Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition.
Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition.
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DOI：
10.3389/fbioe.2021.779043
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发表时间：
2021
影响因子：
5.7
通讯作者：
Shiu YT
中科院分区：
文献类型：
--
作者：
Northrup H;Somarathna M;Corless S;Falzon I;Totenhagen J;Lee T;Shiu YT
动静脉内瘘（AVF）对于接受血液透析的慢性肾病（CKD）患者至关重要，但 AVF 成熟失败的治疗仍然是一个未得到满足的临床需求。成功的 AVF 重塑是通过充分的管腔扩张来增加 AVF 血流量和管腔面积而实现的。异常血流被认为会损害 AVF 重塑，但之前的文献主要集中于整个 AVF 或单个位置的平均血流动力学。我们假设血流动力学是异质的，因此任何治疗在 AVF 中的效果大小都是异质的。为了检验我们的假设，我们使用 PDE5A 抑制剂西地那非治疗大鼠模型中的 AVF，并进行基于计算流体动力学 (CFD) 的磁共振成像 (MRI)，以生成 AVF 血流动力学的详细空间概况。将 90 毫克/千克的西地那非加入大鼠的饮用水中给药，持续 14 天。第 14 天，在大鼠中制作股骨 AVF，并继续西地那非治疗 21 天。 AVF 创建后 21 天，大鼠接受非对比 MRI 进行 CFD 和几何分析。管腔横截面积 (CSA) 和流速用于量化 AVF 重塑。用于描述异常血流的参数包括速度大小、壁剪切应力 (WSS)、振荡剪切指数 (OSI) 和涡度。几何参数包括动静脉 (A-V) 距离、吻合角度、弯曲度和非平面角度大小。当对整个 AVF 进行平均时，西地那非治疗的大鼠的 CSA、流速、速度、WSS、OSI 和涡度显着高于对照大鼠。为了分析异质性，将静脉分为距离吻合处 0-5、5-10、10-15 和 15-20 毫米的区域。在两组中：1) CSA 从 0-5 区域增加到 15-20 区域； 2）速度、WSS和涡度在0-5区域最高，此后显着下降； 3）OSI在5-10区域增加，然后逐渐减少。因此，西地那非对 AVF 重塑的影响大小以及血流动力学与 AVF 重塑之间的关系取决于位置。对照组和西地那非组之间的其他几何参数没有显着差异。大鼠对西地那非治疗的耐受性良好，我们的结果表明西地那非可能是 AVF 成熟的安全有效的治疗方法。
Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. Aberrant blood flow is thought to impair AVF remodeling, but previous literature has largely focused on hemodynamics averaged over the entire AVF or at a single location. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. To test our hypothesis, we used the PDE5A inhibitor sildenafil to treat AVFs in a rat model and performed magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) to generate a detailed spatial profile of hemodynamics in AVFs. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. In both groups: 1) CSA increased from the 0–5 to 15–20 zone; 2) velocity, WSS, and vorticity were highest in the 0–5 zone and dropped significantly thereafter; and 3) OSI increased at the 5–10 zone and then decreased gradually. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. There was no significant difference between control and sildenafil groups for the other geometric parameters. Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation.