Imaging and Laser Revascularization in Hibernation

描述（由申请人提供）：鉴别慢性缺血性 功能障碍或冬眠心肌是重要的临床奋进。 不适合CABG或PICA的患者现在正在考虑 新的血运重建方法，如直接心肌血运重建 使用基于导管的方法（DMR）的激光通道。机电 内分泌（UPV）映射用于指导DMR，但尚未完全验证。 灌注成像和多巴酚丁胺超声心动图正在临床上用于 识别功能障碍存活心肌并评估新的 血管重建技术。这些成像技术的准确性， 这些适应症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力标准是不完善的。双 冬眠心肌的Ameroid缩窄肌/猪模型显示出作为 一个很好的模型来比较这些技术， 组织病理学检查，并研究DMR的疗效和机制。在 第一个目的，我们建议使用猪的广泛冬眠和疤痕模型， 验证UPV标测，以确定存活率与瘢痕，并比较铊 影像学和多巴酚丁胺超声心动图对组织病理学，以确定 活力和烧灼。在目标2和3下，双容器ameroid模型将被 用于研究DMR的机制。激光治疗的效果 将使用组合的形态测量组织分析来评估血管生成， 血管造影技术。无创显像（99 mTc-腺苷） sestamibilrest Tl-201和多巴酚丁胺超声）检测新血管形成 评估。在aim 4中，将使用放射性碘标记的MIBG放射自显影来观察 DMR对局部神经支配的影响。这些实验的结果 应更好地定义方法的准确性，以图像的可行性 和图像血管生成，并导致更好地了解DMR是否 心脏血管的重建以及心脏的神经是否被切断。

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.