【作者】 张静；

【导师】 谢明星；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2008， 博士

【摘要】 自1953年Gibbon应用垂屏式氧合器和滚压泵在心脏直视下成功手术修复1例房间隔缺损以来[1],体外循环心脏直视手术已成为心脏外科的主要治疗手段,成功矫治了许多先天性及后天获得性心脏疾患,为患者赢得了宝贵的生存机会。但体外循环心脏直视术后,机体循环系统重新启动及加载运行,常导致患者血流动力学状态发生急剧改变。同时,手术本身的不利影响,如体外循环非生理性灌注触发的全身炎症反应综合征、术中心肌的缺血再灌注损伤、手术本身的机械损伤等多种因素,常导致术后心肌发生严重损伤。研究表明:体外循环心脏直视术后有相当比例患者发生低心排血量综合征、心力衰竭、各种心律失常等严重并发症,从而影响患者的预后与存活。因此,早期识别心脏手术后患者心脏功能情况,对指导临床医师采取及时合理的医疗措施,预防严重并发症的发生及改善预后具有重要临床意义。影响心功能的因素有很多,主要有心室形态、前、后负荷、心肌收缩力、心肌收缩同步性、心率等。超声心动图技术因其简便无创、价格低廉、可床边重复使用等优点受到临床医师的青睐,目前已成为监测心脏术后心功能的主要影像学方法。左室射血分数（left ventricular ejection fraction）及短轴缩短率（fraction shortening）是常用的评价左室收缩功能的指标,但其仅能初步反映左室整体功能情况,并显著受心室负荷状态的影响,不能对具有三维运动的心脏的局部心肌运动特征进行全面分析[5-7]。新近开发的二维斑点追踪显像技术,通过实时追踪心肌内超声斑点回声的空间运动获得心肌运动信息,无角度和帧频依赖性,可对任何超声切面进行分析,能同时定量评价心肌在纵向、轴向及环向方向上的运动力学特征,从而能对整体和局部心肌的运动和功能进行全面评价。室间隔缺损（ventricular septal defect, VSD）是儿童最常见的先天性心脏病,占所有先天性心脏病的25%左右。国内自1958年6月开展体外循环下VSD修补术,如今单纯VSD手术成功率已达90%以上,成为VSD的主要治疗手段。外科VSD修补术也是最常见的小儿心脏外科手术之一。因此,本研究以VSD修补术为例,应用二维斑点追踪显像技术对VSD修补术后早期左室形态、左室心肌收缩同步性及左室局部心肌收缩功能进行全面定量分析,以探讨体外循环心内直视手术对左室功能的影响。本研究分以下三部分:第一部分二维超声心动图评价VSD修补术对围术期左室构形的影响本部分以拟行VSD修补术的患儿作为研究对象,根据VSD大小,将其分为三组:大、中、小VSD组。应用二维超声心动图对术前及术后6h内的左室形态特征进行全面分析,以探讨体外循环心内直视手术对VSD患儿左室构型的影响。结果显示:①各VSD组术前与对照组相比:小VSD组收缩末期与舒张末期以体表面积标化的左室长轴长径（Ld、Ls）、短轴前后径（APd、APs）、侧壁间隔横径（LSd、LSs）;左室长轴构型指标SIs、SId、[（D1+D2+D3）/3L]d、[（D1+D2+D3）/3L]s、[2 D1/L]d、[2 D1/L]s、FSL、FSD2及短轴构型指标LSd/APd、LSs/APs、FSLS、FSAP测值与对照组相比差异均无统计学意义;中VSD组及大VSD组Ld、Ls、LSd、LSs、APd、APs、SIs、[（D1+D2+D3）/3L]d、[2D1/L]d、FSD2、FSLS测值均显著高于对照组（P<0.05 or <0.01）;SId、[（D1+D2+D3）/3L]s、[2 D1/L]s、LSs/APs测值显著低于对照组（P<0.05）,FSAP、LSd/APd测值与对照组相比差异无统计学意义。中VSD组FSL测值与对照组相比差异无统计学意义,而大VSD组FSL测值显著低于对照组（P<0.05）。②各VSD组术后与术前相比:小VSD组术后除Ld、Ls、LSd、APd、[2 D1/L]d、FSLS测值显著低于术前外（P<0.05）,其余各指标测值术前、术后相比差异无统计学意义。中VSD组及大VSD组术后Ld、Ls、LSd、APd、APs、LSd/APd、SIs、[（D1+D2+D3）/3L]d、[2 D1/L]d、FSD2、FSLS测值显著低于术前,SId、[（D1+D2+D3）/3L]s、[2 D1/L]s、LSs/APs显著高于术前,组间比较差异均有统计学意义（P<0.05）,其余指标测值术前、术后相比差异无统计学意义。③对照组与各VSD组术后相比:小VSD组上述各指标测值与对照组相比差异无统计学意义。中VSD组除FSLS、FSAP测值显著低于对照组,LSs、APs测值显著高于对照组外,其余各指标测值两组间比较差异无统计学意义。大VSD组除Ld、SIs、LSd、APd、LSs、APs、[（D₁+D₂+D₃）/3L]d、[2 D₁/L]d测值显著高于对照组,[（D₁+D₂+D₃）/3L]s、[2 D₁/L]s、LSd/APd、LSs/APs、FSLS、FSAP测值显著低于对照组外（P<0.05）,其余各指标测值两组间比较差异无统计学意义。第二部分斑点追踪显像技术评价VSD修补术对围术期左室心肌收缩同步性的影响本部分以拟行VSD修补术的患儿作为研究对象,根据VSD大小,将其分为三组:大、中、小VSD组。应用斑点追踪显像技术结合应变参数对VSD修补术前及术后6h内左室心肌收缩同步性进行评价,以探讨体外循环心内直视手术对患儿左室心肌收缩同步性的影响,并探讨斑点追踪显像技术在心脏手术围手术期评价患者左室心肌收缩同步性的价值。结果显示:①各VSD组术前与对照组相比:小VSD组左室各节段心肌纵向、轴向及环向收缩期达峰值应变时间标准差（Tsl-SD、Tsr-SD、Tsc-SD）及最大差值（Tsl-diff、Tsr-diff、Tsc-diff）测值与对照组相比差异无统计学意义。中VSD组除Tsl-SD、Tsl-diff测值显著高于对照组外（P<0.05）,其余各指标测值两组间比较差异无统计学意义。大VSD组Tsl-SD、Tsl-diff、Tsc-SD、Tsc-diff测值均显著高于对照组相应测值（P<0.05）,而Tsr-SD、Tsr-diff测值与对照组相比差异无统计学意义。小、中VSD组左室各室壁中间段心肌最小Tsl、Tsc、Tsr测值与最大测值比较差异无统计学意义。大VSD组相应最小测值与最大测值相比差异有统计学意义（P<0.05）。三组最大测值均位于前间隔或后间隔部位。②各VSD组术后与术前相比:小VSD组术后各指标测值与术前相比差异无统计学意义。中VSD组及大VSD组术后各指标测值与术前相比均显著增加,差异有统计学意义（P<0.05）。③对照组与各VSD组术后比较:小VSD组术后各指标测值与对照组相比差异均无统计学意义。中VSD组及大VSD组上述各指标测值均显著大于对照组相应测值,组间比较差异有统计学意义。术后小VSD组左室各室壁中间段心肌最小Tsl、Tsc、Tsr测值与最大测值相比差异无统计学意义。而中VSD组及大VSD组相应最小测值与最大测值相比差异均有统计学意义（P<0.05）,且最大测值均位于前间隔或后间隔。第三部分斑点追踪显像技术评价VSD修补术对围术期左室局部心肌收缩功能的影响本部分以拟行VSD修补术的患儿作为研究对象,根据VSD大小,将其分为三组:大、中、小VSD组。应用斑点追踪显像技术结合应变及应变率参数对VSD修补术前、术后6h内左室局部心肌收缩功能进行评价,以探讨体外循环心内直视手术对患儿左室局部心肌收缩功能的影响,并探讨斑点追踪显像技术在心脏手术围手术期评价患者左室局部心肌收缩功能的价值。