应用改良Ameroid法建立冠状动脉慢性狭窄模型的实验研究

目的：通过改良手术操作寻求一种建立高效、稳定、经济的冠状动脉慢性脉狭窄模型的方法，为康复相关基础研究提供有力模型保障。方法：实验选用普通级雄性苏中猪17头，通过改良的Ameroid法把缩窄器(Ameroid Constrictor)放置在猪的冠状动脉左回旋支主干上，制作冠状动脉左回旋支慢性狭窄模型。结果：17头猪中术后存活4周以上的12头猪大体标本显示冠状动脉左回旋支主干完全闭塞，且均无明显肉眼可见的心肌梗死。结论：通过改良的Ameroid法可以稳定地建立冠状动脉狭窄及闭塞的大动物模型。     

有氧运动训练对慢性冠状动脉狭窄后侧枝循环生成的初步研究

目的 :探讨慢性冠状动脉狭窄模型猪有氧运动训练对冠状动脉侧枝循环生成的影响。方法 :健康 3月龄猪18只 (体重 2 2 .5± 2 .0kg) ,采用Ameroid缩窄器使冠状动脉左回旋支形成慢性冠状动脉狭窄模型后 ,进行中等强度有氧运动训练 4周、6周和 8周。采用微粒体技术观察缺血心肌的局部血流改变 ,并通过病理学检查观察形态学改变。结果 :术后存活超过 4周的猪全部稳定形成冠状动脉左回旋支完全闭塞 ,但无心肌梗死。运动组冠状动脉左回旋支血管支配区心肌局部血流量和毛细血管密度较基础值显著增加 (P <0 .0 1) ,且与训练时间呈正相关 (r=0 .73 0 ,P <0 .0 1) ,同时显著高于对照组 (P <0 .0 1)。结论 :有氧运动训练有利于促进慢性冠状动脉狭窄猪的侧枝循环生成     

应用改良Ameroid法建立冠状动脉慢性狭窄模型的实验研究

目的:通过改良手术操作寻求一种建立高效、稳定、经济的冠状动脉慢性脉狭窄模型的方法,为康复相关基础研究提供有力模型保障。方法:实验选用普通级雄性苏中猪17头,通过改良的Ameroid法把缩窄器(AmeroidConstrictor)放置在猪的冠状动脉左回旋支主干上,制作冠状动脉左回旋支慢性狭窄模型。结果:17头猪中术后存活4周以上的12头猪大体标本显示冠状动脉左回旋支主干完全闭塞,且均无明显肉眼可见的心肌梗死。结论:通过改良的Ameroid法可以稳定地建立冠状动脉狭窄及闭塞的大动物模型。     

中国实验小型猪慢性心肌缺血模型的制备

目的探讨一种建立和评价慢性心肌缺血动物模型的简易方法。方法中国实验小型猪22头,开胸游离冠状动脉左回旋支主干,在左旋支近段放置Ameroid缩窄环,制作左旋支慢性闭塞的模型,术后5周行冠状动脉造影和心脏MR检查。结果22头中国实验小型猪中20头成活并成功建立慢性心肌缺血模型,应用Ameroid缩窄环后5周可见左旋支完全或次全闭塞,左旋支支配范围(左心室侧壁或下壁)心肌室壁增厚率及室壁运动幅度明显下降(P<0.01)。所有动物均示静息时和/或负荷后LCX支配范围内心肌灌注缺损。结论应用Ameroid缩窄环可以成功制作慢性心肌缺血的动物模型。     

有氧训练对猪慢性冠状动脉狭窄后内皮细胞介导的侧支循环依赖血管扩张的影响

目的探讨有氧训练后侧支循环依赖血管的扩张与内皮介导的一氧化氮合酶(ecNOS)的基因表达之间的关系. 方法健康雄性3月龄猪22只,采用Ameroid缩窄器建立慢性冠状动脉左回旋支(LCX)狭窄模型后,随机分为对照组(n=7)和运动组(n=8).对照组保持安静饲养7周;运动组进行中等强度有氧运动训练7周.以逆转录-聚合酶链反应(RT-PCR)法测定未狭窄冠状动脉左前降支(LAD)和侧支循环依赖的LCX小动脉ecNOS的mRNA表达情况. 结果运动组LCX和LAD小动脉的ecNOS mRNA的表达无差异,P>0.05;对照组LCX小动脉ecNOS的mRNA表达较LAD显著下降,P<0.01. 结论运动训练可以上调狭窄的冠状动脉ecNOS的基因表达,增加一氧化氮(NO)的产生,改善侧支循环依赖的血管的扩张,改善心肌供血.     

