Laser Induced Myocardial Angiogenesis

激光诱导心肌血管生成

• 批准号: 6370794
• 负责人: Keith A Horvath
• 金额: $ 17.89万
• 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/6370794
• 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）：越来越多的患者因终末期冠状动脉疾病而患有致残性心绞痛。 开发经心肌激光血运重建术（TMR）是为了提供一种 这些患者的选择。不适应传统方法的人 血运重建。临床上，TMR 成功减少心绞痛症状 提高患者的生活质量。 TMR 的确切机制 取得这些成果尚不清楚。本研究的目的是 研究血管生成作为 TMR 机制的重要性。具体来说 以确定血管生成生长因子在术后是否上调 TMR。随着更多内源性血管原的产生，新血管应该 发育、灌注增加和功能改善。潜在的协同效应 对联合添加外源性血管生成生长因子的反应 与 TMR 将进行检查。由于不同的情况而导致的响应有所不同 激光的波长以及该光的组织穿透力的差异 将被研究。慢性心肌缺血动物模型的建立 将被雇用。将评估血管生成反应：1.) 通过证明 bFGF 和 VEGF mRNA 的增加为基础； 2.) 组织学上表现为新血管的增加。灌注变化将是 通过彩色微球和灌注 MRI 进行评估。功能变化将是 通过负荷超声心动图和电影 MRI 进行监测。进一步增强 血管生成反应将通过心肌内添加 bFGF 来实现 蛋白质和 VEGF 通过腺病毒介导的基因转移传递。最后 红外光（二氧化碳）与紫外光 TMR 的差异 将评估光（准分子）。虽然临床结果令人鼓舞， 更好地了解 TMR 的机制将有助于更好地治疗 这些病人。