1 ViVitro Systems Inc. (VSI), Victoria, BC, Canada ; 2 Lake Oswego, OR, USA.
Ann Transl Med. 2015 Aug;3(14):197. doi: 10.3978/j.issn.2305-5839.2015.08.18.
Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence.
Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves.
Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0).
Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach.
探索人工心脏瓣膜血栓形成的原因时，通常集中在瓣叶关闭前后的血流细节上。在之前的实验室研究中，我们发现瓣叶关闭时会产生高振幅、短持续时间的血流速度，这意味着在瓣叶关闭时可能会产生较大的剪切力，从而启动血液凝固途径。这可能与机械瓣和生物瓣血栓形成的广泛公认的临床差异有关。我们设计了一系列原型双叶瓣机械瓣，并尝试降低瓣叶关闭时的相关血流速度，目标是确定一种具有与我们的生物瓣对照相似血栓形成潜力的原型瓣。这种迭代设计方法可能适用于评估抗栓治疗的机械瓣的临床前评估。
测试的瓣膜包括：原型机械双叶瓣（n=56）、对照瓣膜（n=2）和其他研究者的早期专利原型机械瓣（n=2）。使用脉动和准稳态流系统进行测试。使用先前描述的新型技术测量预测动态瓣口面积（PDVA）。通过体积流量/PDVA 确定瓣叶开启和关闭期间的血流速度。对于关闭瓣叶期间，使用准稳态背压/流量测试获得的数据。使用相对生物瓣和机械瓣对照的血栓形成潜力指数（TPI）对性能进行排序。
原型瓣膜设计的优化导致了 3D 打印模型（BV3D）的产生。对于二尖瓣/主动脉瓣位置，BV3D 的 TPI（1.10/1.47）低于对照机械瓣（3.44/3.93），与对照生物瓣（理想 TPI≤1.0）相似。
使用独特的技术、快速原型设计和血栓形成潜力评分，加快和简化了降低实验性瓣膜血栓形成潜力的优化过程。确定了一些创新的机械瓣膜结构，值得进一步开发，这可能使抗栓治疗的机械瓣成为可能。
