冠状动脉微循环及微血管性心绞痛的研究进展

冠状动脉微循环在心肌的血供中起着重要作用。心肌声学造影是诊断微循环水平心肌灌注的新技术,可同时观察心脏的结构、心肌局部和整体功能以及心肌的各级血流灌注,有利于研究冠状动脉微循环的病理生理机制并可能检出早期微血管内皮功能不全。在正常健康人,肌源性血流依赖性微动脉扩张和微循环代谢产物导致的冠状动脉微循环收缩形成互相制约的平衡调节机制,保持正常血流灌注。在冠心病心肌缺血如劳力性心绞痛时由于心肌代谢增加氧耗增加导致心肌缺血时,微血管反而收缩加剧缺血。研究表明这类患者是由于小冠状动脉扩张储备减低或冠状动脉收缩而导致心肌缺血,冠状前小动脉是调节心肌血液灌注的主要功能部位。     

直接心肌内注射碱性成纤维细胞生长因子基因改善慢性缺血心肌收缩功能的实验研究

目的观察直接心肌内注射碱性成纤维细胞生长因子(bFGF)基因对慢性缺血心肌收缩功能的改善作用。方法将10只猪的慢性心肌缺血模型,随机分为bFGF基因治疗组(A组,6只)和对照组(B组,4只)。超声心动图(UCG)和MRI检测左心室射血分数(LVEF)和室壁增厚率(WT),评价左心室收缩功能。治疗后6周,目标区心肌标本进行心肌微血管计数。结果bFGF基因治疗后6周,UCG测得A组LVEF和WT均较治疗前提高(P<0.05),WT提高到正常值水平;A组WT值高于B组(P<0.05)。MRI测得A组LVEF和WT均较治疗前提高(P<0.05),并且达到正常值水平;A组LVEF和WT均高于B组(P<0.05)。A组心肌微血管计数多于B组(P=0.031)。结论直接心肌内注射bFGF基因可以促进心肌细小血管新生,改善慢性缺血心肌局部和左心室整体的收缩功能。     

实验性顿抑心肌的微循环障碍

为了探讨顿抑心肌微循环改变及机制，制备左前降支冠状动脉不同阻断时间(15min和60min)后再灌注犬心肌顿抑模型，在不同观察时间点静脉注射舍全氟丙烷声振白蛋白微泡造影剂，采用二次谐波成像和间歇发射技术行心肌声学造影，计算心肌声学造影图像上心肌视频密度峰值、心肌声学造影曲线上升斜率和曲线早期下降斜率，测定相应时间点冠状静脉窦血乳酸浓度，结果发现，心肌顿抑早期心肌视频密度峰值显著增高，1h后恢复至结扎前水平；再灌注期顿抑区与正常区视频密度峰值比值、心肌声学造影曲线上升斜率比值、心肌声学造影曲线早期下降斜率比值显著高于左前降支冠状动脉结扎前，随着再灌注时间的延长比值逐渐回降；再灌注期冠状静脉窦血乳酸浓度明显增高。以上结果提示，心肌顿抑早期心肌微循环处于“高动力”状态，血流灌注增加与排空加快并存；顿抑心肌缺氧代谢加强；心肌内微循环短路可能是心肌顿抑微循环障碍的机制。     

选择性逆向冠状静脉搭桥术后一氧化氮和内皮素的变化

目的探讨选择性逆向冠状静脉搭桥术对犬心肌缺血模型一氧化氮和内皮素的影响及其意义。方法16只健康成年杂种犬,随机分成缺血组(n=8)和选择性逆向冠状静脉搭桥组(n=8),观察不同时段两组血浆一氧化氮和内皮素含量的变化。并在选择性逆向冠状静脉搭桥组经静脉桥在体灌注墨汁,石蜡包埋后切片观察。结果后降支结扎前,两组血浆一氧化氮和内皮素含量无显著性差异(P>0.05),但结扎后两组血浆一氧化氮和内皮素含量在不同时段比较差异有统计学意义(P<0.01)。显微镜下,经静脉桥灌注的墨汁能在心肌组织间均匀分布。结论选择性逆向冠状静脉搭桥能使心肌得到有效灌注,通过维持犬心肌缺血模型血浆一氧化氮及内皮素水平,从而减轻心肌内皮细胞损害,保护心脏功能。     

