Division of Pediatric Cardiology, Children's Hospital Los Angeles, Los Angeles, California.
Keck School of Medicine, University of Southern California, Los Angeles, California.
Am J Physiol Heart Circ Physiol. 2019 Dec 1;317(6):H1243-H1253. doi: 10.1152/ajpheart.00296.2019. Epub 2019 Oct 4.
The Fontan procedure for univentricular heart defects creates a nonphysiologic circulation where systemic venous blood drains directly into the pulmonary arteries, leading to multiorgan dysfunction secondary to chronic low-shear nonpulsatile pulmonary blood flow and central venous hypertension. Although blood viscosity increases exponentially in this low-shear environment, the role of shear-dependent ("non-Newtonian") blood viscosity in this pathophysiology is unclear. We studied three-dimensional (3D)-printed Fontan models in an in vitro flow loop with a Philips 3-T magnetic resonance imaging (MRI) scanner. A 4D flow phase-contrast sequence was used to acquire a time-varying 3D velocity field for each experimental condition. On the basis of blood viscosity of a cohort of patients who had undergone the Fontan procedure, it was decided to use 0.04% xanthan gum as a non-Newtonian blood analog; 45% glycerol was used as a Newtonian control fluid. MRI data were analyzed using GTFlow and MATLAB software. The primary outcome, power loss, was significantly higher with the Newtonian fluid [14.8 (13.3, 16.4) vs. 8.1 (6.4, 9.8)%, medians with 95% confidence interval, < 0.0001]. The Newtonian fluid also demonstrated marginally higher right pulmonary artery flow, marginally lower shear stress, and a trend toward higher caval flow mixing. Outcomes were modulated by Fontan model complexity, cardiac output, and caval flow ratio. Vortexes, helical flow, and stagnant flow were more prevalent with the non-Newtonian fluid. Our data demonstrate that shear-dependent viscosity significantly alters qualitative flow patterns, power loss, pulmonary flow distribution, shear stress, and caval flow mixing in synthetic models of the Fontan circulation. Potential clinical implications include effects on exercise capacity, ventilation-perfusion matching, risk of pulmonary arteriovenous malformations, and risk of thromboembolism. Although blood viscosity increases exponentially in low-shear environments, the role of shear-dependent ("non-Newtonian") blood viscosity in the pathophysiology of the low-shear Fontan circulation is unclear. We demonstrate that shear-dependent viscosity significantly alters qualitative flow patterns, power loss, pulmonary flow distribution, shear stress, and caval flow mixing in synthetic models of the Fontan circulation. Potential clinical implications include effects on exercise capacity, ventilation-perfusion matching, risk of pulmonary arteriovenous malformations, and risk of thromboembolism.
用于单心室心脏缺陷的 Fontan 手术会创建一种非生理循环，其中体循环静脉血液直接流入肺动脉，导致多器官功能障碍，这是由慢性低切变非脉动性肺血流和中心静脉高压引起的。尽管在这种低切变环境中血液粘度呈指数级增加，但剪切依赖性（“非牛顿”）血液粘度在这种病理生理学中的作用尚不清楚。我们使用飞利浦 3T 磁共振成像（MRI）扫描仪在体外流回路中研究了三维（3D）打印的 Fontan 模型。使用 4D 流相位对比序列获取每个实验条件的时变 3D 速度场。根据接受过 Fontan 手术的患者的血液粘度，决定使用 0.04%黄原胶作为非牛顿血液模拟物；45%甘油作为牛顿控制液。使用 GTFlow 和 MATLAB 软件分析 MRI 数据。主要结果，功率损耗，牛顿流体显著更高[14.8（13.3，16.4）比 8.1（6.4，9.8）%，中位数，95%置信区间，<0.0001]。牛顿流体还表现出稍高的右肺动脉流量、稍低的剪切应力和稍高的腔静脉流量混合趋势。结果受 Fontan 模型复杂性、心输出量和腔静脉流量比的调节。非牛顿流体中更常见的是涡流、螺旋流和停滞流。我们的数据表明，剪切依赖性粘度显著改变了合成 Fontan 循环模型中的定性流动模式、功率损耗、肺血流分布、剪切应力和腔静脉血流混合。潜在的临床意义包括对运动能力、通气-灌注匹配、肺动静脉畸形风险和血栓栓塞风险的影响。尽管在低切变环境中血液粘度呈指数级增加，但剪切依赖性（“非牛顿”）血液粘度在低切变 Fontan 循环病理生理学中的作用尚不清楚。我们证明，剪切依赖性粘度显著改变了合成 Fontan 循环模型中的定性流动模式、功率损耗、肺血流分布、剪切应力和腔静脉血流混合。潜在的临床意义包括对运动能力、通气-灌注匹配、肺动静脉畸形风险和血栓栓塞风险的影响。
