【作者】 杨永宾；

【导师】 冯光兴；

【作者基本信息】 河北医科大学 ， 外科学， 2010， 硕士

【摘要】 目的:缺血性二尖瓣反流(IMR)是继发于心肌缺血尤其是急性心肌梗死(AMI)的功能性二尖瓣反流。急性心肌梗死早期,缺血性二尖瓣反流发生率约为17～55%,而约有15%在心梗后数月内仍可发生。发生任何程度二尖瓣反流的心梗患者,其心血管死亡率明显高于无反流者。缺血性二尖瓣反流发生机制复杂,不同梗死部位其发生机制也不尽相同,本实验通过对山羊的冠状动脉-左心室联合铸型,了解后乳头肌动脉供应情况,探索出通过山羊下壁心梗来建立缺血性二尖瓣反流模型的方法。并在建立山羊急性缺血性二尖瓣反流动物模型后,开放血管,观察心梗早期血流再灌注对缺血性二尖瓣反流的治疗作用。方法:1山羊后乳头肌及其附着室壁动脉供应研究选取新鲜、完整的羊心20只,用肝素水将冠状动脉及左室腔内的血凝块冲洗干净,ABS树脂和丙酮以1:20的比例配制成灌注液,加压灌注左右冠状动脉及左室腔,浸入水中凝固,4小时后向左室腔补注铸型剂,凝固12小时后置入37%盐酸溶液腐蚀,48小时后取出标本,流水冲洗,去除残余心肌组织。2山羊缺血性二尖瓣反流模型建立及再灌注治疗本地奶山羊11只,体重15～20kg,随机分为对照组(n=3)和实验组(n=8)。所有山羊术前在麻醉状态下进行心超检查,从左室短轴、左室长轴及胸骨旁四腔三个切面进行扫描,记录二尖瓣反流情况、左室腔大小及左室功能等数据。以3%戊巴比妥钠30mg/kg静脉麻醉,气管插管接呼吸机辅助呼吸,左则第四肋间开胸,开胸后给予肝素钠注射液1mg/kg。切开心包暴露左冠状动脉回旋支及其分支,在左室后侧壁、房室沟下方2cm处选择表浅动脉作为阻断点,动脉下方置线,对照组仅置线不结扎,实验组结扎冠脉。实验过程中监测心电图,对照组心电图无变化,实验组心电图II、III、AVF导连出现ST段抬高。确定模型建立成功后膨肺关胸,6小时后再次超声检查,扫描方法及项目同术前。超声检查后二次开胸,剪断结扎线,冠脉复流。72小时后超声检查,项目同前。所有山羊均在术前、术后6h、12h、24h、72h静脉采血2ml,1000转/分离心10分钟,提取上清液,存放于-80℃冰箱保存备用。固相夹心法酶联免疫吸附实验(ELISA)测定血浆中CK-MB的含量。处死山羊后在心脏梗死区、非梗死区及前、后乳头肌取组织块,置于5%福尔马林溶液中固定,制作HE染色病理切片。结果:1冠状动脉-左心室联合铸型显示山羊后组乳头肌由回旋支的第二、三分支单独或共同供应,此两分支在进入乳头肌前在心表的位置均位于左室后侧壁、房室沟下方2cm处。(Fig.1)2两组山羊均无死亡。实验组8只山羊缺血性二尖瓣反流发生率为100%,对照组均无反流发生。实验组术后六小时心超结果中,山羊左室舒张末内径、左室球形度、左室射血分数、二尖瓣瓣环直径与术前相比无统计学意义(P>0.05)。左室收缩末内径、前后乳头肌间距、后乳头肌-前瓣环距离均比术前增大,具有统计学意义(P<0.05),后乳头肌收缩值、后乳头肌附着室壁运动指数较术前减小,具有统计学意义(P<0.05)。对照组各项数据变化均无统计学意义(P>0.05)。实验组梗死区再灌注后,二尖瓣反流程度减轻,有统计学意义(P<0.05)。乳头肌间距、后乳头肌-前瓣环距离、后乳头肌收缩值、左室收缩末内径与梗死后6小时相比变化均有统计学意义(P<0.05)。与术前相比二尖瓣反流仍然存在,有统计学意义(P<0.05)。乳头肌间距、后乳头肌-前瓣环距离术前相比仍然增大,有统计学意义(P<0.05)。后乳头肌收缩值比术前减小,有统计学意义(P<0.05)。结论:1山羊冠状动脉位置表浅,回旋支粗大,其供应后乳头肌的分支在心表位置相对固定,易于定位。2下壁心肌梗死后缺血性二尖瓣反流发生率较高。梗死累及后乳头肌及其附着室壁,导致收缩期左室内径扩大、后乳头肌移位及局部室壁运动障碍是急性缺血性二尖瓣反流的主要致病因素。3缺血区再灌注后二尖瓣反流减轻,说明早期冠脉血运重建对于缺血性二尖瓣反流具有治疗意义,其治疗作用是通过改善局部室壁运动功能,减轻乳头肌移位实现的。4由于冠状动脉梗阻已造成部分左室壁及后乳头肌梗死,冠脉血运重建不能逆转梗死病变,因此不能彻底治疗缺血性二尖瓣反流。更多还原