冠状静脉向动脉转化的研究进展

冠状动脉粥样硬化性心脏病(CHD)病理特征为不稳定粥样硬化斑块破裂或糜烂基础上血小板聚集、并发血栓形成、冠状动脉痉挛收缩、微血管栓塞导致急性或亚急性心肌供氧的减少和缺血加重,有研究表明冠状静脉可向冠状动脉转化。本文综述了血管生成的分类、冠状静脉向动脉转化的过程、冠状静脉向动脉转化的临床意义和潜在治疗靶点的探索,为今后冠状动脉再生提供治疗依据。     

镁合金可降解的肝素及bFGF支架在心肌血运重建中的应用研究

目的:探讨镁合金可降解联合肝素及碱性成纤维细胞生长因子(bFGF)支架改善心肌缺血区灌注情况。方法: 对18只小猪通过结扎前降支冠状动脉建立急性心肌梗死模型,然后随机分为3组(每组6只),A组为对照组,B组为心肌打孔+镁合金复合缓释肝素可降解支架植入组,C组为心肌打孔+镁合金可降解复合缓释肝素和bFGF支架植入组。在B和C组中,于心肌梗死区采用自制高速钻孔器由心外膜打两个直径为2 mm的透壁孔道,每个孔道内植入1枚支架。6周后,用Image Pro Plus 6.0软件量化各组新生血管的密度。于治疗前和治疗后6周,用SPECT结合软件Emory Cardiac Toolbox分析心肌灌注缺损区域质量百分率,超声学指标左室舒张末直径(LVEDD)、右室收缩末直径(LVESD)、左心室射血分数(LVEF)评价心脏的功能。结果: 治疗后6周,B组和C组LVEF及心肌灌注质量缺损较A组明显改善（P<0.05）;C组中新生血管密度百分率较A组和B组显著改善（P<0.01）。结论: 镁合金复合肝素及bFGF可降解支架能够显著增加缺血心肌新生血管的密度,改善缺血部位心肌的血流灌注,进而提高心脏功能。     

犬急性缺血再灌注左室局部功能与心肌细胞凋亡

目的应变率成像观察犬急性缺血再灌注后左心室局部功能,缺血局部心肌细胞凋亡及Caspase3表达的变化。方法健康杂种犬30只,分为对照组(10只),缺血组(10只),再灌注组(10只)。缺血组于第1对角支1cm以下套扎左冠状动脉前降支30min,再灌注组套扎30min后再灌注120min,对照组游离左冠状动脉前降支不结扎。超声心动图左室收缩期应变率测量左室局部收缩功能,TUNEL法检测缺血区心肌细胞凋亡指数,免疫组化法测缺血心肌细胞Caspase3的表达。结果结扎30min后,缺血组左室前壁缺血节段(中间段)收缩期应变率明显降低(-0.54±0.23)(P<0.01)。并出现收缩后压缩(postsystoliccompression,PSC),再灌注120min后缺血节段的应变率有所恢复(-0.89±0.43),但仍低于对照组(P<0.05)。缺血组缺血区心肌TUNEL阳性细胞指数与对照组比较无显著性差异(2.9±1.3比对照组2.7±1.7)(P>0.05);再灌注组缺血区心肌TUNEL阳性指数明显增加(25.1±3.3)(P<0.01)。缺血区心肌细胞Caspase3表达升高,(20.0±3.1比对照组4.7±2.4)(P<0.01),再灌注组Caspase3表达进一步增强(P<0.01)。结论急性心肌缺血再灌注促凋亡基因Capase3激活,缺血心肌细胞凋亡可能为其早期改变,应变率成像可以评价早期心肌局部收缩功能。     

冠状静脉窦逆行灌注血管内皮生长因子基因对心肌梗死兔心电稳定性的影响

目的观察经冠状静脉窦逆行灌注血管内皮生长因子基因(pAdtrackCMV-VEGF165)对心肌梗死兔心电稳定性的影响。方法20只新西兰大白兔随机分为实验组(基因治疗组)和对照组,两组动物常规全麻,暴露心脏,结扎左室支建立心肌梗死模型,冠状静脉窦插管,实验组逆行灌注pAdtrackCMV-VEGF165,对照组以生理盐水对照,2周后于右室心尖部及流出道行心内程序刺激,观察心律失常诱发情况,并检测左室前壁心肌血管密度。结果对照组恶性心律失常的诱发率显著高于实验组(77.78%vs30.00%,P<0.01);基因治疗组心肌血管密度明显高于对照组(P<0.01)。结论经冠状静脉窦逆行灌注pAdtrackCMV-VEGF165可增加缺血心肌内血管密度,提高缺血心肌的心电稳定性,减少严重心律失常的发生。     

