The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility

Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2(1/2)-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 mug) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is ischemic, collaterals are unresponsive to TNG, suggesting that these collaterals dilate fully when the regions from which they originate become ischemic.     

二维斑点追踪技术评价犬缺血心肌局部功能及侧支循环的应用价值

目的 探讨二维斑点追踪技术评价犬缺血心肌局部功能及侧支循环建立的应用价值.方法 10只杂种犬,结扎左冠状动脉前降支(LAD)主干建立急性心肌缺血模型.分别于术前、LAD结扎后即刻、30、60、180、240、360 min,采集左心室短轴二尖瓣水平及乳头肌水平二维灰阶动态声像图,QLAB软件分析左心室短轴基底部及乳头肌水平12节段心肌整体收缩期平均峰值周向应变(CS)、径向应变(RS)及左室短轴缩短率(LVFS)的变化.实验结束后行心肌组织氯化三苯基四氮唑(TTC)染色.结果 ①与术前相比,LAD结扎术后30～60 min,左心室短轴缺血节段(前间隔、前壁及侧壁)的心肌应变CS及RS收缩期峰值均显著降低(P＜0.05);60 min后CS及RS收缩期峰值均有恢复趋势,但与术前差异仍有统计学意义.非缺血节段后壁及下壁术后部分CS及RS收缩期峰值较术前有所下降(P＜0.05),后间隔CS及RS无明显变化.②与术前相比,LAD结扎术后60～360 min,左心室短轴缺血节段(前间隔、前壁及侧壁)的LVFS均显著降低(P＜0.05),非缺血节段LVFS均无显著改变.③TTC染色结果显示,左心室短轴心肌梗死节段为LAD供血的前间隔、前壁及侧壁,与CS和RS的结果相一致.结论 心肌应变参数CS、RS能够敏感反映急性心肌缺血的范围、程度及侧支循环建立后局部心肌节段应变的变化.     

速度向量成像技术评价犬心肌缺血与梗死状态下左心室节段性旋转特征

目的应用速度向量成像(VVI)技术评价心肌缺血及心肌梗死状态下犬心肌旋转运动特征。方法选用杂种犬12只,在超声实时引导下结扎前降支定量制备前降支轻度狭窄(狭窄率:50%～75%)与完全闭塞模型,应用VVI技术分析前降支结扎前、轻度狭窄与完全闭塞状态下左心室旋转特征的改变。结果 12只杂种犬成功制备前降支轻度狭窄与完全闭塞模型,应用VVI技术对缺血与梗死状态下心肌旋转运动分析结果显示:(1)前降支部分结扎状态下室间隔的旋转角度与圆周应变较正常显著降低(P<0.05);径向应变与应变率较正常差异有统计学意义(P<0.05);(2)前降支完全结扎状态下:前间隔、室间隔、前壁的旋转角度与旋转速度、圆周应变与圆周应变率较正常及部分结扎状态下均显著减低(P<0.05);径向应变与应变率较正常状态下显著降低(P<0.05),与部分结扎状态下比较,差异无统计学意义。结论 VVI技术可以无创、敏感地评价心脏旋转运动。前降支部分结扎状态下心脏的旋转在个别节段已经出现减低,前降支完全结扎后,旋转角度与旋转速度较结扎前、部分结扎后均显著降低,心脏旋转可以更加敏感的反映心脏收缩功能。     

糖尿病患者冠状动脉左前降支远段血流动力学变化的超声研究

目的应用冠脉血流显像技术观察分析糖尿病患者静息状态下左前降支(LAD)远段血流动力学改变,了解该变化与心肌微血管损害之间的关系。方法对31例非胰岛素依赖性糖尿病患者进行冠脉多普勒血流显像检查,观察LAD远段在静息状态下的冠脉血流信号,记录流速曲线,测定收缩期峰值速度(SPV),收缩期速度时间积分(VTIs),舒张期峰值速度(DPV),舒张期速度时间积分(VTId),舒张期加速时间(TPVd),舒张期减速度(DDR)以及舒张期减速时间(DDD),并与正常对照组进行比较。结果31例患者中有2例未测及前降支远段血流,其余29例均能较清晰显示,SPV、DPV与正常对照组比较无显著性意义VTIs、VTId、TPVd和DDD明显低于正常对照组(P<0.01),DDR高于正常对照组(P<0.05)。结论糖尿病患者心肌内微血管的损害可以影响心外膜冠脉的血流动力学,而经胸冠脉多普勒血流显像能直接观测前降支远段冠脉血流,早期发现糖尿病患者潜在的心肌缺血。     

