经导管植入"瓣上瓣"对急性主动脉瓣返流动物冠脉血流储备和心肌灌注的影响机制研究

Falling from a height or being involved in a car accident can often lead to cardiac vessels damage, especially aortic valve injury leading to acute aortic regurgitation. In many patients, particularly those with more severe trauma, emergency surgical valve repair can not be done. Currently, transcatheter aortic valve implantation (TAVI) has become a hot field of interventional cardiology. However, the TAVI technology has been mostly applied in high-risk patients with symptomatic severe aortic stenosis. This technology is not recommended in patients with aortic regurgitation. Our preliminary study has suggested that transcatheter valve implantation above the coronary ostia (valve-up-valve) in animals with acute aortic regurgitation, animals still can survive. These results indicated that the "valve-up-valve" can reduce the aortic regurgitation. This novel intervention may be an effective bridge between medicine and surgery. Therefore, based on the previous results, this project intends to investigate the effect and mechanism of transcastheter "valve-up-valve" implantation on coronary artery flow reserve and myocardial perfusion in animals with acute aortic valve regurgitation. According to these preliminary studies, we expect to establish a minimally invasive method of treatment of aortic regurgitation and provide experimental basis.

高空坠落或交通事故等创伤可引起急性主动脉瓣返流，这类患者多合并严重外伤，不适合行急诊外科瓣膜修复术。目前，经导管主动脉瓣植入术已成为瓣膜病介入治疗的热点话题，但该技术主要用于高危的重度主动脉瓣狭窄患者，对于主动脉瓣返流，尚不推荐在原位植入瓣膜支架。申请人前期研究发现，经导管在急性主动脉瓣返流动物的冠脉开口上缘植入人工瓣膜（"瓣上瓣"）后，主动脉瓣返流减轻，动物可存活，这提示"瓣上瓣"的植入有可能在患者过渡至外科手术前起到"桥梁"作用，但前期研究尚未对"瓣上瓣"术后的心肌供血进行定量评估。本课题拟在此基础上，对急性主动脉瓣返流动物"瓣上瓣"植入后的心肌供血状态进一步研究。在建立不同返流程度的急性主动脉瓣返流模型后，经导管在模型动物的冠脉开口上缘植入瓣膜支架，采用影像学和分子生物学技术研究"瓣上瓣"植入后冠脉血流及心肌灌注的近远期变化，从而为建立一种介入治疗急性主动脉瓣返流的方法提供实验依据。

高空坠落或交通事故等创伤可引起急性主动脉瓣返流，这类患者多合并严重外伤，不适合行急诊外科瓣膜修复术。目前，经导管主动脉瓣植入术已成为瓣膜病介入治疗的热点话题，但该技术主要用于高危的重度主动脉瓣狭窄患者，因此对于主动脉瓣返流，尚不推荐在原位植入瓣膜支架。本课题拟研究一种微创的方法，减轻急性主动脉瓣反流的反流量，为后期矫正治疗赢得时间。我们首先采用经导管穿刺瓣叶的方法建立了实验犬急性主动脉瓣反流的动物模型，然后用自行研制的自膨胀瓣膜支架采用经导管植入的方法在急性主动脉瓣返流动物的冠脉开口上缘植入人工瓣膜（即"瓣上瓣"植入），术后三个月的临床随访结果证实，实验动物并未因急性主动脉瓣反流造成的心力衰竭而致死，反而可短期存活，且我们采用超声心动图和血流动力学监测等手段进行评估后发现，这种方法并未影响到实验动物的冠脉血流灌注和心肌供血，随访期间实验动物的心功能未见明显减退。故本课题的研究结果初步证实，这种经导管“瓣上瓣”植入的方法可明显减轻因创伤引起的急性主动脉瓣反流的反流量，为后期临床上建立一种介入治疗急性主动脉瓣返流的方法提供了实验依据。