直接心肌内注射血管内皮生长因子基因对慢性缺血心肌侧枝循环生成的影响

目的观察血管内皮生长因子基因(rAAV2-hVEGF165)直接心肌内注射促进慢性缺血心肌侧枝循环生成的作用。方法小型猪左冠状动脉回旋支放置血管缩窄环,建立慢性心肌缺血模型。5周后应用心电图、冠脉造影和心脏核磁共振成像确认左回旋支闭塞或相应心肌的缺血。动物随机分为实验组和对照组,分别在缺血心肌内直接注射rAAV2-VEGF165(1×1012virus genomeml)或同等量的磷酸盐缓冲液或rAAV2-LACZ(1×1012virus genomeml)。治疗后6个月,冠状动脉造影了解有无侧枝循环生成。结果放置血管缩窄环后5周,所有动物均出现左回旋支完全、次全闭塞和旋支供血区域的心肌缺血。治疗后3个月,缺血心肌内可检测到LACZ和VEGF蛋白的阳性表达;治疗后6个月,VEGF组缺血心肌内毛细血管和小动脉密度均高于对照组(P<0.05);结论直接在小型猪慢性缺血心肌内注射rAAV2-VEGF165,VEGF165基因可转染入心肌组织内,并可在缺血部位显著促进侧枝循环形成。     

小型猪慢性缺血性心脏病模型的建立

目的：通过改良手术方法建立稳定、安全的小型猪慢性缺血性心脏病模型，并建立活体判断模型建成与否的观察指标。 方法：手术于2005-01／10在香港大学动物实验中心进行。取健康巴马小型猪17只，左侧开胸后应用改良法（两线平移牵引法）在小型猪左冠状动脉回旋支起始部放置Ameroid环，具体改良环节为：①用两条丝线牵住冠状动脉的左回旋支并将两线之间的左回旋支与Ameroid环的缺槽平行对齐，立即将两者同时做相反方向的运动，迅速将其套入Ameroid环内。②在给小型猪做经口行气管插管时，气管插管在过了喉头后应顺着这个弯曲向背侧方向进入气管。4周后进行活体冠状动脉造影。 结果：17只猪中有16只猪术后存活8周以上，活体冠状动脉造影显示左冠状动脉回旋支均闭塞。 结论：通过改良手术方法能建立起稳定、安全的小型猪慢性缺血性心脏病模型，用冠状造影在活体上可确定模型成功与否。     

小型猪慢性缺血性心脏病模型的建立

目的:通过改良手术方法建立稳定、安全的小型猪慢性缺血性心脏病模型,并建立活体判断模型建成与否的观察指标。方法:手术于2005-01/10在香港大学动物实验中心进行。取健康巴马小型猪17只,左侧开胸后应用改良法(两线平移牵引法)在小型猪左冠状动脉回旋支起始部放置Ameroid环,具体改良环节为:①用两条丝线牵住冠状动脉的左回旋支并将两线之间的左回旋支与Ameroid环的缺槽平行对齐,立即将两者同时做相反方向的运动,迅速将其套入Ameroid环内。②在给小型猪做经口行气管插管时,气管插管在过了喉头后应顺着这个弯曲向背侧方向进入气管。4周后进行活体冠状动脉造影。结果:17只猪中有16只猪术后存活8周以上,活体冠状动脉造影显示左冠状动脉回旋支均闭塞。结论:通过改良手术方法能建立起稳定、安全的小型猪慢性缺血性心脏病模型,用冠状造影在活体上可确定模型成功与否。     

背向散射技术与彩色室壁运动技术评价慢性冠状动脉狭窄存活心肌的实验研究

目的　研究超声背向散射及彩色室壁运动技术对猪慢性冠状动脉狭窄、侧支循环形成后存活心肌的检出价值。方法　健康小型猪 10只 ,开胸放置Ameroid缩窄器 ,分别于手术前、术后 1d、3d、1周、2周、3周、4周利用超声背向散射、彩色室壁运动技术采集胸骨旁长轴、乳头肌短轴、心尖四腔、两腔观的标准切面图像 ,术前、术后 1周、2周、3周、4周进行冠状动脉造影 ,4周处死动物行病理检查。结果　除1只猪由于技术原因被剔除外 ,其余 9只均成功地建立了慢性冠状动脉狭窄侧支循环模型 ;术后 3d时背向散射积分值 (IBS % )升高 ,背向散射积分周期变化 (CVIB % )降低 ,1周时变化最明显 ,4周时未恢复至正常 ;而术后 3d左室后壁增厚率 (ΔT % )降低 ,室壁运动积分指数 (WMSI)升高 ,1周变化最明显 ,至 4周时与术前相比仍有明显差异 (P <0 .0 5 )。结论　背向散射与彩色室壁运动技术可以检出猪慢性冠状动脉狭窄、侧支循环形成后的存活心肌。     

