Myocardial Cellular Stimulation of Angiogenesis

刺激心肌血管新生可能是减轻心肌缺血、改善患者生活质量的重要手段。激光血管重建术（TMR）就是这样一种方法，它使用高功率激光来产生受控的损伤并产生自然的血管生成反应。 虽然两种不同波长激光的临床结果相似，但激光组织相互作用之间存在巨大差异。 我们研究了这种差异是否会导致心肌功能的变化，以及每种激光实现临床成功的机制是否不同。 采用猪慢性心肌缺血模型，TMR后进行电影MRI、高增强MRI、静息和负荷超声心动图和组织学检查。 二氧化碳治疗后，心肌功能有显著改善，而使用钬激光YAG器械时未观察到。 治疗后6周，组织学和MRI证实Ho：YAG器械的瘢痕形成更多，血管生成更少。 在这些结果的基础上，我们开始增加细胞治疗，以进一步增强激光引起的血管生成反应。 使用已经允许分化和扩增的自体骨髓，将间充质干细胞注射到上述大型动物模型的缺血区中。 正在收集MRI、超声心动图和组织学终点，以确定是否可能有协同反应。

The stimulation of myocardial angiogenesis may be an important method to diminsh ischemia and improve the quality of patients' lives. Transmyocardial laser revascularization (TMR)is one such method that employs the use of a high powered laser to create a controlled injury and engender the natural angiogenic response. While clinical results with two different wavelengths of laser light are reportedly similar there are vast differences between the laser tissue interactions. We investigated whether this difference led to a myocardial functional change and whether the mechanisms whereby each laser achieves its clinical success is different. Employing a porcine model of chronic myocardial ischemia; cine MRI, hyperenhancement MRI, rest and stress echocardiography and histology were performed after TMR. There were significant improvements in myocardial function after treatment by a carbon dioxide that were not seen when a holmium:YAG device was used. Histology and MRI confirmed more scarrring and less angiogenesis with the Ho:YAG device at 6 weeks post treatment. Building on these results we have embarked on the addition of cellular therapy to further enhance the angiogenic response engendered by the laser. Using autologous bone marrow which has been allowed to differentiate and expand, mesenchymal stem cells are injected into the ischemic zone of the aforementioned large animal model. MRI, echo and histologic endpoints are being gathered to determine if a synergistic response is possible.