Left main or proximal left anterior descending coronary artery disease: detection by echocardiographic evaluation of interventricular septal function during exercise

Summary. Forty patients with coronary artery disease were studied prospectively to investigate whether stenosis of the left main (LMCA) or left anterior descending coronary artery, proximal to the first septal branch (proximal LAD), could be detected by M-mode echocardiography during exertion. The interventricular septum was visualized in 30 of the patients during bicycle exercise in the semisupine position, all with simultaneous occurrence of electrocardiographic evidence of myocardial ischaemia. Fifteen of these had LMCA or proximal LAD stenosis. Systolic motion and thickening of the septum decreased significantly from rest to peak exercise in patients with LMCA or proximal LAD disease while it increased in those without. The results suggest that M-mode echocardiography during exercise in patients with coronary artery disease might identify those with LMCA or proximal LAD stenosis.     

急性缺血再灌注心肌细胞凋亡及凋亡基因与左室局部功能的实验研究

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，与细胞凋亡及心肌组织中caspase-3 mRNA和蛋白表达的变化。方法 健康杂种犬30只，分对照组（10只），缺血组（10只），再灌注组（10只）。缺血组于第一对角支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数，RT-PCR法检测caspase-3 mRNA的表达，免疫组化法测caspase-3蛋白的表达。结果 结扎30min后，左室前壁缺血节段收缩期应变率明显降低（P〈0.01）。并出现收缩后压缩（PSC），再灌注120min后缺血节段的应变率有所恢复，但仍低于对照组（P〈0.05）。缺血组缺血区心肌TUNEL阳性细胞数与对照组比较无显著性差异;再灌注组缺血区心肌TUNEL阳性数明显增加（P〈0.05）。缺血组缺血区caspase-3 mRNA与对照组比较表达增高（P〈0.05），再灌注组进一步增高（P〈0.01）。缺血组缺血区心肌细胞caspase-3表达升高，与对照组比差异有显著意义（P〈0.05），再灌注组caspase-3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capase-3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缺血早期心肌局部收缩功能。     

Detection of ischemia and new insight into left ventricular physiology by strain Doppler and tissue velocity imaging: assessment during coronary bypass operation of the beating heart.

BACKGROUND AND OBJECTIVES: Detection of myocardial ischemia in humans by strain Doppler and tissue velocity imaging was validated in a novel, experimentally designed study model during coronary bypass operation of the beating heart. METHODS: Assessment of ischemia was made with an opened chest and pericardium inherent in the operative procedure. Longitudinal strain and tissue velocity of interventricular septal regions were measured by transesophageal echocardiography during occlusion of the left anterior descending coronary artery (LAD). RESULTS: Unexpectedly, baseline velocities demonstrated that the apical and basal septum moved toward each other during systole. This occurred when the apex was dislodged from the pericardial sac to obtain access to the LAD, without any change in strain. The preceding motion of all septal regions toward the apex was reestablished after the heart was repositioned within the pericardium. In 16 patients with antegrade LAD flow, strain Doppler detected ischemia during LAD occlusion by disclosing systolic lengthening of the apical septum ( P <.01) and reduced shortening of the mid septum ( P <.05). The location and degree of ischemic changes coincided with the concomitant deterioration of wall motion. Tissue velocity changed in the basal and mid septum ( P <.05) but not in the apical region, explained by tethering effects and the distinctive motion pattern at baseline. There was no evidence of ischemia by invasive hemodynamic measures. In 7 patients with retrograde LAD flow, there were no significant changes in strain or tissue velocity measurements during LAD occlusion. CONCLUSIONS: Strain by Doppler is a sensitive means for detecting myocardial ischemia, also capable of correctly localizing the ischemia, as opposed to tissue velocity assessment. However, velocity measurements provided new physiological information by disclosing the normal longitudinal motion of the heart to be dependent on the pericardial sac enveloping the apex, irrespective of the structural integrity of the pericardium.     