超声微泡造影观测钬激光心肌激光再血管化的实验研究

目的：应用经静脉注射造影剂心肌超声微泡造影探讨激光心肌再血管化的机制及对心肌缺血的治疗效果。方法：部分钳闭犬的冠状动脉前降支形成急性心肌缺血模型，用钬激光在缺血区进行心肌激光再血管化，并在缺血前、缺血后及激光打孔后取左室短轴切面进行超声微泡造影。结果：缺血后心肌超声微泡声学密度较缺血前明显降低（Ｐ＜０．００１），心肌激光再血管化后，缺血区超声微泡声学密度较缺血时明显升高（Ｐ＜０．００１），接近正常心肌超声微泡声学密度（Ｐ＞０．０５），激光再血管化区心肌超声微泡较正常心肌提前显像。结论：心肌激光再血管化可即刻明显缓解心肌缺血，使缺血区血流灌注明显改善。经静脉注射造影剂进行心肌超声微泡造影可作为观测和评价心肌激光再血管化的可靠手段，钬激光心肌再血管化的中远期效果尚待观察。     

冠状静脉窦逆行灌注心肌保护

随着各种心脏直视手术的飞速发展,心肌保护技术也在不断提高和深入研究。冠状动脉灌注技术已被公认为是一种安全有效的心肌保护方法。但近几年来,许多国外学者对冠状静脉窦逆行灌注保护心肌的研究兴趣尤浓。一、冠状静脉的解剖及其生理心脏静脉有两个相互关连的系统。心脏大部分血经心外膜下静脉汇合流入大的心静脉而进入右房。这称为“大系统”,其中包括①经冠状静脉窦流入右房的血管(冠状静脉前降支、左室后静脉、Marshall 斜静脉、心中静脉及流入心大静脉的心小静脉),②直接流入右房的血管(心前静脉)。该系统仅在汇合入大静脉的入口处有单向静脉瓣外,无其它静脉瓣。“小系统”或深静脉系统包括直接流入心腔的血管:动脉心腔血管、动脉血窦血管及 thebesian 静脉。动脉心腔血管实际上是连接动脉与毛细血管的管道,不与心腔相通,流动方向呈双     

Percutaneous approach to a stent-based ventricle to coronary vein bypass (venous VPASS): comparison to catheter-based selective pressure-regulated retro-infusion of the coronary vein.

AIMS: Percutaneous stent-based ventricle-to-coronary vein bypass (venous VPASS) is a new approach to chronic venous arterialization as a treatment modality in an otherwise no option patient with coronary artery disease. In this study, the efficacy of venous VPASS was compared with catheter-based selective pressure-regulated retro-infusion of arterial blood during acute ischaemia. METHODS AND RESULTS: In seven pigs, venous VPASS was established using a percutaneous ultrasound-guided puncture from the anterior cardiac vein to the left ventricle, with subsequent implantation of an ePTFE-covered stent graft. During left anterior descending artery (LAD) occlusion, coronary venous pressure in the distal anterior cardiac vein increased to 55+/-4 mmHg under conditions of venous VPASS compared with 78+/-5 mmHg during selective pressure-regulated retro-infusion. Significant preservation of regional myocardial function was observed during venous VPASS (67+/-6% baseline) and during selective retro-infusion (83+/-4%) compared with control LAD occlusion (0.4+/-2%). CONCLUSION: Percutaneous implantation of a PTFE covered stent (venous VPASS) was feasible and associated with significant preservation of regional myocardial function during acute ischaemia in pigs at reasonable levels of mean coronary venous pressure to avoid tissue damage during chronic application.     

Catheter-based ventricle-coronary vein bypass.

