Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension.
Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension.
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DOI：
10.1186/s12968-021-00759-8
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发表时间：
2021-06-03
期刊：
影响因子：
--
通讯作者：
Kheyfets VO
中科院分区：
文献类型：
--
作者：
Dufva MJ;Boehm M;Ichimura K;Truong U;Qin X;Tabakh J;Hunter KS;Ivy D;Spiekerkoetter E;Kheyfets VO
心室力学在小儿肺动脉高压（PAH）中的作用及其与右心室（RV）功能障碍的关系在很大程度上被忽视。在此，我们与临床前 PA-带状 (PAB) 小鼠模型相比，描述了 RV-肺动脉 (PA) 轴维持压力超负荷对儿科 PAH 患者心肌应变和左心室 (LV) 力学的影响。我们假设 PAB 小鼠模型模拟了儿科 PAH 心室间力学的重要方面，并且可能有益于作为一些在儿童中不可能进行的纵向和介入研究的替代模型。使用 CMR 特征跟踪 (FT) 软件对 18 名 PAH 和 17 名健康（对照）儿科受试者的平衡稳态自由进动 (bSSFP) 心血管磁共振 (CMR) 图像进行回顾性分析，以计算心肌应变的测量结果。此外，还使用谐波相流分析对每个受试者的心肌标记 CMR 图像进行分析，以得出左心室扭转率。在 CMR 后 48 小时内，PAH 患者接受右心导管插入术 (RHC)，以测量 PA/RV 压力，并计算 RV 收缩末期弹性（RV_Ees，一种与负荷无关的收缩力的测量方法）。对小鼠进行 PAB 手术以诱导右心室压力超负荷和心肌重塑。手术后 7 周，对 12 只 PAB 小鼠和 9 只对照小鼠（Sham）进行 bSSFP-CMR、标记 CMR 和心内导管插入术，并进行与上述患者研究相同的后处理。 RV_Ees 通过单搏法进行评估。在高血压条件下，PAB 小鼠 (p = 0.004) 和儿童 PAH 患者 (p < 0.001) 的左心室扭转率均显着降低。 PAB (r = 0.91, p = 0.05) 和 PAH 受试者 (r = 0.51, p = 0.04) 中 LV 扭转率的降低与 RV_Ees 的降低显着相关。为了比较 LV 扭转率和应变参数的组合指标，使用了主成分分析 (PCA)。 PCA 显示 PAH 患者分组为 PAB 小鼠，对照组分组为 Sham 小鼠。与左心室扭转率相似，PAB 小鼠和患有 PAH 的儿童在高血压条件下，左心室整体峰值周向、径向和纵向应变均显着降低 (p<0.05)。 PAB 小鼠模型类似于 PAH 相关心肌力学，可能为研究 RV/LV 相互依赖性机制提供潜在模型。在线版本包含可在 10.1186/s12968-021-00759-8 获取的补充材料。
The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV–pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children. Balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) images of 18 PAH and 17 healthy (control) pediatric subjects were retrospectively analyzed using CMR feature-tracking (FT) software to compute measurements of myocardial strain. Furthermore, myocardial tagged-CMR images were also analyzed for each subject using harmonic phase flow analysis to derive LV torsion rate. Within 48 h of CMR, PAH patients underwent right heart catheterization (RHC) for measurement of PA/RV pressures, and to compute RV end-systolic elastance (RV_Ees, a measure of load-independent contractility). Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. bSSFP-CMR, tagged CMR, and intra-cardiac catheterization were performed on 12 PAB and 9 control mice (Sham) 7 weeks after surgery with identical post-processing as in the aforementioned patient studies. RV_Ees was assessed via the single beat method. LV torsion rate was significantly reduced under hypertensive conditions in both PAB mice (p = 0.004) and pediatric PAH patients (p < 0.001). This decrease in LV torsion rate correlated significantly with a decrease in RV_Ees in PAB (r = 0.91, p = 0.05) and PAH subjects (r = 0.51, p = 0.04). In order to compare combined metrics of LV torsion rate and strain parameters principal component analysis (PCA) was used. PCA revealed grouping of PAH patients with PAB mice and control subjects with Sham mice. Similar to LV torsion rate, LV global peak circumferential, radial, and longitudinal strain were significantly (p < 0.05) reduced under hypertensive conditions in both PAB mice and children with PAH. The PAB mouse model resembles PAH-associated myocardial mechanics and may provide a potential model to study mechanisms of RV/LV interdependency. The online version contains supplementary material available at 10.1186/s12968-021-00759-8.
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DOI：
10.1016/j.echo.2013.10.002
发表时间：
2014-01-01
影响因子：
6.5
作者：
Kaku, Kyoko;Takeuchi, Masaaki;Otsuji, Yutaka
通讯作者：
Otsuji, Yutaka
DOI：
10.1115/1.4042682
发表时间：
2019-05-01
影响因子：
1.7
作者：
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通讯作者：
Shandas, Robin
DOI：
10.1152/ajpheart.1997.272.2.h1053
发表时间：
1997-02-01
影响因子：
4.8
作者：
Desai, KH;Sato, R;Bernstein, D
通讯作者：
Bernstein, D
DOI：
10.1164/rccm.201607-1515pp
发表时间：
2017-03-01
影响因子：
24.7
作者：
Bonnet, Sebastien;Provencher, Steeve;Humbert, Marc
通讯作者：
Humbert, Marc
影响因子：
20.1
作者：
MIYAUCHI, T;YORIKANE, R;GOTO, K
通讯作者：
GOTO, K