Echocardiographic analysis of systolic and diastolic left ventricular wall motion during transient myocardial ischemia

Left ventricular (LV) wall motion (anterior and posterior) and simultaneous LV pressure were recorded during 30-second left anterior descending (LAD) or circumflex (CX) coronary artery occlusions in open-chest dogs to provide an echocardiographic model of the evolution of wall motion changes during myocardial ischemia. Prominent diastolic echocardiographic motion changes of progressive decrease in LV wall rapid-filling velocities (RFS), slow-filling velocities (SFS), and increased end-diastolic diameter were accompanied by a marked increase in initial and end-diastolic pressures (150% and 70%, respectively; all p < 0.05). Early (within ten seconds) and progressive decrease in rate (SES), amplitude (E), and duration (TTR) of systolic motion were noted with an increased systolic diameter (p < 0.05). Ischemic regions developed a characteristic pattern with early relaxation followed by a diastolic inward motion (DIM). These observations confirm and extend other investigators' findings on the motion of the ischemic myocardium and may be applicable to responses to transient myocardial ischemia noted in humans.     

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。     

Myocardial ultrasonic backscatter for characterization of ischemia and reperfusion: relationship to wall motion

We have previously shown that cardiac cycle-dependent variation of integrated backscatter occurs in normal myocardium. To determine whether myocardial ischemia and reperfusion can be distinguished by real-time integrated backscatter imaging we performed 10 min balloon occlusion of the Left Anterior Descending (LAD) coronary artery followed by reperfusion in 10 closed-chest anesthetized dogs. Images were obtained at baseline, during occlusion, and up to 120 min after reperfusion. We measured the magnitude and delay of cyclic variation of integrated backscatter in segments with and without asynergy. Radiolabeled microspheres were used to verify both ischemia and reperfusion. Ischemic segments exhibited decreased magnitude and increased normalized delay of cyclic variation of integrated backscatter (from 3.3 +/- 0.3 dB to 1.4 +/- 0.2 dB, mean +/- SE; and from 0.95 +/- 0.03 to 1.67 +/- 0.15, respectively, all p less than or equal to 0.001). Reperfusion promptly restored the magnitude of cyclic variation toward normal. However, the delay of the cyclic variation was restored only partially. Wall motion analysis of the ischemic sites revealed persistent abnormalities throughout the reperfusion interval despite return to normal of the magnitude and delay of cyclic variation. Thus, real-time integrated backscatter imaging permits detection and differentiation of changes in myocardial acoustic properties indicative of ischemia and of subsequent reperfusion.     

吗啡对急性心肌梗死再灌注损伤保护效应的实验研究

目的　通过测定急性心肌梗死再灌注损伤模型大鼠的血浆降钙素基因相关肽 (CGRP)、内皮素(ET 1)浓度及心肌梗死面积的变化 ,探索吗啡对急性心肌损伤的保护机制。方法　将 4 0只 SD大鼠随机分为单纯缺血再灌注模型组、吗啡预处理组、吗啡 纳洛酮组和手术对照组 ,每组各 10只。采用戊巴比妥钠(40 m g/ kg)腹腔注射麻醉大鼠 ,采用穿线结扎左冠状动脉前降支制备大鼠心肌缺血再灌注模型。用放射免疫法测定血浆 CGRP和 ET 1浓度 ,同时测定血清中肌酸磷酸激酶同工酶 (CK MB)含量 ;用氯化三苯四唑(TTC)法染色和数码照相计算机图像分析系统计算心肌梗死面积。结果　大鼠左冠状动脉前降支结扎 10 m in时血浆 ET 1和 CGRP浓度较手术对照组显著增高 (P均 <0 .0 1) ;再灌注 4 .5 h时吗啡预处理组血浆 ET 1及 CK MB浓度较结扎 10 m in时显著降低 ,心肌梗死面积也显著缩小 (P均 <0 .0 1) ;而血浆 CGRP浓度则显著增高 (P<0 .0 1) ;吗啡预处理组以上变化较吗啡 纳洛酮组差异有统计学意义 (P均 <0 .0 1)。结论　吗啡预处理可通过显著降低 ET 1而增加 CGRP血浆浓度、缩小心肌梗死面积 ,对急性心肌梗死后再灌注心肌产生保护效应。     