The goal of this study was to investigate the feasibility of a catheter-based ventricle-to-coronary vein bypass (VPASS) in order to achieve retrograde myocardial perfusion by a conduit (VSTENT) from the left ventricle (LV) to the anterior interventricular vein (AIV). Percutaneous coronary venous arterialization has been proposed as a potential treatment strategy for otherwise untreatable coronary artery disease. In an acute setting, the VSTENT implant was deployed percutaneously using the VPASS procedure in five swine. Coronary venous flow and pressure patterns were measured before and after VSTENT implant deployment with and without AIV and left anterior descending artery (LAD) occlusion. In a separate chronic pilot study, the VPASS procedure was completed on two animals that had a mid-LAD occlusion or LAD stenosis. At day 30 post-VPASS procedure, left ventriculography and magnetic resonance imaging (MRI) were performed to assess the patency and myocardial viability of the VSTENT implants. Pre-VSTENT implantation, the mid-AIV systolic wedge pressure was significantly lower than LV systolic pressure during AIV blockage (46 +/- 19 vs. 90 +/- 16 mm Hg; P < 0.01). The VSTENT implant deployment was performed without complication and achieved equalization of the AIV and LV systolic pressures and creation of retrograde flow in the distal AIV (maximal flow velocity: 37 +/- 7 cm/sec). At day 30 post-VPASS procedure, left ventriculography showed VSTENT implant patency. MRI perfusion images demonstrated myocardial viability even with an LAD occlusion. Coronary retrograde perfusion using the VPASS procedure is feasible and may represent a potential technique for end-stage myocardial ischemia.     

云芝多糖防止缺血再灌注心肌早期损伤

为了探讨云芝多糖对心肌缺血再灌注损伤的预防作用，制备犬心肌缺血再灌注损伤模型，输血再灌注组不用药物干预，云芝多糖组手术前2天每天口服云芝多糖150mg/kg。在缺血再灌注过程不同时间点测定左心室舒张压，超声心功能和冠状静脉窦血浆丙二醛浓度，心肌标本行透射电镜检查。结果发现，缺血再灌注组再灌注前和再灌注早期左心室舒张压显著升高，云芝多糖组仅再灌注前左心室舒张压升高，再灌注前两组缺血心肌节段收缩期增厚百分率显著下降，并表现为矛盾运动，再灌注期两组缺血心肌节段收缩期增厚百分率呈进行性改善，至再灌注120min两组均未恢复至结扎前水平，且云芝多糖组显著高于相应时间咪缺血再灌注组；左心室射血分数的变化趋势与缺血心肌节段收缩期增厚百分率相似，但恢复较快，云芝多糖组于再灌注90min即恢复至结扎前水平。缺血再灌注组再灌注期丙二醛浓度明显升高，至再灌注120min尚未恢复至结扎前水平。而云芝多糖组再灌注早期丙二醛浓度升高，但回降较快，于再灌注30min即恢复至结扎前水平，缺血再灌注组心肌组织水肿，心肌细胞少部分肌丝断裂，收缩带模糊，线粒体轻度肿胀，脱颗粒，胞质水肿；云芝多糖组心肌组织除轻微水肿外，未见其它明显结构改变，结果提示，云芝多糖对缺血再灌注早期心肌有显著保护作用。     

脂质胞壁酸诱导的预适应对自发性高血压大鼠心肌缺血再灌注损伤的保护作用

目的:探讨脂质胞壁酸(LTA)诱导的延迟预适应对自发性高血压大鼠(SHR)心脏缺血/再灌注(I/R)损伤的保护作用及诱导型一氧化氮合酶(iNOS)是否参与其作用。方法:采用结扎左冠状动脉前降支30min,再灌注复制大鼠心肌I/R模型,结扎前24h注射LTA,检测心肌再灌注60min后血清心肌型肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH),并用dUTP缺口末端标记法检测心肌细胞凋亡,用Western Blot方法检测凋亡蛋白Bcl-2和Bax的蛋白表达。同时采用实时RT-PCR技术和Western Blot方法分别检测心肌再灌注末iNOS mRNA和蛋白的表达。结果:与I/R组比较,LTA预适应组能显著减少室性心律失常(VA)评分值(P<0.01);LTA预适应还能明显减少I/R后血清CK-MB和LDH的漏出(P<0.01,P<0.05),减少心肌细胞凋亡(P<0.01),凋亡相关蛋白Bcl-2表达明显上调(P<0.01),而Bax蛋白表达则下调(P<0.01)。再灌注末,预适应组iNOS mRNA的平均相对表达量较I/R组增加了0.71倍(P<0.01),LTA预适应组iNOS蛋白的表达量较I/R组增加了0.96倍(P<0.05)。不论在LTA预适应前或缺血前期给予iNOS抑制剂氨基胍或是单独给予氨基胍,上述观测指标均与I/R组比较差异无统计学意义。结论:LTA预适应能显著减轻SHRI/R导致肥厚心肌的坏死和细胞凋亡,iNOS/NO作为触发和效应环节在介导LTA预适应中发挥关键作用。     