可控性心肌缺血动物模型的制作

目的：建立小型猪可控性心肌缺血的动物模型。方法：健康成年小型猪10只，开胸安置自制水囊缩窄器．建立钝缘支可控性缺血的动物模型。术后行缺血心电图试验、冠脉造影、微球技术检测缺血区心肌水囊加压前后CCBF以及靶血管支配区心肌HE染色观察。结果：制作成功的8其小型猪在水囊加压后均可出现明显的缺血性心电图表现．同时钝缘支下游显影延迟、稀疏．钝缘支近乎完全闭塞，水囊压力撤除后心电图迅速恢复正常，钝缘支远端灌注恢复到水囊加压前状态。水囊加压前后靶血管支配区域CCBF明娩减少（P〈0．05）。HE染色无心肌梗死表现。结论：采用该自制水囊缩窄器可以成功制作可控性心肌缺血动物模型。     

冠脉血流显像评价慢性冠脉闭塞后心肌内侧支循环状态的实验研究

目的：应用冠脉血流显像技术检测前降支慢性闭塞后其供血区心肌内冠脉血流信号的变化，探讨该技术在评价心肌内侧支循环方面的价值。方法：24只实验小型猪，在前降支(LAD)近端放置ameroid收缩环建立慢性心肌缺血模型。放环6周后做选择性左冠状动脉造影；分别在基础状态及模型形成后应用冠脉血流显像技术观察左室前壁和室间隔心肌内冠脉血流信号的分布，同时记录其血流频谱并测定峰值血流速度(Vmax)；比较心肌内冠脉血流在模型形成前后的变化并与冠脉造影结果相对照，分析侧支循环的形成。结果：14只动物成功建立模型，根据左室前壁和前间隔内有无血流信号，将动物分为A、B两组：A组6只，前降支供血区心肌内未见明显血流信号显示，冠脉造影亦未见心外膜侧支形成；B组8只，前壁和室间隔内可见不同形式的血流信号，冠脉造影有4条见心外膜侧支形成。结论：冠脉血流显像技术能直观显示冠脉闭塞后其供血区心肌内侧支循环的建立，是冠脉造影的重要补充。     

无创性检测心外膜血流变化评价冠脉侧支循环建立的实验研究

目的：应用冠脉血流显像观察前降支(LAD)近端慢性闭塞后其中远段以及后降支(PDA)血流的变化，探讨无创检测心外膜血流在评价侧支循环方面的意义。方法：24条实验小型猪，在前降支近端放置Ameroid环建立慢性心肌缺血模型。放环6周后做选择性左冠状动脉造影和心肌声学造影，观察放环处是否完全闭塞以及造影剂在左室心肌的分布情况。分别在基础状态及放环6周后，采用左心两腔切面观察前降支远段及后降支的血流信号，记录血流频谱。结果：14条动物成功建立模型。其中6条左室前壁见明显灌注缺损，冠脉血流显像未探及前降支中远段血流信号，后降支的峰值流速与基础状态无明显差异；8条前壁见不同程度造影剂充填，其中4条前降支远端可见前向性血流信号，2条前降支远端见逆向性血流信号，这8条猪的后降支峰值流速较基础时明显增快。结论：冠脉血流显像能直接检测冠脉闭塞后相关心外膜冠脉血流的改变，可作为判断侧支循环建立的重要依据。     

建立及评价适于血流储备分数CT成像模拟的小型猪慢性冠状动脉狭窄模型

目的 建立适于血流储备分数CT成像（FFR_CT）模拟研究的小型猪慢性冠状动脉狭窄模型,并评价其可靠性。方法 巴马小型猪16头,开胸于冠状动脉前降支近或中段放置Ameroid缩窄环。建模后第2周进行冠状动脉CTA监测其狭窄程度;末次冠状动脉CTA检查2日内进行冠脉造影验证狭窄程度,并测血流储备分数（FFR）。基于冠状动脉CTA图像建立计算流体力学模型,获得FFR_CT值,并与FFR值进行比较,验证模型可靠性。结果 10头小型猪成功建模,共完成CTA检查24次,图像质量均达到诊断要求。术后第2周,前降支轻微狭窄,术后第3周9头实验猪狭窄>50%,术后第4周其余1头狭窄>50%。冠状动脉CTA示狭窄程度与冠状动脉造影结果一致。FFR_CT值与实测FFR值差异无统计学意义（t=-1.13,P=0.29）。结论 应用Ameroid环置入巴马小型猪冠状动脉左前降支近段或中段,并定期采用CTA监测,可有效建立适用于基于冠状动脉CTA图像无创性血流动力学模拟研究的慢性冠状动脉狭窄模型。     

