激光心肌血管重建术后激光管道的形态学观察

为临床研究和应用激光心肌血管重建术提供解剖学基础,本文在１６只杂交犬的心肌梗塞模型上,行ＣＯ２激光心肌打孔。术后３或６个月取出心脏,观察不同时间未铸型及铸型激光心肌管道的形态特征。结果表明激光管道心内膜侧管径大于心外膜侧,管道多呈锥形。     

激光心肌血管重建术长期实验观察

本实验旨在研究激光心肌血管重建术二种打孔方法对激光孔远期通畅的影响。方法３６只犬结扎左前降支获得急性心肌缺血动物模型,在缺血区随机分为Ａ、Ｂ二区,Ａ区采用“Ｍｉｒｈｏｓｅｉｎｉ”法,Ｂ区采用“滤波片”法打孔,术后４小时、０．５月、１个月、３个月、６个月取出心脏,通过病理学及微血管铸型判断激光孔是否通畅。结果术后６个月“Ｍｉｅｈｏｓｅｉｒｉ”法通畅率３８％,“滤波片”法７０％,术后３６个月激光孔仍通畅。结论“滤波片”法优于“Ｍｉｒｈｏｓｅｉｎｉ”法,二种打孔方法对心肌缺血有长期改善作用。     

100WCO2激光心肌血管再造术的实验研究

本文给出了利用１００ＷＣＯ２激光心肌血管再造术动物实验研究结果。激光器采用１００ＷＣＯ２激光,经光关节臂传输和会聚,激光孔径０．２５～０．５ｍｍ,孔间距离５ｍｍ,照射时间０．３秒,利用附加“滤波器”激光打孔技术可减轻心脏的热损伤。结果表明,在正常心肌上打孔,孔周２７０μｍ以外的心肌基本上不受损伤;高功率密度的激光束心肌打孔能够改善心肌微循环,可以明显改善打孔区的心肌缺血程度。实验犬术后六个月铸型实验证实了激光孔道仍然存在,术后三年病理切片检查充分说明了激光孔道仍然保持畅通     

激光照射血液疗法中的组织光学研究及其应用

本文从组织光学的角度 ,对激光照射血液疗法中的发展现状与存在问题进行分析 ,提出该领域应开展的若干研究内容。本文开展了激光照射血液疗法所涉及的若干组织光学研究。获得了中国人血液的吸收系数、散射系数、各项异性因子、全衰减系数等 ;研究获得了人血管的若干光学参数。通ＭｏｎｔｅＣａｒｌｏ模拟计算 ,以及实验测试结果 ,分别从理论与实际上分析对比了激光血管内照射时 ,光在人体血管、血液中的分布情况 ,以及不同的激光入射角 ,发散角 ,不同的血管直径等因素对激光血液照射的影响。根据对应的组织光学的研究结果 ,文中还讨论并提出…     

开搏通对游泳大鼠心肌肥大的影响

为了明确开搏通对运动性心肌肥大的作用。本实验采用游泳训练引起的大鼠心肌肥大模型,应用放射免疫及生化等方法对心肌肥大及心脏肾素－血管紧张素系统（Ｒ－Ａ－Ｓ）的变化进行了初步研究。观察到游泳五周时,大鼠心重／体重比值（Ｈ／Ｂｗｔ）显著升高,同时心肌血管紧张素Ⅱ（ＡｎｇⅡ）及心肌血管紧张素转换酶（ＡＣＥ）也明显升高。而服用开搏通的游泳大鼠心肌ＡｎｇⅡ,ＡＣＥ较单纯游泳组低,但心重／体重比值却升高。上述结果提示开搏通能抑制运动所致心肌ＡｎｇⅡ升高,但不能防止运动引起的心肌肥大。     

Myocardin在血管平滑肌细胞表型转化中的作用

近年来大量的实验研究表明,血管平滑肌细胞(VSMCs)的增殖和迁移是各种血管疾病,包括动脉粥样硬化斑块形成、高血压、血管成形术后再狭窄等的病理基础。而血管平滑肌细胞的表型转化在其增殖和迁移中发挥着重要的作用。心肌素(myocardin)是迄今为止发现的最关键的促血管平滑肌细胞分化的转录因子,能有效激活平滑肌细胞(SMCs)的分化程序。近年来,人们对心肌素在平滑肌细胞表型转化过程中的功能进行了深入研究。现对血管平滑肌细胞的表型转化以及心肌素在血管平滑肌转化中的作用作一综述。     

