【作者】 杨利霞；

【导师】 穆玉明；

【作者基本信息】 新疆医科大学 ， 内科， 2008， 博士

【摘要】 目的:有关声学造影剂结合腺苷负荷对心肌缺血或梗死后是否存在微循环、微循环的状况及微循环灌注储备的评价作用尚不明确。本研究包括:1)探讨声学造影剂(MCE)对心肌缺血面积的估测作用;2)心肌声学造影(MCE)检测基础状态下不同程度的血流TIMI分级冠状动脉所供应心肌组织微循环灌注状况,评价PCI术后心肌微血管灌注的改善情况,探究其临床应用价值;3)探讨心肌声学造影(MCE)结合腺苷评价心肌微血管血流储备的可行性及临床应用价值。方法:1)本课题第一部分选择健康杂种犬12只,建立开胸犬急性心肌缺血动物模型,左前降支(LAD)结扎10min后,经静脉注射声诺维并进行MCE检查。在左室心尖长轴二腔心切面,应用MCE的彩色M型曲线技术检测急性缺血心肌分别在前壁和下壁的临界点,以此为界在二维图像上描计出声学造影剂灌注缺损面积。启动Q-analysis软件,在左室心尖长轴二腔心切面,将取样点置于对应TTC染色心肌缺血区、TTC病理染色范围大于MCE灌注缺损范围的缺血面积区域(临界区)、正常心肌组织区,动态追踪此感兴趣区,使其在造影剂再充盈的各心动周期内的每一帧图像上保持几乎相同的解剖位置,调节图像以使感兴趣区位于心肌内并容纳尽可能多的心肌,选择每一心动周期舒张末期图像纳入分析,软件自动生成灌注强度曲线并拟合函数:Y=A(1-eβ2t)+C,得出曲线峰值强度(A),曲线斜率(β)和灌注量(A·β),每个区域的参数均取3次测量的平均值。通过计算局部组织蓄积的最大微泡数量(A)和造影剂在局部充填的速度(β)测定心肌相对血流量,并作为心肌血流灌注定量判断标准。2)本课题的第二部分选择30例AMI患者及11例急性冠脉综合症患者,其中36例行PCI手术,于PCI手术前后分别进行MCE检查,将左室壁分为16节段进行心肌灌注记分,应用Qlab软件定量分析实时声学造影再灌注曲线。根据冠脉造影的结果,按冠脉血流TIMI分4级,将其所供应的心肌节段分为4组,分别进行组间MCE半定量视觉评分与定量参数值的比较,并与冠脉的血流TIMI分级程度进行相关分析。对比研究PCI手术前后各参数值的变化;3)本课题第三部分选择30例AMI及11例急性冠脉综合症患者,其中36例行PCI手术,应用实时心肌声学造影和腺苷负荷超声心动图,定量评价冠状动脉介入治疗前后心肌微血管血流储备。应用Qlab软件定量分析实时声学造影再灌注曲线,分析PCI手术前后冠脉血流储备量的变化,对PCI手术前后心肌微循环的状况和预后进行估测。结果:1)MCE所测定的左室心肌缺血面积与美蓝染色后缺血面积实际参数高度一致(r=0.93,P=0.01);与TTC染色后缺血面积实际参数一致性较好(r=0.68,P<0.01)。左室心尖长轴二腔心切面, TTC病理染色缺血心肌范围大于MCE灌注缺损范围约12.35±2.16mm。以TTC病理染色为金标准,回顾分析各个感兴趣点的定量指标,心肌正常灌注区的峰值强度(A)、曲线斜率(β)和灌注量(A·β)显著高于缺血区,缺血心肌区域声学造影的峰值强度(A)较正常心肌区明显延长,而显影持续时间却显著缩短,灌注量(A·β)较正常心肌区约降低约70%,与心肌正常灌注区之间差异有统计学意义(P<0.05)。TTC病理染色缺血心肌大于MCE灌注缺损的面积区域声学造影的峰值强度(A)较正常心肌区延长,而显影持续时间亦缩短,灌注量(A·β)较正常心肌区约降低约50%,与心肌正常灌注区之间差异有统计学意义(P<0.05)。2)41例患者术前均顺利完成MCE检查,36例患者PCI术后顺利完成MCE复查。MCE检出心肌灌注异常与相应供血支冠状动脉血流TIMI≤2级的符合率为79%(193/244)。当心肌灌注MCE记分为0时,MCE检出心肌灌注异常与相应供血支冠状动脉血流TIMI<1级的符合率为70%(40/57)。而MCE记分为1时,MCE检出心肌灌注异常与相应供血支冠状动脉血流TIMI>2级的符合率为73%(272/374)。MCE半定量分析显示冠状动脉血流TIMI分级程度不同,MCE分值差异有显著性(P<0.05)。PCI手术前病变血管相应心肌节段的A、β、A·β明显低于正常灌注节段(P<0.001),4组间的A、β及A·β均存在明显差别(F=103.36,91.13,87.34,P<0.01),做任意两组间的t检验,其A、β及A·β差异均有统计学意义(P<0.05)。随冠脉血流TIMI分级的降低,其心肌微循环灌注参数(A、β、A·β)指标降低越明显,而各组内A、β、A·β与冠脉血流TIMI分级的程度并无明显相关性(P均>0.05)。视觉记分在PCI前后存在明显差异(P<0.05),提示PCI治疗后局部心肌灌注区视觉显影较术前有明显改善。择期PCI治疗后梗死节段的A、β、A·β值仍低于正常节段(P<0.05),标化后Ar、βr、及A·βr三个参数值在PCI后均有显著改善(P<0.01);PCI术前视觉评分为0-0.5分者,标化后Ar、βr、及A·βr三个参数值在PCI后均有显著改善(P<0.05);术前视觉评分为1分者,Ar、βr、及A·βr术后有改善,但其变化差异无统计学意义;随着术前血流TIMI分级程度的降低,PCI术后Ar、βr、及A·βr三个参数值增加越少,结果显示术前病变血管的微循环灌注的损害程度直接影响其血流储备量。3)41例患者术前均顺利完成MCE结合腺苷负荷检查,36例患者PCI术后顺利完成MCE结合腺苷负荷的复查。PCI术前的静息状态下,A、β和A·β值随着供血冠脉血流TIMI分级程度的降低而降低(P<0.01);在腺苷负荷状态下,A、β和A·β值亦随着供血冠脉血流TIMI分级的降低而降低(P<0.01),且其储备值呈现出相同的趋势(P<0.01)。PCI术后静息与负荷状态下,β和A·β值亦呈现此趋势,其血流储备量较PCI术前明显增加,但心肌节段A、β、A·β储备值仍低于正常灌注组(P<0.05)。随着术前血流TIMI分级程度的降低,PCI术后A、β、A·β储备值增加减少,结果显示术前病变血管的微循环灌注的损害程度直接影响其血流储备量。结论:1)心肌声学造影MCE可用于心肌缺血面积的估测,测定心肌缺血范围,但在急性夹闭冠状动脉制造犬急性缺血模型的情况下,存在低估急性缺血范围的可能性,因此测定MCE灌注缺损区范围外12.35±2.16mm面积内的A·β心肌血流量可以提高缺血面积的界定。2)MCE视觉记分与血流量定量分析显示冠状动脉血流TIMI分级程度越低,MCE视觉评分及定量微循环血流量值越低,MCE能客观地反映冠状动脉血流TIMI分级的程度。PCI术后,血流TIMI分级在评价冠状动脉微循环灌注的改善与否有局限性,而MCE对术后疗效的评价具有补充及指导意义。3)PCI术前血流储备越差,术后冠脉血流储备改善越差。心肌声学造影结合腺苷负荷试验定量测定心肌血流储备,可以预测患者愈后,有助于介入性治疗前病人的筛选、术后疗效评价。更多还原

