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In vitro multi scale models to study the early stage circulations for single ventricle heart diseases palliations.

机译：体外多尺度模型用于研究单室性心脏病姑息的早期循环。

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摘要

Single ventricle physiology can result from various congenital heart defects in which the patient has only one functional ventricle. Hypoplastic left heart syndrome refers to patients born with an underdeveloped left ventricle. A three stage palliation strategy is applied over the first several years of life to establish a viable circulation path using the one functioning ventricle. Results of the first stage Norwood procedure on neonates with hypoplastic left heart syndrome are unsatisfactory with high morbidities and mortalities primarily due to high ventricle load and other complications. An early second stage Bidirectional Glenn (BDG) procedure is not a suitable option for neonates due to their high pulmonary vascular resistance (PVR), which limits pulmonary blood flow. Realistic experimental models of these circulations are not well established and would be useful for studying the physiological response to surgical decisions on the distribution of flows to the various territories, so as to predict clinical hemodynamics and guide clinical planning. These would serve well to study novel intervention strategies and the effects of known complications at the local and systems-level. This study proved the hypothesis that it is possible to model accurately the first and second stage palliation circulations using multi-scale in vitro circulation models and to use these models to test novel surgical strategies while including the effects of possible complications.;A multi-scale mock circulatory system (MCS), which couples a lumped parameter network model (LPN) of the neonatal circulation with an anatomically accurate three-dimensional model of the surgical anastomosis site, was built to simulate the hemodynamic performance of both the Stage 1 and Stage 2 circulations. A pediatric ventricular assist device was used as the single ventricle and a respiration model was applied to the Stage 2 circulation system. Resulting parameters measured were pressure and flow rates within the various territories, and systemic oxygen delivery (OD) were calculated.;The Stage 1 and Stage 2 systems were validated by direct comparisons of time-based and mean pressures and flow rates between the experimental measurements, available clinical recordings and/or CFD simulations. Regression and correlation analyses and unpaired t-tests showed that there was excellent agreement between the clinical and experimental time-based results as measured throughout the circulations (0.60 < R2 0.05, sigma < 5%).;A novel, potentially alternative surgical strategy for the initial palliation, was proposed and was tested, called the assisted bidirectional Glenn (ABG) procedure. The approach taps the higher potential energy of the systemic circulation through a systemic to caval shunt with nozzle to increase pulmonary blood flow and oxygen delivery within a superior cavopulmonary connection. Experimental model was validated against a numerical model (0.65 < R 2 0.05). The tested results demonstrated the ABG had two main advantages over the Norwood circulation. First, the flow through the ABG shunt is a fraction of the pulmonary flow, reducing the volume overload on the single ventricle and improving systemic and coronary perfusion. Second, the ABG should provide a more stable source of pulmonary flow, which should reduce thrombotic risk or intimal thickening over an mBT shunt.;A study to examine the ejector pump effect was conducted. Two parameters were investigated: (1) the superior vena cava (SVC) and pulmonary artery (PA) pressure difference; and (2) the SVC and PA pressure difference relative to PA flow rate. Results validated the hypothesis that an ejector pump advantage can be adopted in a superior cavo-pulmonary circulation, where the low-energy pulmonary blood flow can be assisted by an additional source of high energy flow from the systemic circulation. But the ejector pump effect produced by the current nozzle designs was not strong.;Parametric study includes nozzle size, placement, and nozzle shape was conducted. Results shown that nozzle to shunt diameter ratio had the most important effects on the ABG performance. As beta increased, pulmonary artery flow rate and systemic oxygen delivery increased. A suggested beta value falls between 0.48 and 0.72. The study showed that a bigger beta produced a smaller resistance value. The shape of the nozzle did not change the resistance value. The effects of shunt angle, nozzle placement and nozzle shape on the ABG circulation were not statistical significant.;The aortic coarctation study showed that the aortic coarctation could have an effect on the ABG circulation. The coarctation index (CoI) around 0.5 was found to be the transition point between no effects (CoI > 0.5) and discernible effects on the ABG circulation. These effects include changes in pulmonary to systemic flow distribution.;In summary, this research verified and validated an in vitro mock circulatory system (MCS) for Stage 1 and Stage 2 circulations. The system was used to assess a novel conceptual surgery option named the ABG. Parametric studies were conducted to give guidance on designing the important element for the ABG: the shunt (nozzle) connecting the SVC and systemic circulation. The performance of the ABG under one unhealthy condition, namely, aortic coarctation was assessed.
机译：单心室生理可以由多种先天性心脏缺陷导致，其中患者只有一个功能性心室。发育不良的左心综合征是指出生时左心室发育不全的患者。在生命的最初几年中采用了三阶段缓解策略，以使用一个起作用的心室建立可行的循环路径。患有左心发育不全综合征的新生儿进行的第一阶段Norwood手术的结果并不令人满意，其发病率和死亡率很高，这主要是由于心室负荷高和其他并发症引起的。早期的第二阶段双向Glenn（BDG）手术由于其高的肺血管阻力（PVR）而限制了肺血流，因此不适用于新生儿。这些循环的现实实验模型还没有很好地建立，将有助于研究对手术决策的生理反应，以决定流向各个地区的流量，从而预测临床血液动力学并指导临床计划。这些将很好地研究新的干预策略以及已知的并发症在局部和系统级的影响。这项研究证明了这样的假设，即可以使用多尺度体外循环模型准确地对第一和第二阶段的姑息循环进行建模，并使用这些模型来测试新颖的手术策略，同时包括可能的并发症的影响。模拟循环系统（MCS）将新生儿循环的集总参数网络模型（LPN）与手术吻合部位的解剖学精确的三维模型相结合，以模拟第1阶段和第2阶段的血液动力学性能流通。儿科心室辅助设备用作单心室，呼吸模型应用于第二阶段循环系统。测得的最终参数是各个区域内的压力和流速，并计算了系统氧气输送量（OD）。第1阶段和第2阶段系统通过在实验测量之间对时基压力，平均压力和流速进行直接比较而得到验证，可用的临床记录和/或CFD模拟。回归和相关性分析以及未配对的t检验显示，在整个循环中测量的临床和实验基于时间的结果之间有很好的一致性（0.60 0.5）和对ABG循环有明显影响之间的过渡点。这些影响包括肺向全身血流分布的变化。，这项研究验证并验证了用于第1阶段和第2阶段循环的体外模拟循环系统（MCS）。该系统用于评估名为ABG的新型概念性手术方案。进行了参数研究，为设计ABG的重要要素提供了指导：连接SVC和全身循环的分流器（喷嘴）。在一种不健康的情况下，即主动脉缩窄，评估了ABG的性能。

著录项

  • 作者

    Zhou, Jian.;

  • 作者单位

    Clemson University.;

  • 授予单位 Clemson University.;
  • 学科 Biomedical engineering.;Surgery.;Mechanical engineering.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 163 p.
  • 总页数 163
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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