Hu Zinan, Herrmann Jessica E, Schwarz Erica L, Gerosa Fannie M, Emuna Nir, Humphrey Jay D, Feinberg Adam W, Hsia Tain-Yen, Skylar-Scott Mark A, Marsden Alison L
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
School of Medicine, Stanford University, Stanford, CA 94305.
J Biomech Eng. 2025 Jul 1;147(7). doi: 10.1115/1.4068319.
For single ventricle congenital heart patients, Fontan surgery is the final stage in a series of palliative procedures, bypassing the heart to enable passive flow of de-oxygenated blood from the inferior vena cava (IVC) to the pulmonary arteries. This circulation leads to severely elevated central venous pressure, diminished cardiac output, and thus numerous sequelae and premature mortality. To address these issues, we propose a bioprinted pulsatile conduit to provide a secondary power source for the Fontan circulation. A multiphysics computational framework was developed to predict conduit performance and to guide design prior to printing. Physics components included electrophysiology, cardiomyocyte contractility, and fluid-structure interaction coupled to a closed-loop lumped parameter network representing Fontan physiology. A range of myocardial contractility was considered and simulated. The initial conduit design with adult ventricular cardiomyocyte contractility values coupled to a Purkinje network demonstrated potential to reduce liver (IVC) pressure from 16.4 to 9.3 mmHg and increase cardiac output by 29%. After systematically assessing the impacts of contraction duration, fiber direction, and valve placement on conduit performance, we identified a favorable design that successfully reduces liver pressure to 7.3 mmHg and increases cardiac output by 38%, almost normalizing adverse hemodynamics in the lower venous circulation. Valves at the input and output of the conduit are essential to achieve these satisfactory results; without valves, performance is compromised. However, a potential drawback of the design is the elevation of superior vena cava (SVC) pressure, which varies linearly with liver pressure reduction.
对于单心室先天性心脏病患者，Fontan手术是一系列姑息性手术的最后阶段，该手术绕过心脏，使来自下腔静脉（IVC）的脱氧血液能够被动流入肺动脉。这种循环会导致中心静脉压严重升高、心输出量减少，进而引发众多后遗症和过早死亡。为了解决这些问题，我们提出了一种生物打印的搏动性管道，为Fontan循环提供辅助动力源。我们开发了一个多物理场计算框架，用于预测管道性能并在打印前指导设计。物理组件包括电生理学、心肌细胞收缩性以及与代表Fontan生理学的闭环集总参数网络耦合的流固相互作用。我们考虑并模拟了一系列心肌收缩性。最初的管道设计将成人心室心肌细胞收缩性值与浦肯野网络耦合，显示出将肝脏（IVC）压力从16.4 mmHg降至9.3 mmHg并使心输出量增加29%的潜力。在系统评估收缩持续时间、纤维方向和瓣膜位置对管道性能的影响后，我们确定了一种有利的设计，该设计成功地将肝脏压力降至7.3 mmHg，并使心输出量增加38%，几乎使下腔静脉循环中的不良血流动力学恢复正常。管道输入和输出端的瓣膜对于取得这些满意结果至关重要；没有瓣膜，性能就会受到影响。然而，该设计的一个潜在缺点是上腔静脉（SVC）压力升高，它随肝脏压力降低呈线性变化。