【Abstract】 Objective: Previous studies ST-MCE was safe and feasible for assessing perfusion in Myocardial microcirculation.However, little was known about differention and the role about the Adenosine Stressing Myocardial Contrast Echocardiography.As a result, the present study aimed at resolving several issues including: 1) To assess ischemic myocardium area by Myocardial contrast echocardiography(MCE). 2) To investigate the diagnostic value of myocardial contrast echocardiography (MCE) and the grade of TIMI in evaluating myocardial microcirculation perfusion and clinical applications.To assess resting myocardial perfusion by MCE in patients with coronary artery disease before and after PCI surgery. 3) To investigate the diagnostic value of adenosine stress myocardial contrast echocardiograph in assessing reserve of myocardial microcirculation before and after PCI surgery ,and to establishing the feasibility and clinical applications. Methods: 1) Eleven Open chest dogs were performed by in travenous MCE after ten minutes of left anterior descending coronary artery (LAD) occlusion for acute ischemia.M-mode of MCE defined the cut-off value of ischemic myocardium, and marked in anterior and inferior in 2D images, respectively. Ischemic area was curved and compared with pathologic result.Accoding TTC results ,put the aim on normal ?ischemic and suspicious area and analyzed quantitatively from microbubble replenishment curves for myocardial perfusion. 2) Thirty AMI and eleven ACS patients were examined by MCE using Sonovue intravenous injection before selective coronary angiograph.Thirty-six of patients were examined by MCE again after PCI surgery. The images of MCE were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion .Left ventricular myocardial segments,divided into 4 groups according to the grade of TIMI of coronary artery detected by coronary artery angiography. Acoustic density parameters were compared among these groups, and the correlation between these parameters and the grade of TIMI of coronary artery .3) Thirty AMI and eleven ACS patients were examined by MCE at baseline and after adenosine stress administration before selective coronary angiograph.Thirty-six patients referred for PCI surgery . After and before