结果显示:①各手术组术前与对照组相比:小VSD组左室舒张末期容积（LVEDV）、收缩末期容积（LVESV）、左室射血分数（LVEF）测值与对照组相比差异无统计学意义;中VSD组LVEDV测值显著高于对照组（P<0.05）,LVESV、LVEF测值与对照组相比差异无统计学意义。大VSD组LVEDV、LVESV测值显著高于对照组（P<0.05）,LVEF测值与对照组相比差异无统计学意义。小VSD组左室各节段心肌纵向,轴向,环向应变（SL、SR、SC）及应变率（SrL、SrR、SrC）测值与对照组相比差异无统计学意义。中VSD组左室各节段心肌SL、SR、SC、SrL、SrR、SrC测值均显著高于对照组,组间比较差异有统计学意义（P<0.05）。大VSD组左室各节段心肌SL、SrL测值显著低于对照组（P<0.05）,SR、SC、SrR、SrC测值前壁、后壁及下壁各节段心肌显著低于对照组相应节段测值（P<0.05）,而前间隔、侧壁及后间隔各节段心肌上述指标测值与对照组相比,差异无统计学意义。②各VSD组术后与术前相比:小VSD组术后LVEDV、LVESV、LVEF测值与术前相比差异无统计学意义。中VSD组及大VSD组术后LVEDV、LVESV、LVEF测值均显著低于术前,组间比较差异均有统计学意义（P<0.01）。小VSD组术后左室各节段心肌SL、SR、SC、SrL、SrR、SrC测值均显著低于术前,其中以前间隔、后间隔及下壁降低尤为明显（P<0.01）。中VSD组及大VSD组术后左室各节段心肌SL、SR、SC、SrL、SrR、SrC均显著低于术前相应节段测值,差异有统计学意义（P<0.01）。③各手术组术后与对照组相比:小VSD组及中VSD组术后LVEDV、LVESV、LVEF测值与对照组相比,差异无统计学意义;大VSD组LVEDV、LVESV测值显著高于对照组（P<0.05）,LVEF测值显著低于对照组（P<0.05）。小、中、大VSD组左室各节段心肌SL、SR、SC、SrL、SrR、SrC测值均显著低于对照组（P<0.01）。结论在本研究条件下,我们可以得出如下结论:1. VSD修补术后早期左室构型即发生改变:左室长轴方向上,舒张末期左室构型由术前的类圆形趋向椭圆型,而收缩末期由术前狭长的扁椭圆形趋向圆椭圆形。左室短轴方向上,舒张末期左室构型仍保持为类圆形,而收缩末期由术前的椭圆形趋向类圆形,即大、中、小VSD组术后左室构型均趋于正常化。小VSD组术后早期左室构型即可完全恢复正常,而中、大VSD组围手术期左室构型尚不能完全恢复至正常。2. VSD修补术对小VSD左室心肌收缩同步性未产生明显影响,对中VSD及大VSD左室心肌产生不利影响,导致左室心肌收缩显著不同步。3.二维斑点追踪显像技术结合应变参数可以对VSD修补术前、术后左室心肌收缩同步性进行全面评价。3.大、中、小VSD修补术后左室节段心肌收缩功能均显著低于术前,其降低的原因不仅与VSD术后前负荷显著改变有关,还与手术过程导致左室构型改变、左室心肌收缩不同步及心肌收缩力损害有关。4.与常规超声心动图技术相比,二维斑点追踪显像技术结合应变及应变率参数可准确、定量评价术后局部心肌收缩功能。应变及应变率参数是负荷依赖性参数,测值受前、后负荷变化的影响,不能准确反映局部心肌收缩力情况,但通过对比分析,仍能从中得出心肌收缩力的变化信息。更多还原

【Abstract】 Since open-heart surgery with cardiopulmonary bypass （CPB） began with closure of an atrial septal defect by John Gibbon in 1953[1], the CPB have been applied widely in the field of cardiac surgery. Cardiac surgery with CPB has been used to correct many cardiac abnormalities for congenital or acquired heart diseases, and provide opportunity for survival, but it is also associated with a defined degree of preoperative and postoperative morbidity and mortality related severe complication, such as low cardiac output syndrome, arrhythmias, heart failure. Potential mechanisms have included the significant change of hemodynamics immediate after operation and the procedures themselves, such as CPB related systemic inflammatory response syndrome, direct surgical aggression on the heart tissue, injury effect of hypothermia and/or ischemia and reperfusion . Identification of patients who are at higher risk may allow better targeting of investigation, monitoring, and treatment, ultimately leading to an improvement in patient outcome.The important determinants of left ventricular （LV） systolic function are ventricular geometry, preload, afterload, contractility, synchrony of contraction and heart rate . Echocardiography is considered to be an ideal tool for LV function assessment. Among the several LV function echocardiographic indexes, the most commonly used in the clinical setting are LV ejection fraction （EF） and shortening fraction （FS）. However, EF and FS are load-dependent parameters and may not reflect the regional myocardium contractile function.A novel approach to quantify regional LV function from routine gray-scale 2D echocardiographic images, known as speckle tracking （STE）, calculates myocardial strain independent