减阻剂对冠脉再通后心肌无复流现象的影响及机制

Myocardial no-reflow phenomenon known as myocardial tissue perfusion does not occur after the occluded coronary artery have been re-opened by percutaneous coronary intervention (PCI). There are no effective methods or medicine to treat myocardial no-reflow until now. Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. A number of our early studies have found that DRPs can increase blood flow and reduce blood resistance of aorta, small arteries and capillary of rat. DRPs also can reduce myocardial infarct size in acute myocardial infarction in rats, increase survival rate and improve heart function in rats with myocardial infarction. Accordingly, we hypothesized that DRPs can reduce the resistance of coronary arteries and myocardial microcirculation, increase coronary artery blood supply, reduce myocardial no-reflow phenomenon after coronary artery recanalization. Myocardial contrast echocardiography, hemodynamic monitor, histopathology, molecular biological test and many other technologies are chose in this study. This is the first time to explore the effect and mechanism of DRPs on myocardial no-reflow phenomenon through multiple levels. DRPs may offer a new potential approach for the treatment of myocardial no-reflow phenomenon after PCI.

经皮冠脉介入治疗开通闭塞冠脉后，部分患者的缺血区心肌组织微循环血流缓慢甚至无血流灌注，这一现象被称为心肌无复流现象。目前针对心肌无复流现象的治疗尚无成熟的方法。减阻剂是一类可以降低流体阻力作用的高分子聚合物。近来我们观察到,减阻剂可以明显增加大鼠大动脉、微小动脉及毛细血管网的血流速度及减低血流阻力，也可有效地减少急性心梗大鼠的梗死面积，显著增强心功能,增加心梗后存活率。据此，我们推测：减阻剂可以通过减低冠状动脉及微循环血流阻力，增加冠脉血供，改善冠脉再通后心肌无复流现象。本研究使用心肌声学造影、血流动力学检测、组织病理学检测等不同方法，探讨急性心肌梗死后冠脉开通时减阻剂对心肌微循环的影响，并在缺血再灌注损伤、分子生物学等层面探讨其机制。首次通过整体、器官、组织形态、分子等多个层面深入探讨减阻剂对冠脉再通后心肌无复流现象的可能影响及其机制。为PCI术后心肌无复流现象的防治提供新的治疗思路。

急性心肌梗死发生后，在开通闭塞冠脉后，部分缺血区心肌组织微循环血流缓慢甚至无血流灌注，这一现象被称为心肌无复流现象。目前针对心肌无复流现象的治疗临床上尚无有效的方法。减阻剂是一类可以降低流体阻力作用的可溶性高分子聚合物。研究发现,减阻剂可以明显增加大鼠大动脉、微小动脉及局部组织毛细血管网的血流速度而减低血流阻力。本课题组通过急性心肌梗死—闭塞冠脉再通动物模型、离体心脏Langendorff再灌注模型及分子生物学检测分析，旨在探讨减阻剂改善心肌无复流现象及其可能的作用机制，指导研发新的心肌无复流保护策略。结果发现：（1）减阻剂应用后闭塞冠状动脉开通后无复流心肌的面积明显减少。（2）减阻剂对缺血再灌注损伤心肌的收缩功能及舒张功能均存在保护作用。（3）减阻剂对缺血再灌注心肌的坏死和凋亡存在一定程度的保护作用。急性心肌梗死患者在打开冠脉时，如同时使用减阻剂增加局部心肌微循环血流，可能是心肌无复流的一个潜在治疗方向。