Presence of the metabolic syndrome does not impair coronary collateral vessel formation in patients with documented coronary artery disease

OBJECTIVE: The metabolic syndrome confers an increased risk for cardiovascular morbidity and mortality. The presence of coronary collaterals may have beneficial effects during myocardial ischemia and may improve cardiovascular outcome in patients with coronary artery disease. Impaired collateral formation could be one of the reasons for the increased cardiovascular risk in patients with the metabolic syndrome. The aim of the present study was to determine the influence of the metabolic syndrome and insulin resistance on the presence of coronary collaterals. RESEARCH DESIGNS AND METHODS: We conducted a cross-sectional study in 227 patients referred for elective percutaneous transluminal coronary angioplasty to the University Medical Centre Utrecht. The metabolic syndrome was diagnosed according to Adult Treatment Panel III, and homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were used to quantify insulin resistance. Coronary collaterals were graded with Rentrop's classification. Rentrop grade >/=1 indicated the presence of collaterals. Results were adjusted for age, sex, and severity of coronary artery disease. RESULTS: A total of 103 patients (45%) were diagnosed with the metabolic syndrome. There was no association between the metabolic syndrome and the presence of coronary collateral formation (odds ratio [OR] 1.2 [95% CI 0.7-2.0]). Also, the degree of insulin resistance was not related to the presence of coronary collaterals. The OR for HOMA-IR (highest versus lowest tertile) was 0.7 (0.3-1.5) and for QUICKI (lowest versus highest tertile) 0.8 (0.4-1.6). CONCLUSIONS: The metabolic syndrome and insulin resistance are not related to the presence of coronary collaterals in patients with documented coronary artery disease.     

DSE、SPECT检测家猪慢性冬眠心肌的对比研究

目的 (1)比较硝酸甘油介入^99Tc^m-甲氧基异丁基异腈(MIBI)单光子发射计算机断层心肌灌注显像(SPECT)方法与多巴酚丁胺超声负荷试验(DSE)对慢性冬眠心肌(chronic hibernating myocardium，CHM)的检出率；(2)探讨造成两种检测方法差别的根本原因。方法 6只小型中国家猪均以右冠状动脉为靶血管，经右股动脉送入自制的缩窄器，造成冠状动脉狭窄后继续喂养1个月制备成CHM的模型。处死动物前3d分别采用硝酸甘油介入的SPECT方法及DSE方法检测CHM，获取心肌样本进行光镜、电镜检查。结果 (1)病理结果除1只动物未发生心肌梗死外，其余5只均发现病变中心区局限性心肌梗死灶。正常心肌、CHM在光镜下的结构无明显差别；(2)CHM超微结构的改变依据DSE、SPECT定位共同检出的CHM在电镜下的表现为肌丝明显稀少，线粒体小而密，糖原积聚，核周空区增大。仅依据SPECT定位共同检出的CHM在电镜下的表现为肌丝轻度稀少，线粒体小而密，糖原积聚，核周空区增大；(3)DSE和SPECT对冬眠心肌的检出率分别为73．3％、72．9％。结论 依据SPECT和DSE检出的CHM在超微结构方面的改变是不同的，DSE检出的CHM超微结构改变较SPECT检出者更为典型。     

缺氧诱导因子-1α与冠心病患者侧支循环建立的相关性研究

目的 探讨冠心病患者体内单个核细胞缺氧诱导因子-1α(HIF-1α)表达水平与侧支循环建立程度的相关性. 方法 选择冠状动脉造影至少有一支血管狭窄超过70%的冠心病患者96例为冠心病组.其中42例有可见的侧支循环,54例未见侧支循环.另选冠状动脉造影正常患者50例作为对照组.免疫组化和Western blot法检测其外周血单个核细胞HIF-1α蛋白含量. 结果 免疫组化和Westem blot两种方法检测冠心病组HIF-1α表达水平均明显高于对照组(均P<0.01),冠心痛组中有侧支循环患者比无侧支循环患者HIF-1α表达更多(均P<0.01),冠状动脉侧支循环程度与HIF-1α表达水平呈正相关(r1=0.78,r2=0.84,均P<0.01). 结论 冠心病患者外周血单个核细胞HIF-1α表达水平与侧支循环形成明显相关,外周血单个核细胞HIF-1α水平的检测有利于预测冠心病患者侧支循环形成程度.     