PCI the patients were referred subsequent revascularization underwent MCE at baseline and after adenosine stress administration. The images of MCE were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion and its reserve. Results: 1) There was correlation between Meis blue dye area and MCE ischemic area (r=0.93, P=0.01). There was correlation between TTC staining area and MCE ischemic area (r=0.68, P=0.01). Accoding TTC results ,the ischemic area in TTC is larger about 12.35±2.16mm than the ischemic area in MCE. The images of MCE were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion. The A?βand A·βin the ischemic and suspicious area were significantly different versus the normal area. 2) Results among the 4 groups were significantly respectively (P<0.05), the A ?βand A·βwere decreased significantly with the grade of TIMI of coronary artery (all P<0.05); Before PCI surgery, A?β?and A·βwere significantly lower in the regions of interest with severe lower the grade of TIMI of coronary artery than those with normal coronary artery (P<0.05). the normalized value of Ar?βr?and A·βr were higher after PCI surgery than those before operation (P<0.05). 3) At baseline, significant differences in A ?βand A?βparameter were observed among groups of graded TIMI severity groups. Under adenosine stress,significant differences in A,βand A·βvalue could be observed among groups which showed that the lower the grade of TIMI severity, the lower the MCE parameters. Graded decreasing in the reserves of A,βand A·βcould also be observed with decreasing coronary the grade of TIMI severity. Furthermore, Some significant differences inβ, A·βcould be observed between segments with CBF and those without. Conclusion: 1) MCE is applicable to assess ischemic myocardium area. But defining myocardial infarct size by MCE ischemic area maybe lowly diagnose ischemia size,so we can improve by the A?βand A·βfrom microbubble replenishment curves for myocardial perfusion in 12.35±2.16mm out of the ischemic area in MCE. 2) Perfusion abnormalities are present in patients with severe lower the grade of TIMI of coronary artery and can be detected by MCE. However, myocardial microcirculation perfusion does not correlate with the grade of TIMI of coronary artery completely. further more, MCE can provide valuable information on t he outcome of coronary artery PCI surgery in these patients. 3) Quantitative MCE in conjunction with adenosine stress is feasible to identify and selsction AMI for PCI as well assesses the contribution of perfusion in myocardial microcirculation before or after PCI surgery.更多还原