Effect of naloxone on expression of Bcl-2 protein and tumor necrosis factor-alpha in rats with acute myocardial ischemia/reperfusion injury]

OBJECTIVE: To investigate the effect of naloxone on myocardial cell apoptosis and apoptosis-related gene Bcl-2 in rats with acute myocardial ischemia/reperfusion (AMIR) injury, and explore the mechanism of protective effect of naloxone on myocardium. METHODS: Thirty SD rats were randomly divided into three groups (n=10): ischemia/reperfusion group, naloxone preconditioning group (naloxone was injected intraperitoneally 10 minutes before ischemia and 2 hours after reperfusion), and normal control group. The left anterior descending branch (LAD) of rat coronary artery was tied and untied in ischemia/reperfusion group and naloxone preconditioning group to establish the AMIR model in rats. The animals were then sacrificed and hearts were harvested. The expression of Bcl-2 protein was observed by immunohistochemical technique. Radioimmunoassay (RIA) was used to determine tumor necrosis factor-alpha (TNF-alpha) in serum. RESULTS: In the normal control group, there was no Bcl-2 expression and TNF-alpha level was (0.39+/-0.06) mug/L. Higher expression of Bcl-2 and increased TNF-alpha levels were found in ischemia/reperfusion group. The expression of Bcl-2 protein increased significantly [(+++) vs. (+)], and TNF-alpha was significantly lower in naloxone preconditioning group than those in the normal control group [(0.55+/-0.12) microg/L vs. (0.86+/-0.11) microg/L, P<0.01]. CONCLUSION: Naloxone can protect myocardium from AMIR injury by inhibiting the apoptosis of cardiomyocytes induced by TNF-alpha and up-regulating protein expression of bcl-2 gene.     

Ultrasound characterization of acute myocardial ischemia by quantitative texture analysis

In this study we tested the efficacy of quantitative texture analysis in the identification of acute myocardial ischemia using an ultrasound data acquisition system that digitizes and stores echocardiographic data in polar format. In nine closed-chest dogs, data were acquired before and after coronary occlusion using a 2.4 MHz echocardiographic system. Regions of interest were analyzed at end-diastole and end-systole from the ischemic area and normal area at the same depth of field. Ultrasound data were evaluated using previously reported quantitative gray level texture measures. After occlusion, texture changes indicative of ischemia were found in systolic images. The directional component of the data analysis was important; analysis in the azimuthal direction was more accurate than in the axial direction. Six texture measures exhibited significant changes in the ischemic region from control to occlusion when analyzing data in the azimuthal direction. One false positive result occurred (significant texture change in the normal region from control to occlusion) in the azimuthal direction. Several false positive alterations in the normal regions from control to occlusion were found when the texture was evaluated in the axial direction. For accurate assessment of ischemic changes, preocclusion image data were required. We conclude that quantitative echocardiographic texture analysis using polar format data can identify subtle changes in myocardial texture such as that due to acute ischemia, using data acquired through the chest wall.     