【Abstract】 Objectives: Ischemic mitral regurgitation (IMR) is a common complication of acute myocardial infarction (AMI), which is recognized as functional regurgitation. Acute IMR is present in 17% to 55% of patients with AMI, and chronic IMR will occurs in approximately 15% of patients without acute IMR several months later. Even the presence of mild MR is a powerful independent predictor of reduced survival after AMI.The pathophysiology of IMR is complex, and its mechanism is various in different location of infarction. In this study, we explored a approach of inferior myocardial infarction model in goat, by learning about the coronary artery and left ventricular cavity casting. Infarct-related artery was reperfused after the animal models established, and therapeutic effect of reperfusion therapy was observed.Methods: 1 The study of arterial supply of posterior papillary muscle and adjacent ventricular wall in goat heartSelecting 20 goat hearts, blood clot in coronary artery and left ventricular cavity were rinsed with heparin solution. Perfusate was made with ABS resin and Acetone at the proportion of 1:20, which was injected into the coronary arteries and left ventricular cavity. And then put the goat heart into the 37% hydrochloric acid solution. 48 hours later, the residual myocardium was removed with running water, and researching the castings.2 The establishment of acute IMR model in goat and reperfusion therapyEleven local goats between 15 and 20kg were randomly divided into control group (n=3) and experimental group (n=8). All goats were detected by Doppler Echocardiography before operation. Mitral regurgitation, left ventricular cavity size, left ventricular function and other data were measured. Total goats were anesthetized with sodium pentobarbital (30mg/kg IV), intubated and ventilated. A surface ECG was monitored and a sterile left thoracotomy performed. Heparin sodium were injected with dose of 1mg/kg after thoracotomy in order to prevent thrombosis after blocking coronary artery. In experimental group, the second or third obtuse marginal branches of the left circumflex coronary artery(2cm below the atrioventricular groove) was ligated. In control group, the suture was put in the same position but wasn’t ligated. The electrocardiogram of control group had no change. The S-T segment of II, III, AVF lead rose in experimental group. The incision was closed, and echo images were repeated after 6 hours, scanning methods were the same as preoperation.A second thoracotomy was performed after Echocardiography. The ligature was cut and the infarct-related artery reflowed. Echocardiographic data were collected again after 72 hours. Taking 2ml venous blood before operation, 6h, 12h, 24h and 72h after operation in every goats. And centrifuged them by 1000 roll/minute for 10 minutes, extracting the supernatant stored in -80℃refrigerator. ELISA was used to measure content of CK-MB in blood serum. Tissues were taked in infarct zone and papillary muscles after goats were sacrificed. These tissues were placed in 5% formalin solution for making pathological sectionResults: 1 By studying the coronary-ventricular castings, we found that the artery supply to posterior papillary muscle and adjacent ventricular wall comes from the second or third obtuse marginal branches of the left circumflex coronary artery.These branches locate approximately at the same position before them entering the myocardium: inferior-lateral wall and 2cm below the atrioventricular groove. (Fig.1)2 There was no death in two groups. The incidence of ischemic mitral regurgitation was 100% in experimental group. The control group had no regurgitation occurred. In experimental group, the echocardiographic data of 6h after operation shows EDD, EF, Left ventricular sphericity and Mitral Annular diameter did not change significantly compared with those preoperative(p>0.05). ESD, APM-PPM, PPM-AMA were obviously higher than those preoperative, there was statistical significance (p<0.05).PPM contracted values and WMI were decreased significantly in data of 6h after operation (p<0.05).The differences of echocardiographic data before and after operation in control group were not significant (p>0.05).MR was obviously reduced after reperfusion in experimental group. The differences were statistical significance (p<0.05). ESD, APM-PPM, PPM-AMA were obviously lower than those in 6h after infarction (p<0.05). PPM contracted values increased,there were statistical significance (p<0.05). Mitral regurgitation were still exists compared with preoperation, there were statistical significance (p<0.05). APM-PPM, PPM-AMA were still larger than preoperation, there were statistical significance (p<0.05).The PPM Contracted values significantly decreased compared with preoperation(p<0.05).Conclusions: 1 The left circumflex of goat coronary artery is bulky and superficial. The branches supply to posterior papillary muscles is relatively fixed under epicardium, and easily to be located.2 The incidence of IMR is higher in inferior myocardial infarction. Infarction involving the posterior papillary muscle and adjacent left ventricular wall result in displacement of papillary muscles and segmental post-wall movement disorders and left ventricular dilatation at the End of systole, which are the major determinants of IMR .3 IMR decreased after reperfusion, indicating that early coronary revascularization has a therapeutic effect for ischemic mitral regurgitation. That is because of the improvement of regional wall motion function and mitigation of the displacement of papillary muscles.4 Part of posterior papillary muscle and adjacent left ventricular wall were necrosis after the coronary artery obstruction, so coronary artery revascularization could not reverse infarct lesions and could not cure IMR.更多还原