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。     

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O-·2、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15 min/再灌注120 min];2)长顿抑组(LAD阻断60 min/再灌注120 min);3)氨基胍组[LAD阻断60 min/再灌注120 min加一氧化氮合酶抑制剂氨基胍(100 mg/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.     

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。     

超声心肌造影同步检测犬顿抑心肌血流灌注的实验研究

目的　探讨心肌超声造影评判心肌顿抑的可能性和价值。方法　结扎犬左前降支冠状动脉不同时间 (1 5、6 0min)后再灌注 1 2 0min ,在不同观察时间点静脉注射含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超声造影 ,以心肌视频密度峰值表示心肌血流灌注 ,顿抑区与正常区视频密度峰值比值表示顿抑区相对血流灌注。每次心肌超声造影后 ,用超声诊断仪测得心肌节段室壁厚度 ,计算室壁节段收缩期增厚百分率。实验完毕后 ,心肌标本行氯化三苯四唑染色和普通病理切片HE染色光镜检查。结果　 (1 )动物心肌顿抑模型建立的成功率1 0 0 %。 (2 )两组再灌注前缺血心肌节段收缩期增厚百分率显著下降 ,再灌注后逐渐改善 ,但至再灌注1 2 0min尚未恢复至结扎前水平。 (3)两组再灌注早期顿抑心肌视频密度峰值增高 ,随后逐渐恢复至结扎前水平 ;两组再灌注期心肌视频密度峰值比值的变化与顿抑心肌变化相似 ,惟恢复较慢。结论　心肌超声造影结合超声心功能测定能可靠地评判心肌顿抑。     

一氧化氮对犬心肌顿抑心功能的影响

目的探讨心肌顿抑(myocardialstunning,MS)时局部组织一氧化氮(NO)含量的变化,及补充或抑制NO对顿抑心肌功能的影响.方法将35条犬随机分为5组(每组7条),即MS组、亚硝基左旋精氨酸甲酯(NG-nitro-L-argininemethylester,L-NAME)组、左旋精氨酸(L-Arginine,L-Arg)组、3-morpholinosydnonimine(Sir-1,一种NO供体)再灌注组及对照组.实验组均通过开胸阻断左冠状动脉前降支(LAD)15min再灌注3h建立MS模型,采用微电极法和Greiss法检测心肌表面及冠状窦血中NO含量变化,根据血流动力学监测及经食管彩色多普勒血流仪(transesophagealechocardiography,TEE)观察心功能及缺血节段室壁运动的变化.结果(1)阻断犬LAD15min后,所有犬均发生MS,主要表现为前壁室壁运动减弱,左室±dp/dt减低;(2)缺血再灌注期,顿抑心肌合成NO减少,L-Arg及Sin-1可明显增加顿抑组织的NO含量,而L-NAME则降低NO含量;(3)再灌注L-Arg及Sin-1在早期即可明显减轻顿抑心肌的室壁运动障碍,使心功能相对改善.结论心肌顿抑时局部顿抑组织NO含量减低,再灌注早期补充NO供体Sin-1及前体L-Arg可明显改善顿抑心肌的缩舒功能,而用L-NAME阻断NO的合成后则无此作用.     

缓激肽对兔顿抑心肌功能的保护作用

本文报道缓激肽（ＢＫ）对兔顿抑心肌功能的作用。结果显示:结扎兔冠脉左室支１５ｍｉｎ，再灌注３０ｍｉｎ，左室收缩及舒张功能进行性下降；结扎前左室内灌注生理盐水对顿抑心肌功能无明显影响；结扎前左室内灌注缓激肽后，再灌注３０ｍｉｎ时左室功能恢复至正常水平。提示:缓激肽对兔顿抑心肌的功能具有保护作用。     