Effect of efonidipine, a novel dihydropyridine derivative, on myocardial metabolic changes induced by coronary artery ligation in dogs: comparison with nifedipine

Summary— Efonidipine is a dihydropyridine derivative having a vasodilating action, which is slower in onset and longer in duration than that of nifedipine. In the present study, we compared the effects of efonidipine with those of nifedipine on the ischemic myocardial metabolism in anesthetized dogs. The heart was made ischemic by ligating the left anterior descending coronary artery (LAD) completely for 3 or 30 min. Efonidipine or nifedipine was injected intravenously, 10 or 3 min, respectively, before the start of LAD occlusion. Efonidipine (0.01 or 0.03 mg/kg) decreased both blood pressure and heart rate, whereas nifedipine (0.003 mg/kg) decreased blood pressure and increased heart rate. The magnitude of decrease in mean blood pressure induced by 0.03 mg/kg efonidipine was similar to that induced by 0.003 mg/kg nifedipine. Although efonidipine did not modify the changes in myocardial carbohydrate metabolism induced by ischemia, it attenuated the ischemia-induced decrease in the myocardial level of adenosine triphosphate and energy charge potential. Nifedipine, however, did not modify the changes in both myocardial energy and carbohydrate metabolism induced by ischemia. The results suggest that efonidipine has a cardioprotective effect in the dog, probably because of its negative chronotropic effect.     

Myocardial electrical activity does not affect myocardial electrical impedance measurements

Objective  Myocardial electrical impedance (MEI) has shown to be an effective indicator of myocardial ischemia. We have previously developed a novel monitor for measuring MEI in near-real time. The object of this study was to test whether drug-induced changes in the frequency of the periodic myocardial electrical activity, as measured by the heart rate (HR), affect MEI measurements made with our monitor. Methods  Thirty dogs were randomly assigned to one of three study groups (placebo, isoproterenol or esmolol) and then anesthetized with sodium thiamylal, intubated, ventilated, given isoflurane, and had venous, arterial, and pulmonary artery catheters placed. Median sternotomy was performed to facilitate myocardial exposure and to allow the left anterior descending (LAD) coronary artery to be isolated. Following baseline measurements, saline (control), isoproterenol or esmolol was administered and the LAD coronary artery was occluded in a timed sequence in order to study the effects of heart rate changes and demonstrate induced myocardial ischemia on MEI. Results  Isoproterenol raised the HR and esmolol lowered the HR without affecting our MEI measurements. Myocardial electrical impedance increased during LAD coronary artery occlusion in all groups, as previously shown. Conclusion  These results demonstrate that our MEI monitor is unaffected by the frequency of the periodic myocardial electrical activity that generates the HR. Dzwonczyk R, del Rio C, McSweeney TD, Zhang X, Howie MB. Myocardial electrical activity does not affect myocardial electrical impedance measurements.     

组织多普勒成像在急性心肌缺血心功能异常中的实验研究

目的 运用组织多普勒成像（TDI）技术对急性心肌缺血区域和二尖瓣环侧壁处的运动速度、移动振幅进行检测,探讨TDI在急性心肌缺血、心肌梗死中的应用价值。方法 10只开胸猪结扎左冠状动脉前降支（LAD）,通过TDI技术速度模式检测缺血区域和心尖四腔观二尖瓣环侧壁处的色泽变化及收缩、舒张期运动速度（VS,VE,VA）、移动振幅（CD,MDe,MDa）、等容收缩期时间,并与基础状态对照分析。结果 LAD结扎后,缺血区域和二尖瓣环处色泽暗淡,局部心肌色彩缺失,结扎15s时收缩期、舒张早期运动速度、移动振幅显著降低,等容收缩期时间延长。结论 TDI技术能准确反映血梗死区域运动异常,精确测定局部收缩、舒张期运动速度、移动振幅,尤其二尖瓣环处的运动能反映整体心肌的运动,为临床早期评价局部心肌缺血及心功能异常提供了一种无创性的检查手段。     