超速心室起搏预处理介导心肌保护作用的实验研究

为探讨超速心室起搏 (ventricularoverdrivepacing,VOP)预处理的心肌保护作用及其可能机制。将 2 0只兔随机分为 4组 :①对照组 :右心室留置起搏电极 70min ,1h后结扎冠状动脉左前降支 6 0min ,再放松 90min ,造成缺血再灌注模型。②起搏组 :缺血再灌注前予 5 0 0次 /分起搏右心室 10min× 5次 ,每次间歇 5min。③起搏 +8 苯茶碱 (8 PT)组 :缺血再灌注前使用腺苷受体阻滞剂 8 PT并右心室起搏。④ 8 PT组 :缺血再灌注前静脉注射 8 PT。各组动物于起搏前后或相应时段及缺血再灌注期测定血流动力学和腺苷含量的变化 ;以氯代三苯四氮染色测量各组心肌梗死面积百分比。结果 :起搏组心肌梗死面积百分比较对照组减少 5 1.5 5 % ,P <0 .0 1;缺血再灌注期 ,左室收缩及舒张功能均较对照组改善。起搏 +8 PT组和 8 PT组与对照组比较 ,在梗死面积百分比、左室功能等方面无显著差异。起搏组血清腺苷含量于预处理时一过性增高 ,并在缺血期再度明显增高。结论 :VOP预处理能缩小心肌梗死面积并改善左室功能 ,腺苷可能是其保护作用的机制     

计算机辅助心肌造影负荷超声定量评价心肌灌注及局部收缩功能

目的 探讨计算机辅助心肌造影负荷超声(MCSE)定量评价心肌灌注和局部收缩功能的应用价值.方法 采用急性阻断再灌注左室支建立兔模型,根据阻断和再灌注时间分为两组:阻断30 min后再灌注60 min(Ⅰ组)和阻断120 min后再灌注60 min(Ⅱ组).分别在基础状态、阻断、再灌注和多巴酚丁胺负荷(5、10、15和20 μg·kg-1·min-1)行心肌造影超声心动图,造影图像经自制计算机辅助软件处理后,自动标出每个节段的标化造影剂密度(CI),根据标化CI值,彩色编码标记为:0～ -20像素(pix)黄色、-21～ -40 pix蓝色、-41～ -70 pix绿色以及＜-70 pix红色.分别计算出阻断时和再灌注后红色编码区面积,并与荧光微球染色和氯化三苯基四氮唑染色面积对照分析.同时测量各阶段危险心肌的收缩期室壁增厚率(WT).结果 (1)阻断时,危险心肌的WT降到零点或呈负值,CI明显低于基础状态,红色编码区面积与荧光染色危险心肌面积呈正相关(r=0.91,P＜0.01).(2)再灌注和多巴酚丁胺5μg·kg-1·min-1后,各组危险心肌的WT和标化CI仍减低.以标化CI-70 pix为截断值,识别梗死节段的敏感性为95%,特异性为87%.红色编码面积与氯化三苯基四氮唑染色梗死心肌面积呈正相关(r=0.89,P＜0.01).(3)随着多巴酚丁胺剂量的增加,Ⅰ组的标化CI恢复至基础状态,WT逐渐增加超过基础水平,但Ⅱ组仍保持较低水平.结论 计算机辅助心肌造影负荷超声可以定量评价心肌灌注和局部收缩功能,是识别顿抑和梗死心肌安全可行的方法.     