of angle of incidence. The software uses conventional gray-scale B-mode recordings and tracks myocardial speckles, which serve as natural acoustic markers. Myocardium multi-dimensional, i.e. longitudinal, radial and circumferential deformation can be measured from echocardiographic views. Experimental and clinical studies have demonstrated that the SET method can assess the LV regional and global contractile alterations accurately in healthy subjects, in the settings of acute and chronic ischemia, dyssynchrony, and cardiomyopathy .Ventricular septal defects （VSD） are a common congenital heart disease, and their repair is one of the most representative cardiac operations. In this study, we used the STE technique to evaluate the effect of cardiac surgery with CPB on the LV geometry, LV regional and global contractile synchrony and function associate with VSD surgery. The study was divided into three parts as follows:Part 1. Assessment of left ventricular geometry during perioperation of VSD surgery using 2D echocardiographyThe aim of this part was to assess the effect of cardiac surgery with CPB on the LV geometry associate with the repair of VSD using 2D echocardiography. The VSD surgical patients were involved in this study. The patients were divided into three groups according the size of the VSD: small （S）, moderate （M） and large （L） group.Results:①pre-operation: compared with the values in the control group, the LV end-systolic and end-diastolic longest diameter （Ls, Ld） in longitudinal section, radial anterior to posterior diameter （APs, APd）, and lateral to septal diameter （LSs, LSd） in cross section, sphericity index （SIs, SId）, [（D₁+D₂+D₃）/3L]d、[（D₁+D₂+D₃）/3L]s、[2D₁/L]d、[2D₁/L]s, LSd/APd, LSs/APs, and fractional shortening of L, D₂, LS, AP （FSL, FSD₂, FSLS, FSAP） showed no significant difference in the S VSD group. Ld, Ls, LSd, LSs, APd, APs, SIs, [（D₁+D₂+D₃）/3L]d, [2D₁/L]d, FSD₂, FS_LS increased significantly （P<0.05 or 0.01）, SId, [（D₁+D₂+D₃）/3L]s, [2D₁/L]s, LSs/APs decreased significantly and FS_AP, LSd/APd showed no significant difference in the M VSD and L VSD groups. FSL showed no significant difference in the M VSD group, and FSL decreased significantly in the L VSD group （P<0.05）.②within 6 hours after the operation, the Ld, Ls, LSd, APd, [2 D1/L]d, FSLS significantly lower than that before operation in the S VSD group （P<0.05）, the others parameters showed no significant difference when compared with the preoperation. Ld, Ls, LSd, APd, APs, LSd/APd, SIs, [（D₁+D₂+D₃）/3L]d, [2 D₁/L]d, FSD₂, FSLS were significantly lower （P<0.05） and SId, [（D₁+D₂+D₃）/3L]s, [2 D₁/L]s, LSs/APs were significantly higher （P<0.05） than those before operation in the M and L VSD groups, the others parameters showed no significant difference between the preoperation and postoperation.