以鱼鳔为瓣膜材料的新型经导管人工心脏瓣膜的实验研究

After 21century, transcatheter heart valve implantation has rapidly developed. However, the available transcatheter heart valve material is restricted to bovine pericardium. No matter bovine pericardium or porcine valve used as bioprosthesis valve material，early failure is their common defect. Furthermore it is found that bovine pericardium is easy to calcifacate and fail because of fiber damage during the folding process. It is reported swim bladder can be used to repair animal organ, and is not apt to calcificate, but no one has systematically tested swim bladder as cardiovascular material. We have found in previous study, structure of swim bladder is similar to human heart valve, the physical properties and biocompatibility is much better than bovine pericardium. In-vivo rat trials including subcutaneous implantation and small cliber vessel transplantation which swim bladder showed great superiority than bovine pericardium. In this project, we are aim to evaluate valvular functionality after transcatheter pulmonary valve replacement in sheep using a novel swim bladder pulmonary valve and to provide the basis for clinical application.

进入21世纪以来，经导管心脏介入瓣膜置入技术飞速发展。然而目前介入瓣膜材料只有牛心包，不论是以牛心包或者猪瓣膜作为生物瓣膜材料，都存在早期衰败的缺陷。实验发现，作为支架瓣膜时，牛心包经过压缩折叠后出现组织撕裂，会加速瓣膜钙化、衰败过程。曾有报道应用鱼鳔修补动物器官，效果满意，并且不易钙化，但从未见将其应用于心血管材料并系统检测。我们在前期研究中以牛心包为对照，对鱼鳔进行系统的监测，结果表明鱼鳔结构接近人瓣膜，力学性质、生物相容性优于牛心包。进一步行体内钙化动物实验及作为血管材料行大鼠腹主动脉原位移植试验，结果表明，鱼鳔体内钙化程度以及血管远期通畅率显著优于牛心包。本课题拟在此基础上，以鱼鳔为生物材料制作成球囊扩张型介入肺动脉瓣，进行绵羊体内原位置入，对其可行性、安全性、耐久性以及中长期衰败进行全面评估，为下一步临床应用提供基础。

目前经导管介入瓣已经成功应用于临床，然而目前介入瓣膜材料局限于牛心包及猪主动脉瓣，且都存在瓣膜早期衰败的风险。最近研究表明，应用鱼鳔修补动物器官效果满意且不易钙化。鱼鳔材料应于心血管领域目前未见报道。我们在前期研究中以牛心包作为阳性对照材料，对鱼鳔进行系统的材料学评估。结果表明鱼鳔显微结构接近人瓣膜，力学性质、生物相容性明显优于牛心包。进一步把鱼鳔作为血管补片材料，行大鼠腹主动脉原位移植试验。动物实验结果表明，鱼鳔血管远期通畅率显著优于牛心包，且钙化程度较低。本项目在前期基础上，通过设计并成功制作以鱼鳔膜为生物材料的介入肺动脉瓣;并完成了体外流体力学试验及疲劳试验，初步明确了缝合的鱼鳔膜介入肺动脉瓣结构稳定性及耐用性；通过将鱼鳔膜介入肺动脉瓣原位植入绵羊肺动脉瓣处并长期随访，评估鱼鳔膜介入肺动脉瓣植入体内的可行性、安全性、耐久性。本研究旨在对比鱼鳔与牛心包介入瓣膜，评估鱼鳔与牛心包作为生物材料性能优劣，为鱼鳔下一步临床应用提供基础。