实验性缺血再灌注心肌顿抑与一氧化氮的关系及东莨菪碱对其影响

目的探讨体外循环缺血再灌注心肌顿抑与心肌一氧化氮（ＮＯ）产生之间的关系及东莨菪碱对其影响。方法１２只绵羊，随机均分为：对照组和实验组：即东莨菪碱治疗组。常规建立体外循环，对照组主动脉阻断同时灌注冷停搏液（本院配方）；实验组，停搏液中加入东莨菪碱１７．５μｇ／ｋｇ。于主动脉阻断前、再灌注５分钟、再灌注３０分钟取冠状窦血检测ＮＯ、肌酸激酶（ＣＫ）、环磷酸鸟苷（ｃＧＭＰ）浓度，取心肌测定丙二醛（ＭＤＡ）含量，相应时点监测心功能。结果再灌注５分钟和３０分钟时，对照组心肌血的ＮＯ、ＣＫ、ｃＧＭＰ、ＭＤＡ均明显升高，与主动脉阻断前相比差异有显著性（Ｐ＜０．０５或＜０．００１），和实验组相同时间点相比差异有显著性（Ｐ＜０．０５或＜０．０１）。两组再灌注５分钟和３０分钟时心肌功能均降低，对照组较实验组更为显著。再灌注后ＮＯ的变化与心肌ＭＤＡ和ＣＫ之间呈正相关（Ｐ＜０．０５和０．０１）。结论缺血再灌注心肌顿抑与ＮＯ产生增加有关，大量释放的ＮＯ提高心肌组织ｃＧＭＰ，参与心肌细胞脂质过氧化损害心肌功能。东莨菪碱减少ＮＯ产生、保护顿抑心肌的作用可能与其抗脂质过氧化有关。     

微血管顿抑

微血管顿抑(Microvascular Stunning)指心肌暂时性缺血再灌注后出现的微血管功能可逆性损伤,亦称微血管再灌注损伤。主要表现为微血管的扩张功能受损,冠脉储备减低,微血管通透性增加以及组织学的相应改变。其可能的发生机制为氧自由基作用,白细胞-内皮相互作用,或二者共同引起。     

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。     

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.     

Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography.

AIMS: We hypothesized that molecular imaging of endothelial P-selectin expression with targeted myocardial contrast echocardiography (MCE) could identify recently ischaemic myocardium without infarction. METHODS AND RESULTS: The microvascular behaviour of P-selectin-targeted (MB(p)) and control (MB(c)) microbubbles was assessed by intravital microscopy of the cremaster muscle in mice. Targeted MCE imaging with MB(p) and MB(c) was performed in mice after brief left anterior descending (LAD) occlusion and reperfusion and in open- and closed-chest controls. Regional wall motion and perfusion by MCE were assessed during occlusion and after reperfusion. On intravital microscopy, ischaemia-reperfusion produced a 10-fold increase (P < 0.01) in venular attachment for MB(p). Attachment for MB(c) was rare. With myocardial ischaemia-reperfusion, LAD occlusion produced hypoperfusion and wall motion abnormalities that resolved after 45 min of reperfusion. At 45 min, signal enhancement in the post-ischaemic region was four-fold greater (P < 0.05) for MB(p) vs. MB(c). MB(p) produced low-level enhancement in non-ischaemic myocardium in all open-chest animals, suggesting P-selectin expression from surgical cardiac exposure. CONCLUSION: Molecular imaging of P-selectin with targeted MCE can identify the presence of recently ischaemic myocardium in the absence of necrosis and after resolution of hypoperfusion and post-ischaemic stunning. This technique can potentially provide a method for risk stratifying patients with acute chest pain.     

Ischemic preconditioning reduces infarct size in swine myocardium

We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia.     

Visualization of risk-area myocardium as a high-intensity,hyperenhanced "hot spot" by myocardial contrast echocardiography following coronary reperfusion: quantitative analysis