③postoperation: Compared with the values in the control group, all the parameters showed no significant differences in the S VSD group. The FSLS, FSAP decreased significantly （P<0.05）, LSs, APs increased significantly （P<0.05）, and the other parameters showed no significant differences in the M VSD group. The Ld, SIs, LSd, APd, LSs, APs, [（D₁+D₂+D₃）/3L]d, [2 D₁/L]d values increased significantly （P<0.05）, [（D₁+D₂+D₃）/3L]s, [2 D₁/L]s, LSd/APd, LSs/APs, FSLS, FSAP values decreased significantly （P<0.05）, and the other parameters showed no significant differences in the L VSD group.Part 2. Assessment of LV regional and global contractile synchrony during perioperation of VSD surgery using speckle tracking echocardiographyThe aims of this part were to assess the effect of cardiac surgery with CPB on the LV regional and global contractile synchrony associate with the repair of VSD using speckle tracking echocardiography combined with strain parameter, and to assess the value of speckle tracking echocardiography in the evaluation of LV contractile synchrony during perioperation. The VSD surgical patients were involved in this study; the patients were divided into three groups according the size of the VSD: small （S）, moderate （M） and large （L） group.Results:①preoperation: Compared with the values in the control group, the standard deviation of the time to peak systolic longitudinal strain （Tsl）, peak systolic radial strain （Tsr） and peak systolic circumferential strain （Tsc） in all segments （Tsl-SD, Tsr-SD, Tsc-SD） and the maximal temporal difference of Tsl, Tsr, Tsc （Tsl-diff, Tsr-diff, Tsc-diff） in all segments showed no significant differences in the S group. The Tsl-SD, Tsl-diff increased significantly （P<0.05）, and the other parameters showed no significant differences in the M VSD group. The Tsl-SD, Tsl-diff, Tsc-SD, Tsc-diff increased significantly （P<0.05）, and the other parameters showed no significant difference in the L group. The longest Tvl, Tvr and Tsc occurred in the antero-septal or septal segments in all three groups.②within 6 hours after the operation, the all parameters showed no significant difference as compared with the preoperation in the S VSD group. All the parameters were higher significantly in the M and L groups than those before operation （P<0.05）.③postoperation: Compared with the values in the control group, the all parameters showed no significant difference in the S VSD group. All the parameters increased significantly in the M and L VSD groups （P<0.05）. The longest Tvl, Tvr and Tsc occurred in the antero-septal or septal segments in all three groups.Part 3. Assessment of LV regional and global contractile function during perioperation of VSD surgery using speckle tracking echocardiographyThe aims of this part were to assess the effect of cardiac surgery with CPB on the LV regional and global contractile function associated with the repair of VSD using speckle tracking echocardiography combined with strain and strain rate parameters, and to assess the value of speckle tracking echocardiography in the evaluation of LV contractile function during perioperation. The VSD surgical patients were involved in this study; the patients were divided into three groups according the size of the VSD: small （S）, moderate （M） and large （L） group.Results:①preoperation: Compared with the values in the control group, the LV end-distolic volume （LVEDV）, end-systolic volume （LVESV）, and LV ejection fraction （LVEF） showed no signigicant difference in the S VSD group; the LVEDV increased significantly （P<0.05） and LVESV, LVEF showed