三维斑点追踪显像评估压力负荷升高右室心肌力学改变及机制初探

A variety of cardiovascular diseases may result in right ventricular(RV) acute or chronic pressure overload(aPO or cPO), RV myocardial function is strongly associated with illness progression and prognosis.We have no effective method for the early assessment of RV myocardial function in the clinical practice. Previous studies have demonstrate that RV myocardial biomechanics may have changed using two-dimensional speckle tracking imaging(STI) although RV global function is normal in the setting of pressure overload. However, two-dimensional STI is limited by two-dimensional plane. Moreover, the correlation between RV myocardial biomechanics and histological, and cellular and molecular mechanism is unknown. Recently, three-dimensional STI (3D-STI)can identify early left ventricular myocardial biomechanics abnormalities, but the application of 3D-STI in RV has not been reported. Therefore, we assume that early RV myocardial biomechanics abnormalities in RV pressure overload can be assessed by 3D-STI. We will confirm the accuracy of 3D-STI by exploring the correlation between the 3D-STI parameters and serology, RV hemodynamic by right heart catheter, cardiac magnetic resonance imaging, myocardial pathomorphology, and cellular and molecular mechanism in the experimental and clinical studies. Furthermore, we will further elaborate the histological and molecular biology basis of RV myocardial biomechanics abnormalities, and clarify the clinical significance of 3D-STI in patients with acute pulmonary embolism and chronic pulmonary artery hypertension.The aim of this study is to provide the novel method for early detecting RV myocardial function impairement, assessing therapeutic effect and judging prognosis in patients with RV aPO and cPO.

多种心血管疾病可致右室急性或慢性压力负荷升高（aPO或cPO），右室心肌功能改变与其病情进展及预后密切相关。目前临床缺乏早期评估右室心肌功能的有效方法。我们前期研究采用二维斑点追踪显像（STI）技术发现cPO时尽管右室整体功能正常，但其心肌力学已发生改变。但二维STI局限于二维平面，而且右室心肌力学与组织学、细胞分子变化关系尚不清楚。新近研究表明三维STI（3D-STI）可早期显示左室心肌力学改变,但未见应用于右室的报道。因此我们假设3D-STI可评价压力负荷升高所致的右室心肌力学早期改变，通过实验和临床研究，与血清学、血流动力学、核磁共振、心肌病理、细胞分子机制比较来验证该方法的准确性。本研究进一步阐明右室心肌力学改变的组织学及分子生物学基础，进一步明确3D-STI在急性肺栓塞及慢性肺动脉高压患者中的临床意义，旨在为早期发现右室心肌功能受损、有效评估疗效及判断预后提供一种新方法。

目的：应用三维斑点追踪成像技术（3D-STI）评价压力负荷过重右室局部和整体形变，探讨3D-STI参数与血流动力学、心肌病理、核磁共振参数的相关性，进一步明确其临床意义。方法：实验研究：肺动脉环缩法（PAB）用于建立右室压力负荷过重犬模型，3D-STI技术评价肺动脉环缩术后3月实验组与假手术组右室局部和整体功能，右室3D-STI参数包括纵向、环向及径向应变。动物处死后右室心肌用于组织病理和分子机制研究。临床研究：选取肺高压患者60例，急性肺栓塞患者20例，对照组25例，3D-STI技术评价肺高压和急性肺栓塞患者右室功能，心脏核磁共振评估右室容积和射血分数，6-分钟步行距离评估患者运动耐力，血流动力学参数由超声评估。结果：右室压力负荷过重导致右室肥厚、间质纤维化及毛细血管密度减低。与假手术组相比，PAB组右室整体纵向应变减低，而整体径向及环向应变未改变。PAB组基因HIF1α、CX43、VEGF、bcl-2较假手术组（Sham）组降低，caspase-3较Sham组升高。PAB组蛋白P53、caspase-3较Sham表达升高，蛋白HIF1α、VEGF、CX43及bcl-2较Sham组表达降低。右室压力负荷过重模型右室3D-STI参数与血流动力学、心肌组织病理，分子细胞机制相关；肺高压患者和肺栓塞患者右室纵向、径向及环向应变减低。右室3D-STI参数与核磁共振测得右室射血分数、血流动力学及6分钟步行距离相关。治疗后6月只有纵向应变改善。右室纵向应变、年龄及射血分数是不良临床结局的预测因子。结论：右室压力负荷过重表现为右室3D-STI参数减低，3D-STI技术为临床右室急性或慢性压力负荷升高两种状态下患者的病情评估、疗效监测及预后判断提供了新的无创性指标。