OBJECTIVES: We examined whether delayed post-injection imaging of a new ultrasound contrast agent (BR-14) could produce prolonged opacification and hyperenhancement of myocardium subjected to coronary occlusion/reperfusion. BACKGROUND: We hypothesized that ultrasound exposure destroyed BR-14 and eliminated visualization of sustained myocardial opacification from retained microbubbles. METHODS: We studied eight open-chest dogs with 3 h of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Myocardial contrast echocardiography (MCE) was performed before occlusion and 120 min after the onset of both occlusion and reperfusion. Ultrasound imaging was initiated 15 min after injection. Myocardial blood flow (MBF) was assessed by microspheres. RESULTS: Pre-occlusion images revealed uniform opacification of left ventricular myocardium greater than that of the cavity, with a mean intensity of the LAD bed of 8.66 +/- 1.38 dB. During occlusion, MCE resulted in the appearance of a perfusion defect in the LAD risk area (intensity 2.08 +/- 1.10 dB). After 120 min of reperfusion, the LAD risk-area myocardium manifested dense opacification of a higher intensity ("hot spot") than baseline (13.7 vs. 8.7 dB), but with reduced MBF consistent with accumulation of a high concentration of microbubbles. Increased MCE intensity was associated with a greater myeloperoxidase score. CONCLUSIONS: These data establish that contrast opacification by BR-14 may be selectively retained within the perfusion bed of a coronary artery subjected to occlusion/reperfusion. Such opacification exhibits defects with occlusion, manifests hyperenhanced intensity (hot spot) with reperfusion, is associated with the level of myeloperoxidase activity, and conforms to the area of myocardium subjected to altered flow.     

Effect of intracoronary diltiazem on infarct size and regional myocardial function in the ischemic reperfused canine heart

This study was designed to investigate whether intracoronary diltiazem given before reperfusion could enhance myocardial salvage in the canine heart. Twenty-five dogs were subjected to 90 min of coronary occlusion followed by 4 h of reperfusion. The dogs were assigned to one of three experimental groups. The early diltiazem group received intracoronary diltiazem into the distal coronary bed at the onset of coronary occlusion and for 60 min after reperfusion. The late diltiazem group received the same amount of drug beginning 15 min before reperfusion and the control group received saline solution for 90 min of occlusion and 60 min of reperfusion. Infarct size expressed as a percent of the area at risk was significantly smaller in the early and late diltiazem groups (15.6 +/- 3.6% and 21.2 +/- 5.1%, respectively) than in the control group (49 +/- 4.6%) (p less than 0.05). Intracoronary diltiazem restored systolic function of the stunned, previously ischemic tissue to essentially normal preocclusion values. Segmental shortening after reperfusion averaged 21.6% in the early diltiazem group versus 0 +/- 1.7% and 7.3 +/- 4% for the control and late diltiazem groups, respectively (p less than 0.05). Low dose intracoronary diltiazem did not alter hemodynamic variables or myocardial blood flow but did improve segmental shortening 2 and 6 h after reperfusion. These data indicate that intracoronary diltiazem given during occlusion or just before reperfusion increases the salvage of myocardium compared with the salvage achieved by reperfusion alone. These results also suggest that intracoronary diltiazem given during the ischemic period enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pathophysiology of myocardial stunning: reversibility, accumulation and continuity of the ischemic myocardial damage after reperfusion.

In order to understand the pathophysiology of myocardial stunning, reversibility, accumulation and continuity of ischemic myocardial damage after reperfusion should be studied. Then, to analyze these three factors, myocardial function, metabolism and morphology under ischemia and reperfusion were studied in anesthetized, open-chest dogs. When myocardial ischemia was induced by occlusion of the left anterior descending coronary artery, percentage regional systolic shortening (%SS) of ischemic myocardium sharply decreased and became stable 10 min after occlusion. After reperfusion, ischemic myocardium showed active shortening after within 30-min occlusion, but did not after more than 60-min occlusion. During 90-min of ischemia, extracellular K+ concentration (Ke) steeply increased for first 10 min and was almost stable for next 10 min. Then, Ke straightly increased till 90 min. Metabolic rates, calculated from myocardial tissue CO2 and pH, steeply increased for first 20 min and sharply decreased for next 10 min. After 30 min, these two variables were almost stable, near zero. By electron-microscopy with cytochemistry, distribution of Na/K ATPase to myocardial cell membrane was observed to be almost after 15-min occlusion but distinctly sparse with destruction of cell membrane after 30-min occlusion. Therefore, irreversible myocardial damage appears after about 20-min ischemia and is almost complete after 60 min. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia. Although stunned myocardium in a narrow sense is may appear after reperfusion within less than 20-min of ischemia, stunned myocardium in a broad sense may appear within less than 60-min ischemia. When reversible myocardial ischemia (4- or 15-min occlusion) was repeated after short time intervals (20-min reperfusion), %SS of ischemic myocardium was gradually decreased with each ischemic episode. Active shortening of ischemic myocardium disappeared after more than two episodes of 15-min occlusion. Fluctuation of PCO2, pH and Ke of ischemic myocardium was gradually depressed with each occlusion. Metabolic viability of ischemic myocardium was cumulatively depressed by repeated brief occlusion. Naturally, myocardial damage was more severe after repeated 15-min occlusion than after 4-min occlusion. Accumulation of ischemic myocardial damage may arise as brief ischemia, which only induces reversible damage, is repeated. At last, continuity of ischemic myocardial damage was studied. The effect of 5-min occlusion to %SS of ischemic myocardium was apparently reversed after 90-min reperfusion. Early contractile failure was advanced even after very short duration of ischemia. Thus, myocardial function will be latently damaged.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion

To determine the effect of intracoronary perfluorochemical on endothelial cell structure and function, 16 dogs were randomized to receive either low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) or saline after 90 min of proximal occlusion of the left anterior descending coronary artery (LAD). The animals underwent reperfusion for 60 min with the introduction of perfluorochemical or saline 5 to 10 min after the onset of reperfusion. Endothelium-dependent coronary vasodilatory reserve was determined in vivo both at baseline and 1 hr after reperfusion by infusion of acetylcholine and then serotonin into the distal LAD bed in 12 animals (six in each group). Both agonists significantly increased regional flow measured by 133Xe washout in the two groups before occlusion, but at 1 hr after reperfusion only animals given perfluorochemical demonstrated a significant increase in flow. Vasodilatory reserve was assessed in vitro with cumulative dose-response curves to acetylcholine on LAD rings proximal and distal to the snare in all animals. These studies demonstrated a significant reduction in endothelial cell-mediated relaxation of epicardial arterial segments in the ischemic segment of control but not treated animals. Light microscopy revealed the presence of neutrophils within vessels in the ischemic zones in control animals only. Electron microscopy showed capillary obstruction by endothelial cell protrusions and neutrophil and red cell plugging in control animals in the ischemic region but an intact endothelium and predominantly unobstructed capillaries in treated animals. These findings suggest that the structural and functional endothelial damage after reperfusion may be prevented by the administration of intracoronary perfluorochemical after the onset of reperfusion.     

Blockade of adenosine receptors during ischaemia increases systolic dysfunction but does not affect diastolic creep in stunned myocardium

The impact of adenosine receptor blockade on left ventricularsystolic function and diastolic creep in stunned myocardiumwas studied in 20 sodium pentobarbital anaesthetized cats. Acontrol group (n=10) was compared with a group (n=10) whereadenosine receptors were blocked by 8-phenyltheophylline (7.5mg. kg^–1 i.v.) prior to a 10 min occlusion of the leftanterior descending coronary artery. Regional function was assessedby sonomicrometry of the left ventricular anterior wall. Tissueblood flow and haemodynamic measurements were obtained at pre-occlusion,during occlusion, and after 30 and 60 min of reperfusion. Tissueblood flow in the LAD region was low and homogeneous duringcoronary occlusion in both groups. Systolic function assessedby regional shortening and inotropic parameters was significantlymore reduced in the 8-PT treated group (P<0.05). Diastoliccreep and compliance assessed by the end-diastolic pressure-lengthrelationship did not differ between groups. Thus, endogenousadenosine protects against systolic dysfunction, but appearsto have no impact on diastolic creep in stunned myocardium.Furthermore, our results show that the protective effect ofendogenous adenosine is not caused by increased collateral bloodflow into the ischaemic area during coronary artery occlusionor by increased blood flow in the reperfusion period.     

Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion by myocardial contrast echocardiography

Background. Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion.Objective. To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion.Methods. Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas.Results. After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r = 0.79; p < 0.0001).Conclusions. The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.