心肌超声造影安全性的实验研究

摘要

目的 综合运用超声及病理技术评价心肌超声造影对犬心肌局部病理损伤及力学状态的影响.方法 11只开胸比格犬动物模型,采集基础状态及仅超声辐照5min(发射频率1.7/3.4 MHz,机械指数1.0)后左心室短轴观二尖瓣水平、乳头肌水平及心尖水平3个完整心动周期二维动态灰阶图像.再经股静脉团注声诺维5 ml并予以超声辐照5 min,并于辐照后即刻、20 min、40 min、60 min各时间点分别采集前述图像.Echo PAC多参数工作站分析计算3个短轴观各节段周向应变及应变率、径向应变及应变率,同时计算常规心功能参数.取犬离体心脏行局部心肌HE染色光镜及透射电镜检查.结果 ①常规心功能参数比较,造影前后各状态犬心率、血压、射血分数、左室收缩末容积及舒张末容积、每搏量、心输出量、二尖瓣口前向血流流速曲线E/A、组织多普勒二尖瓣环e/a、E/e等指标差异均无统计学意义(P＞0.05),实验全过程中犬生命体征平稳.②基础状态各节段周向应变及应变率、径向应变及应变率与仅超声辐照对照组及造影后各时间点比较,多数节段各参数较基础状态有一增大趋势,但差异无统计学意义(P＞0.05).③病理切片HE染色光镜下见近外膜处心肌细胞少量炎症细胞浸润(检出率21.2％),心肌纤维断裂溶解(检出率6.1％).④透射电镜检查见线粒体在肌丝间排列规整、嵴膜清楚、质膜完整,未见肌浆网扩张;可见局部内皮细胞轻度肿胀(检出率28.6％),红细胞漏出(检出率42.9％),肌丝局限性溶解(检出率21.4％),面积不足整个视野的10％；未见心肌膜破坏与闰盘分离；核染色质无明显边聚.结论 心肌超声造影对犬心脏整体功能及局部力学状态无显著影响,未造成严重病理损伤.%Objective To evaluate the myocardium damage of myocardial contrast echocardiography (MCE) and the impact on regional left ventricular mechanics by imaging and pathology techniques.Methods Eleven open-chest animal models of Beagle were employed to collect the short-axis views of mitral annular,papillary muscle and apical level of three complete cardiac cycles using gray-scale imaging at the baseline and blank irradiation 5 min later(transmitting frequency 1.7/3.4 M Hz,mechanical index 1.0).After that,5 ml of SonoVue was gotten a shot by intravenous bolus injection,the heart was exposed by ultrasonic wave for 5 min continuously,and then the same images collected were at the point-in-time irradiation immediately,20 min,40 min and 60 min later.The short-axis circumferential strain and strain rate,radial strain and strain rate were measured and calculated by EchoPAC multi-parameter workstation,meanwhile including conventional of cardiac function.All the dogs were killed after the experiments and the myocardium was harvested for HE staining and observed with transmission electron microscope for the tissue microstructure.Results ①Conventional parameters of cardiac function:there was no significant difference before and after MCE in the heart rate,blood pressure,ejection fraction,left ventricular end-systolic volume and end-diastolic volume,stroke volume,cardiac output,mitral flow spectrum prior to the E/A,tissue Doppler mitral annular e/a and E/e ( P ＞0.05).During the whole process of experiment,the dogs’ vital signs were stable.②Compared the segmental circumferential strain and strain rate,radial strain and strain rate between baseline and each treatment groups,these parameters had a trend of increase in most segments,but the difference was not statistically significant in most segments (P ＞0.05).③HE staining at the light microscope demonstrated a small amount of myocardial cell infiltration of inflammatory cells near the outer membrane (21.2％),and very few part of the muscle fibers dissolved and fractured (6.1％).④The section of transmission electron microscope showed all the structures were normal except that a small amount of endothelial cells were mild swelling,some red blood cells were leaked,some myofilaments were regional dissolved,the relevance ratio were 28.6 ％,42.9 ％ and 21.4 ％ respectively,and the abnormal area was less than 10％ of the entire field of vision.Conclusions MCE has no significant impact for the global function of heart and the regional mechanical state,and furthermore there is no serious pathological damage on the myocardium.