Role of Animal Models in Transcatheter Valve Intervention

动物模型在经导管瓣膜介入治疗中的作用

基本信息

批准号：
8264590
负责人：
Wei Sun
金额：
$ 22.59万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-15 至 2014-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Minimally invasive transcatheter aortic valve (TAV) intervention holds promise for a large number of high- risk patients (advanced age and/or with co-morbidities) who might otherwise have limited or no treatment options. Although significant experience has been gained through animal and human clinical trials, disparity between the results of animal trials and those of human trials often exists. In this proposal, we hypothesize that 1) significant differences in the mechanical properties and the anatomic structure exist between animal and human valve tissues, and 2) the biomechanical interaction between a TAV implant and the hosting aortic tissue is significantly different in an animal than in a human. If the above hypotheses are tested to be true, it will raise questions on the validity of animal trials in transcatheter valve intervention. If either of the hypotheses is tested to be false, the study can provide insight on interpreting differences between animal and human trial results to facilitate device development and clinical trials. In a preliminary study, we have found that significant differences in mechanical properties exist between 6-9 months porcine and ~90 year old human aortic tissues. To further test if the hypothesis 1 is valid for other age groups of pig, sheep and human, in this study, aortic tissues of 1- and 2-year old pigs, 6-9 months, 1- and 2-year old sheep, and 60- and 75-year old humans will be studied. To test both of hypotheses, specifically, we propose the following specific aims: 1) Investigation of mechanical property difference between animal and aged human aortic roots at different age groups; 2) Investigation of anatomic structural difference between animal and aged human aortic roots; 3) Investigation of responses of TAV deployment into animal and aged human aortic roots. Project milestones are to: 1) establish databases (knowledge-bases) of mechanical properties and anatomic structures of porcine, ovine and human aortic roots from different age groups, 2) clarify the role of animal trials in TAV intervention and 3) at the conclusion, have sufficient data to warrant a R01 study of TAV-aortic root interaction with thromboembolic and flow dynamic effects. PUBLIC HEALTH RELEVANC: Aortic stenosis affects many individuals of the elderly population, and its prevalence is increasing with an aging population. Transcatheter aortic valve (TAV) replacement is now being investigated as an alternative endovascular, minimally invasive treatment option. This study is related to the investigation of applicability of animal (porcine and ovine) models in transcatheter aortic valve clinical trials. Age-dependency of animal aortic tissue properties will be quantified. Computational modeling will be utilized to elucidate different interactive responses when a TAV device is deployed into animal and human aortic roots of various age groups.

描述（由申请人提供）：微创经导管主动脉瓣 (TAV) 干预为大量高危患者（高龄和/或患有合并症）带来了希望，否则他们的治疗选择可能有限或没有。尽管通过动物和人体临床试验获得了重要的经验，但动物试验的结果与人体试验的结果之间经常存在差异。在本提案中，我们假设 1) 动物和人类瓣膜组织之间存在机械性能和解剖结构的显着差异，2) TAV 植入物与宿主主动脉组织之间的生物力学相互作用在动物中与在动物中显着不同一个人。如果上述假设被检验为真，将会引发对经导管瓣膜介入动物试验有效性的质疑。如果其中任何一个假设被测试为错误，该研究可以提供解释动物和人体试验结果之间差异的见解，以促进设备开发和临床试验。在一项初步研究中，我们发现 6-9 个月大的猪和约 90 岁的人类主动脉组织在机械性能上存在显着差异。为了进一步检验假设1对于其他年龄组的猪、羊和人是否成立，本研究采用1岁和2岁猪、6-9个月、1岁和2岁羊的主动脉组织，还将对 60 岁和 75 岁的人类进行研究。为了检验这两个假设，具体而言，我们提出以下具体目标：1）研究不同年龄组动物和老年人主动脉根部的力学性能差异； 2）研究动物和老年人主动脉根部的解剖结构差异； 3) 研究 TAV 部署到动物和老年人主动脉根部的反应。项目里程碑是：1) 建立不同年龄组的猪、羊和人类主动脉根部的机械特性和解剖结构数据库（知识库），2) 阐明动物试验在 TAV 干预中的作用，3) 结论，有足够的数据来保证 TAV-主动脉根部与血栓栓塞和血流动力学效应相互作用的 R01 研究。公共卫生相关性：主动脉瓣狭窄影响许多老年人群，并且其患病率随着人口老龄化而增加。经导管主动脉瓣 (TAV) 置换术目前正在研究作为一种替代性血管内微创治疗选择。本研究与动物（猪和羊）模型在经导管主动脉瓣临床试验中的适用性调查相关。动物主动脉组织特性的年龄依赖性将被量化。当 TAV 装置部署到不同年龄组的动物和人类主动脉根部时，计算模型将用于阐明不同的交互反应。