Fate of collateral circulation after successful coronary angioplasty of total occlusion assessed by coronary angiography and myocardial contrast echocardiography.

A well-developed collateral circulation is frequently observed in patients with total coronary occlusion. However, the fate of the collateral circulation after successful percutaneous transluminal coronary angioplasty (PTCA) has not been fully characterized. The purpose of this study was to compare the efficacy of coronary angiography and myocardial contrast echocardiography (MCE) in the evaluation of the collateral circulation after PTCA and to assess the temporal changes of the collateral circulation after successful PTCA of a totally occluded artery by using these 2 diagnostic methods. The study group was comprised of 20 consecutive patients (16 male, mean age 54 years) who underwent elective PTCA for total coronary occlusion. Coronary angiography was performed before, immediately after, and 24 hours after PTCA. MCE was also performed before, immediately after, and 24 hours after PTCA, by the intracoronary injection of sonicated radiographic contrast medium. According to the angiographic findings, the collateral circulation was graded on a scale of 0 to 3 as follows: 0 = no visible filling; 1 = collateral filling of side branches; 2 = partial collateral filling of the epicardial artery; 3 = complete filling of the epicardial artery. By MCE, myocardial perfusion by the collateral circulation was assessed by scoring the contrast pattern of collateral-dependent myocardial segments as follows: 0 = none; 0.5 = patchy or epicardial; 1 = homogeneous. The left anterior descending artery was occluded in 12 patients and the right coronary artery in 8 patients. Coronary angiographic collateral grades before PTCA were grade 2 in 5 patients and grade 3 in 15. PTCA with stenting was successfully performed in all patients without significant residual stenosis. Coronary angiography showed collateral circulation disappeared after PTCA in all patients. However, residual collateral perfusion was observed in 7 patients by MCE, performed immediately after PTCA (score 1 in 3 patients; score 0.5 in 4 patients). This residual collateral perfusion could be demonstrated even 24 hours after PTCA by MCE in 3 patients (all patients were 0.5 in myocardial perfusion score). In conclusion, successful PTCA with stenting of a totally occluded coronary artery leads to a disappearance of collateral vessels by coronary angiography in most of the patients. However, although angiographically not visible, coronary collateral circulation may persist even 24 hours after successful PTCA of a totally occluded artery demonstrated by MCE.     

Elevated levels of C-reactive protein are associated with impaired coronary collateral development

BACKGROUND: In vitro studies have shown that C-reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals. MATERIALS AND METHODS: We investigated the association between hsCRP levels and the extent of coronary collaterals according to the Rentrop classification in a cohort of 185 patients who had high-grade coronary stenosis or occlusion on their angiograms. RESULTS: Mean age was 62 years and 80% were males. Subjects with a higher grade of collaterals were significantly less likely to have diabetes mellitus (OR; 0.48, 95% and CI; 0.28, 0.83) or acute coronary syndrome (OR; 0.58, 95% and CI; 0.33, 0.99), but they were more likely to have higher number of vessels with significant stenosis (OR; 1.41, 95% and CI; 1.03, 1.93) and to have received statins (OR; 1.84, 1.09, 3.13). The mean hsCRP values reduced significantly as the Rentrop grades increased (trend, P = 0.0006). After adjusting for age, gender, statin use, clinical presentation with acute coronary syndrome, diabetes mellitus and the number of vessels with significant stenosis, each 10-unit increase in hsCRP values corresponded to a 31% reduced odds of having a higher collateral score (OR; 0.69, 95% and CI; 0.53, 0.90). CONCLUSIONS: Our findings indicate that elevated hsCRP levels are associated with a significant impairment in coronary collateralization. These data suggest a previously unrecognized mechanism through which inflammation may worsen cardiovascular outcomes.     

脑动脉狭窄或闭塞后侧支循环与卒中预后的关系

目的:通过经颅多普勒超声(TCD)评估急性缺血性卒中患者颅内外血管狭窄或闭塞时的侧支循环建立情况,并探讨其与患者预后的关系。方法:通过TCD检查115例首次急性缺血性卒中患者的脑血流动力学,发现大脑中动脉狭窄或闭塞20例,颈内动脉颅外段狭窄或闭塞12例,椎动脉起始部闭塞5例。检查这37例患者侧支循环建立情况,并记录患者入院时、出院时、发病3个月(随访时)NIHSS评分和出院时、随访时mRS评分。结果:有侧支循环者出院时NIHSS评分、随访时NIHSS评分和mRS评分均较无侧支循环者低(P<0.05)。结论:对于颅内或颈部主干动脉狭窄或闭塞患者,TCD评估侧支循环建立能评估预后,有侧支循环者预后明显优于无侧支循环者。