【作者】 王丽平；

【导师】 徐卓明；

【作者基本信息】 上海交通大学 ， 儿科学， 2020， 硕士

【摘要】 目的先天性心脏病相关性肺高压(Pulmonary Hypertension Related to Congenital Heart Disease,PH-CHD)是肺循环血流动力学异常所致的一种疾病,长期异常的肺血流动破坏血管内皮细胞结构和功能,使肺血管发生不可逆性病变,甚至导致右心衰竭和死亡。因此,明确PH-CHD患儿肺血管内皮损伤严重程度及其相关血流动力学特性,有助于揭示影响PH-CHD发生发展的血流动力学机制,从而从根源上控制、改善和治疗PH-CHD。本研究将从肺血管内皮损伤和血流动力学特性两个方面,探索可用于PH-CHD无创性诊断评估的指标,以期为临床诊疗提供参考。方法纳入70例先天性心脏病患儿,根据术前心脏超声所测肺动脉收缩压(Systolic Pulmonary Arterial Pressure,sPAP)分为正常组、疑似组和确诊组,并随访其术后6个月sPAP是否大于50 mmHg,将其分为可逆组和不可逆组。采集其血标本进行内皮损伤特异性标记物检测,并根据患儿临床信息和血液标记物结果进行PH-CHD可逆性危险分层评分。同时,收集10例正常和10例PH-CHD患儿临床影像资料,利用计算流体动力学方法进行肺血流运动模拟,探寻PH-CHD特异性流体特性。结果PH-CHD患儿外周血循环内皮细胞(Circulating Endothelial Cells,CECs)和内皮素-1(Endothelin-1,ET-1)明显高于正常组和疑似组,外周血内皮型一氧化氮合酶(Endothelial Nitric Oxide,e NOS)在PH-CHD确诊组和疑似组明显升高,与正常组有统计学差异。不可逆性组外周血CECs明显高于可逆性组;ET-1和eNOS在两组间无明显统计学差异。ROC曲线显示危险分层评分对PH-CHD诊断价值较高。流体力学分析显示PH-CHD患儿主肺动脉增粗,肺动脉入口流量和分支流速升高,主肺动脉壁面切应力(Wall Shear Stress,WSS)降低,体表面积标准化能量损失(?)增加。结论内皮损伤特异性血液标记物CECs、eNOS和ET-1,流体力学参数WSS和(?)与PH-CHD密切相关。术前CECs及危险分层评分可反映PH-CHD是否可逆。更多还原

【Abstract】 Objective Hemodynamic disorder of the pulmonary circulation is the main cause of pulmonary hypertension related to congenital heart disease(PH-CHD).Abnormal hemodynamics of the pulmonary circulation gradually destroys the structure and function of endothelial cells,leading to irreversible lesion of the pulmonary vascular and even right heart failure and death.Thus,identifying the severity of endothelial injury and the hemodynamic characteristics in patients with PH-CHD is conducive to understanding the hemodynamic mechanism of PH-CHD,which will greatly benefit the control,improvement and treatment of the disease.This study aims to explore the noninvasive indicators for the assessment of PH-CHD from the aspect of endothelial biomarkers and hemodynamic characteristics of the pulmonary artery,so as to provide more detailed information for clinical designing making.Method Seventy CHD patients were enrolled in this study.Based on the preoperative systolic pulmonary arterial pressure(s PAP),they were divided into normal,suspected and PH-CHD groups.These patients were followed up for 6 months after surgery,and were split into reversible and irreversible groups according to the sPAP.Their blood samples were collected for the detection of circulating endothelial cells(CECs),endothelin-1(ET-1)and endothelial nitric oxide(eNOS).Reversible risk stratification of PH-CHD was performed according to the clinical information and endothelial injury biomarkers.Meanwhile,the CT data of ten PH-CHD patients and ten matched control subjects were collected.Based on the imaging data,computational fluid dynamics(CFD)were used to analyze patient-specific hemodynamic parameters.Results Biomarkers of endothelial injury showed that CECs and ET-1 in PH-CHD group was increased significantly than that in normal and suspected groups.e NOS was increased significantly in the PH-CHD and suspected groups,which were statistically different from the normal group.CECs in the irreversible group was significantly higher than that in the reversible group.There’s no statistical difference between the irreversible and reversible groups in ET-1 an e NOS.ROC curve showed that the risk stratification is of high diagnostic value for reversibility evaluation.Morphological analysis indicated that the main pulmonary artery(MPA)size was increased in PH-CHD patients.Hemodynamic results showed that the velocity was higher in the pulmonary artery(PA)branches of PH-CHD patients,in whom PA flow rate usually increased.Wall shear stress(WSS)in the MPA was lower and body surface area normalized energy loss(?)was higher in PH-CHD patients.(?) was positively correlated with PA morphology and flow rate.(?) was a sensitive indicator in the diagnosis of PH-CHD.Conclusion Biomarkers of CECs,e NOS and ET-1,hemodynamic parameters of WSS and (?) were closely related with PH-CHD.In addition,CECs count and risk stratification have highly practical value in assessing the reversibility of PH-CHD.更多还原