Imaging and Laser Revascularization in Hibernation

描述(由申请人提供)：识别慢性缺血 心肌功能障碍或冬眠是一项重要的临床工作。 非CABG或PICA的患者现在正在考虑接受 直接心肌血运重建术等新的血管重建方法 激光通道采用基于导管的方法(DMR)。机电 心内膜(UPV)标测用于指导DMR，但尚未得到充分验证。 灌注成像和多巴酚丁胺超声心动图正被用于临床 识别功能不全的存活心肌并评估新的 血运重建技术。这些成像技术的准确性 这些迹象从未在动物模型中得到充分验证。黄金 临床研究中使用的生存能力标准并不完美。双人房 无性系缩窄器/猪冬眠心肌模型有望成为 将这些技术相互比较并与之进行比较的好模型 组织病理学检查，并探讨DMR的疗效及作用机制。在 首先，我们建议使用猪的广泛冬眠和疤痕模型。 验证UPV标测以确定生存能力与SCAR并比较铊 影像和多巴酚丁胺超声心动图对照组织病理学诊断 生存能力和灼热度。在AIMS 2和AIMS 3中，双容器非球体模型将是 用于研究DMR的机制。激光治疗青光眼的疗效观察 血管生成将使用联合形态测量组织分析和 血管造影术。无创性显像(腺苷~(99m)Tc)的疗效 静息TL-201和多巴酚丁胺超声心动图)检测新生血管 评估过了。在AIM 4中，将使用放射性碘标记的MIBG放射自显影来查看 DMR对区域神经支配的影响。这些实验的结果 应该更好地定义成像方法的准确性 和图像血管生成，并导致更好地理解DMR 使心脏血运重建，以及是否使心脏失去神经。

DESCRIPTION (Provided by Applicant): Identifying chronically ischemic dysfunctional or hibernating myocardium is an important clinical endeavor. Patients who are not candidates for CABG or PICA are now being considered for new methods of revascularization such as direct myocardial revascularization with laser channels using catheter based approach (DMR). Electromechanical endocardial (UPV) mapping is used to guide DMR but is not fully validated. Perfusion imaging and dobutamine echocardiography are being used clinically to identify dysfunctional viable myocardium and assess results of novel revascularization techniques. The accuracy of these imaging techniques for these indications have never been fully validated in an animal model. Gold standards for viability used in clinical studies are imperfect. A double ameroid constrictor/swine model for hibernating myocardium shows promise as a good model to compare these technologies against one another and against histopathology and to investigate the efficacy and mechanisms of DMR. In the first aim we propose to use swine models of extensive hibernation and of scar to validate UPV mapping to identify viability vs scar and to compare thallium imaging and dobutamine echocardiography against histopathology to identify viability and sear. Under aims 2 and 3 the double vessel ameroid model will be used to investigate mechanisms for DMR. The effect of laser therapy on angiogenesis will be assessed using combined morphometric tissue analysis and angiographic techniques. The efficacy of noninvasive imaging (adenosine Tc-99m sestamibilrest Tl-201 and dobutamine echo) to detect neovascularization will be assessed. In aim 4 radioiodinated MIBG autoradiography will be used to look at the effects of DMR on regional innervation. The results of these experiments should better define the accuracy of methods to image viability and image angiogenesis, and lead to a better understanding of whether DMR revascularizes the heart and whether or not it denervates the heart.