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: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7735008
• 关键词: Aftercare; Animal Model; Autologous; Blood Vessels; Bone Marrow; Carbon Dioxide; Chronic; Cine Magnetic Resonance Imaging; Clinical; Devices; End Point; Family suidae; Growth; Heart; Histologic; Histology; Holmium; Injury; Ischemia; Lasers; Life; Light; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methods; Modeling; Myocardial; Myocardial Ischemia; Patients; Rest; Stress Echocardiography; Tissues; Week; angiogenesis; improved; interest; paracrine; response; success

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.

刺激心肌血管生成可能是减少缺血、提高患者生活质量的重要方法。经心肌激光血运重建（TMR）就是一种这样的方法，它利用高功率激光来产生受控损伤并产生自然的血管生成反应。 据报道，虽然两种不同波长激光的临床结果相似，但激光组织相互作用之间存在巨大差异。 我们研究了这种差异是否导致心肌功能改变，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； TMR 后进行电影 MRI、超增强 MRI、休息和负荷超声心动图以及组织学检查。 经过二氧化碳治疗后，心肌功能得到显着改善，而使用钬：YAG 装置时未见这种情况。 组织学和 MRI 证实 Ho:YAG 装置在治疗后 6 周后疤痕增多，血管生成减少。 基于这些结果，我们开始添加细胞疗法，以进一步增强激光产生的血管生成反应。 使用已经分化和扩增的自体骨髓，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、回波和组织学终点以确定是否可能产生协同反应。

项目成果

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
• 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
• 作者: Horvath,KeithA;FergusonJr,TBruce;Guyton,RobertA;Edwards,FredH
• 通讯作者: Edwards,FredH

Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension.

• 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
• 作者: Horvath,KeithA;Berry,GeraldJ;ICEMInvestigators
• 通讯作者: ICEMInvestigators

Topical application of bacitracin ointment is associated with decreased risk of mediastinitis after median sternotomy.

局部应用杆菌肽软膏可降低正中胸骨切开术后纵隔炎的风险。

• DOI: 10.1532/hsf98.20051187
• 发表时间: 2006
• 期刊: The heart surgery forum
• 作者: MacIver,RobroyH;Stewart,Robert;Frederiksen,JamesW;Fullerton,DavidA;Horvath,KeithA
• 通讯作者: Horvath,KeithA