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Myocardial Cellular Stimulation of Angiogenesis

Myocardial Cellular Stimulation of Angiogenesis
血管生成的心肌细胞刺激
批准号:
7735008
负责人:
Keith A Horvath
金额:
$36.6万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至

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中文摘要
翻译
促进心肌血管生成可能是减轻心肌缺血、提高患者生活质量的重要手段。激光心肌血运重建术(TMR)是一种利用高功率激光造成受控损伤并产生自然血管生成反应的方法。虽然据报道,两种不同波长的激光的临床结果相似,但激光与组织的相互作用之间存在巨大差异。我们调查了这种差异是否导致了心肌功能的改变,以及每种激光取得临床成功的机制是否不同。 采用猪慢性心肌缺血模型,在TMR后进行电影MRI、高增强MRI、静息和负荷超声心动图及组织学检查。在二氧化碳治疗后,心肌功能有了显著的改善,这在使用Ho:YAG装置时是看不到的。组织学和MRI证实,在治疗后6周,Ho:YAG装置有更多的瘢痕形成和更少的血管生成。 在这些结果的基础上,我们开始了细胞疗法的补充,以进一步增强激光产生的血管生成反应。利用已被允许分化和扩张的自体骨髓,将间充质干细胞注射到上述大型动物模型的缺血区。正在收集MRI、ECHO和组织学终点,以确定是否有可能产生协同反应。
英文摘要
The stimulation of myocardial angiogenesis may be an important method to diminsh ischemia and improve the quality of patients' lives. Transmyocardial laser revascularization (TMR)is one such method that employs the use of a high powered laser to create a controlled injury and engender the natural angiogenic response. While clinical results with two different wavelengths of laser light are reportedly similar there are vast differences between the laser tissue interactions. We investigated whether this difference led to a myocardial functional change and whether the mechanisms whereby each laser achieves its clinical success is different. Employing a porcine model of chronic myocardial ischemia; cine MRI, hyperenhancement MRI, rest and stress echocardiography and histology were performed after TMR. There were significant improvements in myocardial function after treatment by a carbon dioxide that were not seen when a holmium:YAG device was used. Histology and MRI confirmed more scarrring and less angiogenesis with the Ho:YAG device at 6 weeks post treatment. Building on these results we have embarked on the addition of cellular therapy to further enhance the angiogenic response engendered by the laser. Using autologous bone marrow which has been allowed to differentiate and expand, mesenchymal stem cells are injected into the ischemic zone of the aforementioned large animal model. MRI, echo and histologic endpoints are being gathered to determine if a synergistic response is possible.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach.
使用联合经心肌血运重建和基因治疗方法改善慢性缺血猪模型的心肌收缩力。
DOI: 10.1016/j.jtcvs.2004.10.017
发表时间: 2005
期刊: The Journal of thoracic and cardiovascular surgery
影响因子: --
作者: [Horvath,KeithA, Lu,ChiaYangJ, Robert,Emmanuel, Pierce,GlennF, Greene,Rodney, Sosnowski,BarbaraA, Doukas,John]
通讯作者: Doukas,John
Impact of unstable angina on outcomes of transmyocardial laser revascularization combined with coronary artery bypass grafting.
不稳定心绞痛对心肌激光血运重建联合冠状动脉旁路移植术结局的影响。
DOI: 10.1016/j.athoracsur.2005.06.020
发表时间: 2005
期刊: The Annals of thoracic surgery
影响因子: --
作者: [Horvath,KeithA, FergusonJr,TBruce, Guyton,RobertA, Edwards,FredH]
通讯作者: Edwards,FredH
DOI: 10.1161/01.res.0000258855.60637.58
发表时间: 2007-03-02
期刊: Circulation research
影响因子: 20.1
作者: [Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ]
通讯作者: Clark AJ
The incidence of emboli during cardiac surgery: a histopathologic analysis of 2297 patients.
心脏手术期间栓塞的发生率:2297 名患者的组织病理学分析。
DOI: 10.1532/hsf98.20041176
发表时间: 2005
期刊: The heart surgery forum
影响因子: --
作者: [Horvath,KeithA, Berry,GeraldJ, ICEMInvestigators]
通讯作者: ICEMInvestigators
Laser Induced Myocardial Angiogenesis
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