Laser Induced Myocardial Angiogenesis

描述(申请人提供)：越来越多的患者因终末期冠状动脉疾病而致残性心绞痛。 激光心肌血运重建术(TMR)的发展是为了提供 为这些患者提供选择。他们不服从于传统的 血运重建。在临床上，TMR成功地减轻了心绞痛症状和 改善患者的生活质量。TMR的确切机制 达到这些结果还不清楚。这项研究的目的是 探讨血管生成作为TMR发病机制的重要性。特指 以确定是否存在血管生成生长因子的上调 TMR。随着更多的内源性血管生成，新的血管应该 发育，灌注量增加，功能改善。潜在的协同效应 联合应用外源性血管生成生长因子的反应 将对TMR进行检查。由于不同的原因，反应的差异 激光的波长及其对组织穿透的差异 将会被研究。慢性心肌缺血动物模型的建立 将会被雇佣。将评估血管生成反应：1)在分子上 (1)bFGF和VEGFmRNA的表达增加； 组织学上由新血管的增加引起。血流灌注的变化将是 通过彩色微球和磁共振灌注成像进行评估。职能变化将是 由负荷超声心动图和电影MRI监测。进一步加强 心肌内加入碱性成纤维细胞生长因子可实现血管生成反应 蛋白和通过腺病毒介导的基因转移的血管内皮生长因子。终于 红外光(二氧化碳)与紫外光TMR的差异 将对光线(准分子)进行评估。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。

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.