基于实时三维超声的右心室节段性重构在肺高压右心室-肺动脉失耦联中的作用和机制

Pulmonary hypertension (PH) is a physiological disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Right ventricular (RV) remodeling is a major determinant of ventricular–arterial uncoupling （VAu） and right heart failure in patients with PH. However, the role and mechanism of RV regional remodeling in VAu in PH remains unclear. Our pilot studies comfirmed the accuracy and reproducibility of real-time three-dimensional Echocardiography(RT3DE) in the evaluation of RV regional volume and systolic function. We found that RT3DE-derived RV function parameters are less preload-dependent than two-dimensional ones. RT3DE-derived RV regional systolic function was sensitive to describe early RV regional remodeling in animal PH models. RT3DE-derived RV regional volume and systolic function were closely related to RV afterload and patient outcome. We hypothesized that RT3DE-derived RV regional remodeling might be a potential sentinel parameter in the development of in VAu. We apply for the approval of this present study, aiming to: ① detect the difference and dynamic evolution of RT3DE-based RV regional remodeling under the two status of ventricular–arterial coupling (VAc) and VAu in patients with PH and canine models, ② explore the regional difference of cardiomyocyte apoptosis and interstitial fibrosis of the RV muscle in canine models and patients with PH under the two status of VAc and VAu, ③ explore the relationship between RT3DE parameters and hemodynamic parameters measured by right heart catheter and interstitial fibrosis measured by late gadolinium enhanced cardiovascular magnetic resonance. The results of this present study might provide new echocardiographic parameters in the early dignosis of VAu and prognosis prediction in patients with PH.

肺高压 (PH)是多病因且严重威胁人类健康的病征。右心室（RV）重构与PH右心室-肺动脉失耦联（VAu）及右心功能衰竭密切相关。但目前RV节段性重构在VAu中的作用和机制尚不清楚。我们的前期研究显示实时三维超声心动图（RT3DE）在RV节段容积及收缩功能评价中准确性高，容量负荷依赖性低，能早期反映PH动物模型RV节段性重构，并与压力负荷及预后密切相关。我们提出基于RT3DE的RV节段性重构可能是PH患者VAu的哨兵参数假说，拟在动物实验和临床研究中，使用RT3DE检测PH右心室-肺动脉耦联（VAc）及VAu状态下RV节段性重构的不同特征及演变规律，从PH动物模型和患者节段心肌细胞凋亡和间质纤维化的角度探索RV节段性重构的发生机制，分析RT3DE参数与组织病理、右心导管血流动力学参数及磁共振钆延迟显像之间的相关性，探索能够早期诊断PH患者VAu并有助于预后预测的超声新指标。

肺高压 (PH)是多病因且严重威胁人类健康的病征。右心室（RV）重构与PH右心室-肺动脉失耦联（VAu）及右心功能衰竭密切相关。目前RV节段性重构在VAu中的作用和机制尚不清楚。我们的前期研究显示实时三维超声心动图（RT3DE）在RV节段容积及收缩功能评价中准确性高，容量负荷依赖性低，能早期反映PH动物模型RV节段性重构，并与压力负荷及预后密切相关，由此我们提出基于RT3DE的RV节段性重构可能是PH患者VAu的哨兵参数假说。在本研究中，目前已完成比格犬PH模型及PH患者右心室节段容积与收缩功能变化特征的相关研究，通过已完成的研究内容，我们发现RT3DE能够有效运用于PH患者 VAc及VAu状态下右心室节段性重构的评估，不同病因相关的PH右心室节段性重构具有不同特征及演变规律，VAu状态下右心室体部节段心肌细胞凋亡较其他部位更为显著，基于RT3DE的右心室体部节段形态与功能重构在VAc状态下即出现变化，在VAu状态下变化进一步加剧，并与右心室整体功能密切相关，可能是早期诊断PH患者VAu并有助于预后预测的超声新指标。本研究结果提示RT3DE在PH患者右心室节段收缩功能评估中有潜在的应用价值，有望为PH患者病情评估提供新的无创性指标，为其他病理生理状态下右心室功能评价提供研究基础和新思路。