an anesthetic effect by nerve destruction, and a potential placebo effect. This article reviews the clinical role of TMR/PMR, its possible pathophysiologic mechanisms, and its controversies. It provides an overview of the actual scientific and clinical status of TMR and details future directions.     

Extent of myocardial tissue damage during transmyocardial laser revascularization with the CO2 Heart Laser.

OBJECTIVE AND BACKGROUND: Transmyocardial laser revascularization (TMR) is the only surgical treatment for patients with severe diffuse coronary artery disease, who are not candidates for bypass grafting or percutaneous angioplasty. However, vaporization of tissue during the creation of channels leads to a certain loss of viable myocardium during every TMR procedure. METHODS: We analyzed serum levels of creatine kinase and creatine kinase MB subtype in 163 patients after sole TMR with a CO2 laser (wave length 10.6 microm, 800-watt power). The control group consisted of 35 consecutive CABG patients and 30 consecutive redo-CABG patients. Additionally, in the TMR group we measured echocardiographically the left ventricular ejection fraction before and after TMR. We recorded the total amount of laser energy applied, average and maximum energy per channel, and the number of created channels, in order to calculate the correlation between these parameters and postoperative enzyme levels or changes in the LVEF. RESULTS: After TMR, we measured higher creatine kinase levels compared to those in CABG patients (607.8+/-558.4 U/L vs. 285.0+/-292.3 U/L, p < 0.01). The relative proportion of CK-MB of total CK, however, was significantly lower after TMR, compared to that of the control group (4.5+/-3.0% vs. 10.1+/-6.4%, p < 0.01). Patients with a pronounced postoperative increase in CK-MB levels or a higher percentage of CK-MB of total CK also after TMR operations show a decline in left ventricular contractility. In the laser group, the maximum enzyme levels were detected significantly later than in the control group (25.0+/-19.4 h postoperatively vs. 8.7+/-9.1 h, p < 0.01). There was no significant correlation between the technical laser parameters or the number of created channels and the percentage of CK-MB of total CK or changes in left ventricular ejection fraction. CONCLUSIONS: CO2 laser TMR does not result in significant injury to the myocardium. Cardiac enzymes play an important role in the detection of perioperative myocardial infarction in TMR patients.     

Transmyocardial laser revascularization: a review

There is an increasing number of treatment alternatives available for those with ischemic heart disease. Surgical procedures are more sophisticated, a wide array of medications are available, and numerous catheter techniques have evolved to treat patients with coronary artery disease. Technical advances and lifestyle modifications have contributed to a decline in age-adjusted death rates. Despite these advances, there remain a significant number of patients with myocardial ischemia who are not candidates for conventional therapies. Transmyocardial laser revascularization may be a viable adjunct or alternative therapy. In performing this technique, channels are made, from the epicardial surface of the heart through the left ventricle and endocardium, with the CO 2 laser. Perfusion is from the blood supply in the left ventricle via the channels. Postoperative thallium stress tests and left ventriculography indicate that the channels remain patent and protect the ischemic muscle. Experimental and early clinical results of transmyocardial laser revascularization suggest that a group of patients may benefit from this treatment.