【作者】 王曼；

【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， 2007， 硕士

【摘要】 急性心肌梗死(Acute Myocardial Infarction,AMI)是临床常见的的心血管疾病,其发病率占心血管疾病首位,随着医学技术的发展,AMI病死率有所下降,但存活者病情仍可出现复发或难治性心功能不全等并发症,有资料显示,AMI合并心力衰竭病死率可高达80%。因此,对AMI左室整体及局部心肌收缩功能的评价可准确判断缺血心肌的功能状态,早期确诊缺血性心脏病,并能估测疾病的预后,在诊断和指导临床治疗上具有重要意义。超声定量组织速度成像(Quantitative Tissue Velocity Imaging ,QTVI)技术可在心动周期中同时显示不同心肌节段运动的速度曲线,可同步获得多至8个取样部位的心肌节段在各时相的运动情况,为无创性定量评价局部心肌运动功能提供了一种新方法。多聚ADP核糖聚合酶[poly(ADP-ribose) polymerase,PARP]广泛存在于真核细胞内,活化的PARP参与DNA修复过程。细胞缺血缺氧可导致DNA损伤,而大量DNA损伤,PARP过度激活,可导致ATP耗竭,细胞因功能障碍而死亡。3-氨基苯甲酰胺(3-Aminobenzamide, 3-AB)可抑制PARP活性,降低DNA修复过程中细胞内ATP的消耗,已用于多器官组织细胞缺血损伤的治疗研究,对缺血心肌的治疗具有潜在价值。目前大鼠心肌梗死模型是一种成熟的心梗动物模型,常用于缺血性心脏病的各种病理生理过程与临床相关疗效评价的基础研究。本研究旨在应用QTVI技术评价急性心肌梗死大鼠左室局部收缩功能的变化,亦应用多聚ADP核糖聚合酶抑制剂3-AB对急性心梗大鼠左室收缩功能进行干预,以期探讨QTVI技术评价急性心梗大鼠局部心肌功能的可行性和准确性,评价3-AB干预对梗死心肌的作用,为3-AB治疗心肌梗死的有效性提供实验依据。研究分两部分:第一部分定量组织速度成像技术评价急性心肌梗死大鼠左室局部收缩功能的实验研究应用超声定量组织速度成像技术(QTVI)评价急性心肌梗死模型大鼠左室形态及收缩功能的变化。雌性Wistar大鼠12只,结扎冠状动脉左前降支成功建立心梗模型。另设假手术组10只。术前及术后1周所有大鼠均采用超声心动图检查,检查完毕后处死取心脏,测量左室舒张末期内径(LVEDD)及舒张末期容积(EDV)。结果显示:与假手术组相比,心梗组的左室前壁舒张末期厚度(LVAWd)明显变薄(P<0.01),收缩末期内径(LVESD)显著增加(P<0.01);左室短轴缩短率(FS)、射血分数(LVEF)、球形指数(SI)显著降低(P<0.01);短轴方向上前间隔及长轴方向上左室侧壁各节段定量组织速度成像收缩期峰值速度显著下降(P<0.01)。二尖瓣环收缩期平均峰值速度与左室射血分数、球形指数成线性相关(r分别为0.88、0.79,P<0.01)。超声测定LVEDD与EDV与实测值具有高度一致性。第二部分定量组织速度成像技术评价3-AB干预对急性心肌梗死大鼠左室收缩功能的实验研究本研究应用定量组织速度成像技术(QTVI)评价3-氨基苯甲酰胺(3-AB)对大鼠急性心肌梗死后左室收缩功能的影响。将冠状动脉左前降支起始部结扎的雌性Wistar大鼠分为3-AB干预组(n=14)和空白对照组(n=10)。分别用3-AB及生理盐水干预2周后行超声心动图检查。结果显示:与3-AB组相比,对照组的左室前壁舒张末期厚度(LVAWd)明显变薄(P<0.05),左室舒张末期内径(LVEDD)、舒张末期容积(EDV)显著增加(P<0.05);左室短轴缩短率(FS)、射血分数(LVEF)显著降低(P<0.05);短轴方向上前间隔及长轴方向上左室侧壁心肌各节段定量组织速度成像收缩期峰值速度显著下降(P<0.05)。二尖瓣环收缩期平均峰值速度与前间隔收缩期峰值速度均与心肌病理积分成线性相关(r分别为-0.92、-0.78,P<0.001)。超声测定计算左室质量(LVM)与实测值具有良好相关性(r=0.93, P<0.01)。结论:在本实验条件下,本研究得出以下结论:1、QTVI技术结合二维超声心动图可以较全面、定量、无创评价急性心肌梗死大鼠整体和局部收缩功能。2、3-AB能够明显缩小急性心肌梗死大鼠模型的左室扩张程度,改善左室整体及局部收缩功能。更多还原

