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）干预对大量的高风险患者（高年龄和/或患有合并症）有望，否则他们可能没有有限或没有治疗方案。尽管通过动物和人类的临床试验获得了丰富的经验，但是动物试验结果与人类试验的结果之间的差异经常存在。在该提议中，我们假设1）动物和人体瓣膜组织之间存在机械性能和解剖结构的显着差异，以及2）动物中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人类的生物力学相互作用显着不同。如果上述假设被检验为真实，则将引发有关转导阀干预动物试验有效性的问题。如果两个假设被检验为错误，则该研究可以提供解释动物和人类试验结果之间差异的见解，以促进装置开发和临床试验。在一项初步研究中，我们发现在6-9个月的猪和〜90岁的人体主动脉组织之间存在机械性能的显着差异。为了进一步测试假设1是否适用于其他年龄段的猪，绵羊和人类，在这项研究中，将研究1岁和2岁的猪的主动脉组织，6-9个月，1岁和2岁的绵羊，以及60岁和75岁的人类。为了检验两个假设，具体来说，我们提出了以下特定目的：1）研究不同年龄组的动物和人类主动脉根之间的机械性质差异； 2）研究动物和老年人主动脉根之间的解剖结构差异； 3）调查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）建立猪，卵巢和人类主动脉根的机械性能以及不同年龄段的人主动脉根的解剖结构，2）阐明动物试验在TAV干预中的作用和3）结论，在结论中具有足够的数据，可以对TAV-Aortic root antactic and thrombiolic进行R01研究。公共卫生相关：主动脉狭窄会影响许多老年人口的人，并且随着人口的老龄化，其患病率正在增加。现在正在研究经导管主动脉瓣（TAV）替代品作为替代性血管内，微创治疗方案。这项研究与对经导管主动脉瓣临床试验中动物模型的适用性研究有关。动物主动脉组织特性的年龄依赖性将被量化。当将TAV设备部署到各个年龄段的动物和人主动脉根中时，计算建模将用于阐明不同的交互式响应。