no significant difference in the M group; the LVEDV, LVESV increased significantly （P<0.05） and LVEF showed no significant difference in the L group. The longitudinal strain （SL）, radial strain （SR）, circumferential strain （SC）, and longitudinal strain rate （SrL）, radial strain rate （SrR）, and circumferential strain rate （SrC） in all segments showed no significant difference in the S VSD group; the SL, SR, SC, SrL, SrR, SrC values in all segments increased significantly（P<0.05） in the M VSD group; the SL, SrL values decreased significantly（P<0.05） in all segments and the SR, SC, SrR, SrC decreased significantly in anterior, posterior, and inferior walls （P<0.05） and showed no significant difference in anter-septal, septal, lateral walls in the L VSD group.②within 6 hours after the operation, compared with the values before operation, the LVEDV, LVESV, LVEF showed no significant difference in the S VSD group; The LVEDV, LVESV and LVEF decreased significantly in the M and L VSD groups （P<0.01）. The SL, SR, SC, SrL, SrR, SrC in all segments decreased significantly in the three groups （P<0.05 or <0.01）.③postoperation: Compared with the values in the control group, the LVESV, LVEDV, and LVEF showed no significant difference in the S and M VSD groups, the LVEDV, LVESV increased significantly and LVEF decreased significantly in the L VSD group （P<0.05）. The SL, SR, SC, SrL, SrR, SrC decreased significantly in all segments in the three groups （P<0.01）.Conclusions:Based on the present study, our conclusions are as follows:①The LV dynamic geometry changed and trended to normalize in the early postoperative period. In longitudinal section, the LV is more elliptical in the end-diastole and more spherical in the end-systole as compared with preoperation. In cross section, the LV geometry did not changed in the end-diastole, was still circular, similar to the preoperation, but it changed from elliptical model of preoperation to spherical model after operation in the end-systole. The LV geometry was normalizing immediately after operation in the S VSD group, and was gradual normalizing over time after operation in the M and L groups.②VSD repair had no significant effect on the LV regional and global contractile synchrony in the S VSD group, but it impaired the LV contractile synchrony in the M and L VSD groups.③Speckle tracking echocardiography combined with strain parameter can assess accurately the change of LV regional and global contractile synchrony during perioperation of cardiac surgery.④The VSD repair impaired the LV regional and global contractile function immediately after operation in the three groups. We presumed that reduction in LV preload and myocardium injury related the procedures themselves were the primary causes.⑤Speckle tracking echocardiography combined with strain and strain rate parameters can assess accurately the change of LV regional and global contractile function during perioperation of cardiac surgery. Strain and strain rate are also load-dependent parameters and may not reflect the true myocardial contractile status, but it can demonstrate the presence of early abnormalities of myocardial contractile function despite a normal LV EF.更多还原