【Abstract】 BACKGROUND AND PURPOSE Acute Myocardial Infarction(AMI) is an important cardiovascular disease with high mortality and morbidity clinically.The morbility of AMI is the top1 reason account for cardiovascular disease.Survivor of the AMI may recurrence or come with serious complication such as heart failure.The mortality of AMI combined with heart failure may reach 80%.Studying on the myocardial function and its left ventricular(LV) global and regional function dynamic changing during ischemia is essential to diagnose coronary artery disease accurately in early stage and assess the prognosis of patients.Quantitative Tissue Velocity Imaging (QTVI) is one of the echocardiographic technique of Tissue Doppler Imaging, it can apply different myocardial segments velocity trace in the whole cardiac cycle synchronously.It is a promising measuring that can acquire the velocity data of myocardial segments non-invasive and quantitatively.Poly(ADP-ribose) polymerase(PARP) is a nuclear enzyme present in eukaryotes, functions as a DNA damage sensor and a signal transduction molecular,has been implicated in DNA repair and maintenance of genomic integrity.Cellular ischemia and anoxia causes DNA damage,then PARP activation.Severe DNA damage leads to overactivation of PARP,resulting ATP depletion and necrotic cell death. PARP inhibitors,such as 3-Aminobenzamide(3-AB), can depress the ATP consuming during DNA repairing, may prove useful for the therapy of multiple organ ischemic diseases,as has been shown in preclinical animal models.At present,the model of myocardial infarction in rats is a ripe animal model that used for the basic study of pathophysiology and the evaluation of drug effect on ischemic heart disease. In this study,we analyzed the QTVI patterns and regional myocardial velocity trace in myocardial infarction rats model,PARP inhibitor 3-AB was used during ischemia process,and its potential myocardial protective functions against ischemia injury was evaluated by QTVI.The aims are to establish the feasibility of QTVI evaluation in myocardial infarction rats model,and assessing the drug effect.at the same time,to provide experiment evidence of 3-AB as therapeutic candidates for the management of myocardial ischemia injury.This thesis is composed of two parts:PART 1. Experimental study of evaluation on left ventricular regional function by quantitative tissue velocity imaging after myocardial infarction in ratsTo investigate the value of QTVI in evaluating LV morphological and function changes in rats before and post myocardial infarction. Myocardial infarction group, female Wistar rats(n=12), ligation of the main branch of left coronary artery; sham-operated group (n=10),before and 1 week after the operation, echocardiaogra -phy scan was performed in each group. All the rats are sacrificed to measure the LV end-diastolic diamete(rLVEDD)and LV end-diastolic volume(EDV).Results Compared with sham-operated group, the LV end-systolic diameter(LVESD)in the myocardial infarction group were significantly increased (P<0.01), The LV anterior wall end-diastolic diameter(LVAWd), the parameters of LV systolic function(FS),ejection fraction(EF) and sphericity index(SI) were all significantly decreased (P<0.01). The peak radial velocity at the segment of anterior interventricular septum significantly decreased (P<0.01).The peak systolic longitudinal velocity at mitral annulus and segments of left ventricular lateral wall in infarcted group were also significantly decreased (P<0.01).The mean peak systolic velocity at mitral annulus correlated positively to left ventricular ejection fraction and sphericity index(r=0.88、0.79,P<0.01).The LV end-diastolic diameter(LVEDD) and LV end-diastolic volume (EDV)measured by ultrasound and those measured by autopsy both match well. PART 2. Experimental study of evaluation of the effects of 3-Aminobenzamide on left ventricular systolic function after acute myocardial infarction in rats by quantitative tissue velocity imagingTo assess the effects of 3-Aminobenzamide(3-AB) on LV systolic function after acute myocardial infarction in rats by quantitative tissue velocity imaging and two-dimensional echocardiography.After ligation of the main branch of left coronary artery,24 female Wistar rats were finally assigned to two groups:3-AB group (n=14), acute myocardial infarction control group (n=10).Two weeks after treatment with 3-AB, echocardiography was performed in each group.The heart was to dissected weigh the leftventricle in the scales.Results Compared with 3-AB group, the LV end-diastolic diameter(LVEDD)and LV end-diastolic volume(EDV) in the control group were significantly increased (P<0.05), The LV anterior wall end-diastolic diameter(LVAWd), the parameters of LV systolic function(FS) and ejection fraction(EF) were all significantly decreased (P<0.05). The peak radial velocity at the segment of anterior interventricular septum significantly decreased (P<0.05).The peak systolic longitudinal velocity at mitral annulus and segments of left ventricular lateral wall in infarcted group were also significantly decreased (P<0.05). The mean peak systolic velocity at mitral annulus and the peak radial velocity at the segment of anterior interventricular septum both are correlated negtively to pathologic scores(r=-0.92、-0.78,P<0.001).Left vetricular weight measured by ultrasound and those measured by autopsy match well. CONCLUSIONS:Under the conditions of the present experiments,our conclusions are:1. Using quantitative tissue velocity imaging combined with two-dimensional echocardiography, we can assess LV global and regional systolic function after myocardial infarction rats comprehendsively, quantitatively and noninvasively.2. 3-AB has beneficial effects on preventing LV remodeling and improving LV global and regional systolic function after acute myocardial infarction in rats.更多还原