一种新的激光心肌打孔方法研究

本实验旨在研究一种新的ＣＯ２激光心肌打孔方法改善急性心肌缺血。８只犬结扎冠状动脉左前降支获得急性心肌缺血动物模型,在缺血区随机分为Ａ、Ｂ二区,Ａ区不打孔作为自身空白对照,Ｂ区在心脏跳动情况下被激光打孔,在打孔时将滤波片放在光关节臂和心脏表面之间。结果：（１）心外膜电图,∑ＳＴ,打孔后３０分钟,Ａ、Ｂ二区差值具有显著意义（Ｐ＜０．０２０）;ＮＳＴ,打孔后２０分钟,Ａ、Ｂ二区比较有显著差异（Ｐ＜０．００５）。（２）病理学,冰冻切片Ｈ．Ｅ染色,激光孔没有碳化层,水肿层仅为５０ｕｍ,激光孔和周围血管相通,血管内可见血液的各种有形成份。实验表明,在形成急性心肌缺血情况下及时采用这种新的心肌打孔方法进行打孔能再造一套有效的血液供应系统,明显改善缺血程度,缩小缺血范围。     

血管生成在冠心病治疗中的应用进展

随着心血管治疗药物与技术方法的进步 ,冠心病患者的生活质量有所改善 ,但是晚期冠心病 (ｅｎｄ ｓｔａｇｅｃｏｒｏｎａｒｙｈｅａｒｔｄｉｓｅａｓｅ)患者对于常规药物治疗反应较差 ,而且由于病人年龄偏大或冠状动脉的弥漫性病变等原因而不适于进行传统的心肌血管重建术 ,如冠状动脉搭桥术 (ｃｏｒｏｎａｒｙａｒｔｅｒｙｂｙｐａｓｓｇｒａｆｔ ,ＣＡＢＧ)和经皮穿刺冠状动脉腔内血管成型术 (Ｐｅｒ ｃｕｔａｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌｃｏｒｏｎａｒｙａｇｉｏｐｌａｓｔｙ ,ＰＴＣＡ )等 ,因此如何改善晚期冠心病患者的生活质…     

中药促缺血心肌血管新生机制研究进展

中药在缺血性心脏病的治疗方面具有重要作用,能够缓解症状并改善预后,促血管新生可能是其发挥作用的机制之一。已证实通过促进血管新生,可使心肌梗死面积缩小,减少细胞坏死和凋亡,改善心功能等,但其机制尚需进一步明确。目前中医药在促进梗死心肌血管新生研究方面已经取得了一定的成果,研究发现,大量中药单体、方剂及中成药具有促进血管新生作用。随着对中药促血管新生研究的不断深入,其机制的研究亦愈趋广泛,已深入到细胞及分子水平:涉及骨髓干细胞,促进血管生长的因子及其受体(血管内皮细胞生长因子、碱性成纤维细胞生长因子、胰岛素样生长因子等),抑制血管生长的因子(血管抑素、内皮抑素)及Akt/NOS/NO等通路。本文就相关研究回顾中药对缺血心肌血管新生影响并对机制进行探讨。     

关于“弱激光血管内照射疗法”的几个问题

本文从：１．关于“弱激光血管内照射疗法（ＩｎｔｒａｖａｃｕｌａｒＬｏｗ－Ｒｅａｃｔｉｏｎ－ｌｅｖｅｌＬａｓｅｒＩｒｒａｄｉａｔｉｏｎＴｈｅｒａｐｙＩＬＬＬＴ）的中、英文名称问题。２．该疗法引入我国的历史回顾。３．该疗法的临床效果与基础研究。４．该疗法与光量子疗法（ＵＢＩ）的比较。５．该疗法在我国面临的问题及展望等五个方面以较详实的材料对以Ｈｅ—Ｎｅ激光为代表的弱激光血管内照射疗法客观地进行阐述,并以笔者的研究实践及其认识为基础提出看法以期探讨,从而澄清目前国内对该疗法尚存在的某些混乱状况与模糊认识,使其作为弱激光的一种很有前途的临床疗法能走上健康发展的道路。     

