Laser Induced Myocardial Angiogenesis

激光诱导心肌血管生成

• 批准号: 6537812
• 负责人: Keith A Horvath
• 金额: $ 17.69万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537812
• 关键词: angiogenesis; disease /disorder model; echocardiography; electromagnetic radiation; fibroblast growth factor; heart revascularization; immunocytochemistry; lasers; magnetic resonance imaging; messenger RNA; microcapsule; myocardial ischemia /hypoxia; myocardium; reperfusion; swine; tissue /cell culture; transfection /expression vector; vascular endothelial growth factors

DESCRIPTION (Provided by Applicant): There are an increasing number of patients with disabling angina as a result ot end-stage coronary artery disease. Transmyocardial laser revascularization (TMR) was developed to provide an option for these patients. who are not amenable to conventional methods of revascularization. Clinically, TMR successfully reduces anginal symptoms and improves the quality of the patient's life. The exact mechanism whereby TMR achieves these results is unclear. The objective of this study is to investigate the importance of angiogenesis as a mechanism of TMR. Specifically to determine if there is an upregulation of angiogenic growth factors after TMR. With more endogenous production of angiogens, new blood vessels should develop, perfusion increase and function improve. The potential synergistic response to the addition of exogenous angiogenic growth factors in combination with TMR will be examined. Variations in the response due to different wavelengths of laser light and differences in tissue penetration of this light will be studied. An established animal model of chronic myocardial ischemia will be employed. The angiogenic response will be assessed: 1.) on a molecular basis by demonstrating an increase in the mRNA for bFGF and VEGF; 2.) histologically by an increase in new blood vessels. Perfusion changes will be assessed by colored microspheres and perfusion MRI. Functional changes will be monitored by stress echocardiography and cine MRI. Further enhancement of the angiogenic response will be achieved by the intramyocardial addition of bFGF protein and by VEGF delivered via an adenoviral mediated gene transfer. Finally the differences in TMR by infrared light (carbon dioxide) versus ultraviolet light (excimer) will be assessed. While the clinical results are encouraging, better understanding of the mechanisms of TMR will lead to better treatment for these patients.

描述（由申请人提供）：由于终末期冠状动脉疾病，致残心绞痛的患者数量越来越多。 开发了跨膜激光血运重建（TMR）以提供 这些患者的选择。谁不适合传统方法 血运重建。在临床上，TMR成功减少了角质症状和 改善患者生活的质量。 TMR的确切机制 实现这些结果尚不清楚。这项研究的目的是 研究血管生成作为TMR机制的重要性。具体来说 确定在 TMR。随着血管生成更多的内源性产生，新的血管应 发展，灌注增加并改善功能。潜在的协同作用 对组合中外源性血管生长因子的添加的响应 将检查TMR。由于不同的响应变化 激光光的波长和该光的组织穿透的差异 将被研究。慢性心肌缺血的既定动物模型 将被雇用。将评估血管生成反应：1。）在分子上 通过证明BFGF和VEGF的mRNA增加的基础； 2.） 在组织学上，新血管的增加。灌注变化将是 通过有色微球和灌注MRI评估。功能更改将是 通过应力超声心动图和Cine MRI监测。进一步增强 血管生成反应将通过心脏内添加BFGF来实现 蛋白质和通过腺病毒介导的基因转移传递的VEGF。最后 红外光（二氧化碳）与紫外线的TMR差异 光（准分子）将进行评估。虽然临床结果令人鼓舞，但 更好地了解TMR机制将为您提供更好的治疗 这些患者。