心肌顿抑中的氧化应激作用及氨基胍干预的效果

背景氧化应激的超氧阴离子(O-.2)可与细胞一氧化氮合酶(NOS)释出的一氧化氮(NO)结合,生成过氧亚硝酸阴离子(ONOO-)。ONOO-是氧化应激各种产物[如O2.-、H2O2、羟自由基(.OH)等]之一,统称为反应性氧族(ROS)。ROS在心肌顿抑中的作用研究不多,氨基胍作为NOS抑制剂对ROS的作用也不清楚。目的探讨ONOO-在心肌顿抑发生中的作用和机制以及氨基胍的干预作用。方法24条雄性杂种犬,随机分为4组:1)短顿抑组[左前降支冠状动脉(LAD)阻断15min/再灌注120min];2)长顿抑组(LAD阻断60min/再灌注120min);3)氨基胍组[LAD阻断60min/再灌注120min加一氧化氮合酶抑制剂氨基胍(100mg/kg)干预];4)假手术组。在不同观察时间点测定超声心功能和冠状静脉窦血浆NO浓度。实验完毕后心肌标本行电镜检查,并行硝基酪氨酸免疫组化检查以证实是否有ONOO-生成。结果1)LAD结扎后缺血心肌节段收缩期增厚百分率和左室射血分数显著下降,缺血心肌节段表现为矛盾运动;再灌注开始后心肌节段收缩功能和左室射血分数呈进行性改善,短顿抑组和氨基胍组心功能的恢复快于长顿抑组。2)短顿抑组和长顿抑组再灌注期血浆NO浓度明显升高,氨基胍组再灌注期血浆NO浓度无显著升高。3)短顿抑组顿抑心肌硝基酪氨酸免疫组化染色见阳性染色的心肌细胞灶;长顿抑组见较大、较多的强阳性染色心肌细胞灶,主要是胞浆尤其横纹处染色较深;氨基胍组顿抑心肌偶见心肌细胞弱阳性染色。4)透射电镜观察发现,短顿抑组心肌细胞偶见线粒体轻度脱颗粒;长顿抑组心肌细胞部分肌丝断裂,收缩带溶解,线粒体肿胀、脱颗粒,胞质水肿;氨基胍组心肌超微结构保存良好。结论1)顿抑心肌生成NO增多伴ONOO-形成;2)ONOO-主要攻击的蛋白质对象是肌丝上的蛋白质;3)氨基胍抑制顿抑心肌过多的NO生成,显著减少ONOO-形成,并对顿抑心肌的超微结构和功能有明显保护作用。     

Effects of ischemia on myocardial function during rapid left ventricular pacing

INTRODUCTION: Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. METHODS: In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. RESULTS: Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. CONCLUSIONS: During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.     

Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.     

Diannexin reduces no-reflow after reperfusion in rabbits with large ischemic myocardial risk zones

Introduction and Aims : In patients with ST‐segment elevation myocardial infarction who receive percutaneous coronary intervention and stenting, a large zone with no‐reflow is associated with adverse outcomes. During myocardial ischemia/reperfusion, phosphatidylserine (PS) translocates to the surface of endothelial cells triggering attachment of platelets and leukocytes, thus impairing microvascular blood flow. Diannexin, a recombinant dimer of the endogenous human annexin V protein, binds PS and thus inhibits the adverse effects of PS. It has been shown to attenuate postischemic reperfusion injury in several experimental models. We speculated that Diannexin would reduce no‐reflow in the heart after coronary artery occlusion (CAO) and reperfusion. Rabbits received: (1) Diannexin 5 min pre‐CAO (diannexin pre ischemia [DPI], 400 μg/kg, n = 17), or (2) Diannexin 5 min pre‐coronary reperfusion (diannexin pre reperfusion [DPR], 400 μg/kg, n = 20), or (3) saline (Cont, n = 18), with 30 min CAO and 3 h reperfusion. In a secondary analysis, rabbits were divided into two groups based on the overall average risk zone size of 29% of the left ventricle (LV): small (<29% of LV) and large (>29% of LV). Results: Overall, risk zones and infarct size, and the no‐reflow zone were similar in all groups. In hearts with large risk zones the no‐reflow area was significantly smaller in both drug‐treated groups (DPI, 22 ± 5% and DPR, 22 ± 3% vs. control 40 ± 3%, P < 0.006), the hemorrhagic areas were significantly smaller, and infarct size was reduced at the P < 0.06 level compared with control. In animals with small risk zones there were no significant differences. Diannexin treatment did not affect hemodynamics or LV function. Conclusion: Diannexin was cardioprotective in rabbits with a severe ischemic insult. This is important, because large infarcts accompanied by no‐reflow in humans are associated with increased complications. In animals with small risk zones, no significant drug effect was observed.