Cellular Destruction Following Transmyocardial Laser Revascularization (TMR)

Summary During transmyocardial revascularization, cellular destruction of cardiomyocytes occurs as a result of the high-energy laser. However, the features of myocardial cellular destruction are unclear. The present study was undertaken to examine the structural characteristics of cell death in the myocardium following transmyocardial revascularization. Myocardial specimens from 3 male patients who had died within 11 days following laser revascularization were collected within 1 h of death and were analyzed by immunohistochemistry and electron microscopy. For immunohistochemistry, antibodies to pro-apoptotic proteins CPP32 and BAX were used. Immunohistochemical examination demonstrated the presence of cells expressing both CPP32 and BAX along the laser channel. Electron microscopic analysis revealed that the lining surface of laser channels consisted of condensed acellular debris and dead cells. No endothelialization of channels was noted. The lumen of laser channels were surrounded by a rim of acellular debris with several outer concentric rims of cardiomyocytes showing features of cellular destruction. The present study identified features of both necrotic and apoptotic cellular death following laser revascularization.     

Neovascularization derived from cell transplantation in ischemic myocardium

Myocardial ischemia triggers a limited angiogenic response, part of the remodeling process that is insufficient to avoid further functional impairment. Several strategies have been evaluated to regenerate myocardial vascularization after ischemic injury such as transmyocardial laser revascularization and gene therapy. Attention has recently been focused on the potential of cell therapy to induce angiogenesis. Enhancing myocardial neovascularization is a major goal of myocardial cell transplantation because it would provide patients, who cannot undergo conventional revascularization, with an alternative therapy. Additionally, neovascularization would provide the implanted cells with adequate microenvironment to enhance survival and function. This short review gives an overview of the effect of various cell transplantation strategies on myocardial neovascularization. It suggests that in order to optimize myocardial neovascularization induced by cell therapy, future experiments should focus on the contribution of exogenous and endogenous stem cells to new vessels formation, and on the identification of the molecular pathways involved in the process.     

Neovascularization derived from cell transplantation in ischemic myocardium

Myocardial ischemia triggers a limited angiogenic response, part of the remodeling process that is insufficient to avoid further functional impairment. Several strategies have been evaluated to regenerate myocardial vascularization after ischemic injury such as transmyocardial laser revascularization and gene therapy. Attention has recently been focused on the potential of cell therapy to induce angiogenesis. Enhancing myocardial neovascularization is a major goal of myocardial cell transplantation because it would provide patients, who cannot undergo conventional revascularization, with an alternative therapy. Additionally, neovascularization would provide the implanted cells with adequate microenvironment to enhance survival and function. This short review gives an overview of the effect of various cell transplantation strategies on myocardial neovascularization. It suggests that in order to optimize myocardial neovascularization induced by cell therapy, future experiments should focus on the contribution of exogenous and endogenous stem cells to new vessels formation, and on the identification of the molecular pathways involved in the process. (Mol Cell Biochem 264: 133–142, 2004)     

Intraoperative isolation and processing of BM-derived stem cells

To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in five patients undergoing coronary artery bypass grafting and transmyocardial laser revascularization. An innovative method for the intraoperative isolation of CD133(+)-stem cells in less than 3 hours has been established. After induction of general anesthesia, approx. 60-240 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device Clini-MACS. Following standard CABG surgery, LASER channels were shot in predefined areas within the hibernating myocardium. Subsequently, autologous CD133(+)-stem cells (1.9-9.7 x 10(6) cells; purity up to 97%) were injected in a predefined pattern around the laser channels. Through the intraoperative isolation of CD133(+)-cells, this effective treatment of ischemic myocardium can be applied to patients scheduled both for elective and for emergency revascularisation procedures.     

Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs

We examined the role of matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs), and plasminogen activator (PA) in transmyocardial laser revascularization (TMLR)-induced angiogenesis. TMLR was accomplished with a carbon dioxide laser in seven dogs whose left anterior descending coronary artery (LAD) was ligated. Seven control dogs underwent only LAD ligation, and four dogs underwent a sham operation, consisting only of a left thoracotomy. Two weeks later, transmural myocardial samples were harvested from the distributions of the LAD and the left circumflex artery for substrate zymography, immunohistochemical staining, and in situ zymography. MMP-1, MMP-2, TIMP-1, TIMP-2, and urokinase-type PA levels in the distribution of the LAD were higher in the laser group than in the control or sham group. Counts of von Willebrand factor-positive microvessels and smooth muscle alpha-actin-positive arterioles demonstrated that the angiogenesis and ateriogenesis was promoted in the laser group and correlated directly with the number of MMP-stained microvessels. We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR.     

同期行冠状动脉旁路移植和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床研究

目的:总结同期行冠状动脉旁路移植(CABG)和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床经验。方法:回顾性分析我院收治的41例接受冠状动脉旁路移植同期行心脏瓣膜置换术的冠心病合并心脏瓣膜病患者的临床资料,对手术方法、主要并发症和术后处理方法进行分析总结。结果:41例患者中,行二次开胸4例(9.76%),应用IABP 2例(4.88%),发生低心排综合征6例(14.63%)、肾功能不全6例(14.63%)、肺功能不全7例(17.07%)、脑合并症1例(2.44%)、胸腔积液4例(9.77%),死亡6例(13.63%),其余患者康复出院。结论:CABG同期行心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的近期疗效满意。术前改善心功能,成熟的手术技术,完全的心肌再血管化,良好的心肌保护,停机困难者尽早应用主动脉内球囊反搏(IABP)及加强术后处理是提高CABG同期行心脏瓣膜置换术疗效的重要措施。     

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.     

Morphological bases of myocardial revascularization by laser radiation

The mechanism of myocardial revascularization was studied in 30 dogs with the aid of impulse carbonic acid laser after ligation of the anterior descending branch of the left coronary artery. In the control group, 4 dogs died of myocardial infarction. In 26 animals laser canals were formed. The walls of the canals comprised cardiomyocytes with the manifestations of a coagulation thermal necrosis. Morphological studies disclosed the aseptic productive nature of the inflammatory reaction and the absence of marked leukocytic infiltration of the tissues adjacent to the area of necrosis. The laser canals were lined with endothelium by the 10th-14th day after operation, they were not obliterated or sclerosed. Morphological, laboratory, and radionuclide studies attest to adequate perfusion of the myocardium with the aid of the laser canals preventing the development of myocardial ischemia and infarction.     

T-cadherin Is Essential for Adiponectin-mediated Revascularization

Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin.     

Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival

We hypothesized that pretreatment of an infarcted heart by mechanical transmyocardial revascularization (TMR) before transplantation of bone marrow cells (BMCs) or BMC-expressing angiogenic growth factors would increase transplanted BMC survival and enhance myocardial repair. Female Lewis rats underwent coronary ligation 3 wk before creation of 10 needle TMR channels (3 groups) or no TMR (3 groups), followed by transplantation of 3 x 10(6) male donor BMCs, BMC transfected with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) (BMC + VBI), or medium alone. At 1, 3, and 7 days, we evaluated transplanted cell survival, vascular densities, and left ventricular (LV) function (N = 4 per group x 6 groups x 3 time points). At 3 days, vascular densities in the scar were increased by TMR + BMC + VBI and by BMC + VBI (P < 0.05), and at 7 days, vascular densities were greatest in rats receiving TMR + BMC + VBI (P < 0.05). Transplanted cell survival at 3 and 7 days was increased by TMR and by BMC + VBI. Combined therapy with TMR + BMC + VBI resulted in the greatest cell survival at 3 days (P < 0.05) versus BMC. After 7 days, LV ejection fraction (LVEF) was lowest in rats receiving neither BMC nor TMR and greatest in rats receiving TMR + BMC + VBI (P = 0.004). We concluded that mechanical pretreatment of infarcted myocardium by TMR enhances the effect of subsequent cell-based gene therapy on transplanted cell survival, angiogenesis, and LV function. Scar pretreatment with TMR combined with cell-based multigene therapy may maximize myocardial repair.