宽高频超声对大鼠心肌梗死模型左心室形态结构变化的分型研究

目的探讨不同病理分型大鼠心肌梗死模型左心室形态结构变化的超声表现。方法对48只SD大鼠实施开胸手术,其中41例结扎左冠状动脉前降支(LAD)(实验组),7例假手术组仅打开心包膜。术后4周采用10~22MHz的宽高频超声测定左心室形态、结构和功能,并与病理结果进行比较分析。结果按照心肌梗死的轻、中、重度病理分类,不同梗死程度的左心室形态在二维超声显像中表现为短轴和长轴的不同变化;心肌梗死大鼠左心室内腔和肌壁的几何形态失真,表现为梗死部位即瘢痕组织部位肌壁薄、回声增强且不均匀;斑痕组织的部位、大小与病变程度相关,并与病理改变相一致。轻、中、重度心肌梗死模型心肌前壁均变薄,中度涉及侧壁,重度后壁亦有改变。随着心肌梗死程度的加重,左心室缩短分数逐渐下降。结论经胸宽高频超声心动图可以在大鼠心脏的短轴和长轴切面直接显示心肌梗死发生的部位、范围和程度,准确评价大鼠左心室形态结构和功能变化。     

Calcitonin gene-related peptide receptor antagonism does not affect the severity of myocardial ischemia during atrial pacing in dogs with coronary artery stenosis

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide that also has potent vasodilator activity. There are conflicting preclinical reports regarding the effect of CGRP receptor antagonism in the setting of myocardial ischemia. The present study was conducted in a canine model in which regional myocardial ischemia was reproducibly evoked by serial periods of atrial pacing (80 beats per min above baseline rate) in the presence of a 40% stenosis of the left anterior descending (LAD) coronary artery. Ischemia severity was quantitated by changes in unipolar epicardial electrograms (EG) recorded in the area of ischemia. In validation studies, the calcium entry blocker diltiazem reduced ischemia severity (before versus after treatment: DeltaEG, 1.92 +/- 0.23 versus 0.54 +/- 0.24 mV; p < 0.05) and tended to increase LAD flow (7.7 +/- 0.7 versus 9.4 +/- 1.4 ml/min; p = 0.10), whereas the coronary constrictor serotonin increased ischemia severity (before versus after treatment: DeltaEG, 2.11 +/- 0.44 versus 4.90 +/- 1.46 mV; p < 0.05) concomitant with a reduction in LAD flow (9.1 +/- 1.1 versus 5.4 +/- 1.5 ml/min; p < 0.05). A 30 microg/kg/min i.v. infusion test dose of the CGRP receptor antagonist CGRP((8-37)) was validated by demonstrating complete block of the depressor effects of exogenous i.v. 0.03 to 0.3 microg/kg CGRP. This dose of CGRP((8-37)), administered either intravenously or intra-atrially, had no effect on ischemia severity or paced LAD flow, indicating no intrinsic effect of CGRP receptor antagonism on the severity of acute myocardial ischemia. Likewise, the administration of a hemodynamically active dosing regimen of CGRP (0.03 microg/kg/min i.v.) had no effect on paced coronary flow or ischemia severity, suggesting no major role of CGRP in regulating ischemic blood flow.     

T-wave changes in patients with Wellens syndrome are associated with increased myocardial mechanical and electrical dispersion

Some patients with unstable angina and critical stenosis of the left anterior descending coronary artery (LAD) present with Wellens syndrome (WS), i.e., inverted or biphasic T-waves in the anterior precordial leads. We assessed clinical, angiographic, electro- and echocardiographic characteristic of patients with WS. In this retrospective study, clinical, angiographic, electro- and echocardiographic characteristic of 35 patients with WS were compared to 57 patients with critical LAD stenosis and normal resting electrocardiogram (ECG), and 45 subjects with normal coronary angiogram. QTc dispersion was measured from the 12-lead ECG as the difference between longest and shortest QTc intervals. Mechanical dispersion was defined as the time difference between the longest and shortest contraction durations which were measured as the time from the first deflection of the QRS complex to maximum myocardial shortening of each 18 segmental longitudinal strain curves derived by speckle tracking echocardiography. There were no significant differences in the complexity and location of the LAD lesion, anterograde and collateral flow in LAD and coronary artery dominance between patients with WS and normal ECG (P?>?0.05, for all). Patients with WS had lower global longitudinal strain (GLS) and more pronounced both QTc and myocardial mechanical dispersion than patients with critical LAD stenosis and normal ECG, and control subjects (P?<?0.05). T-wave changes in patients with WS are associated with more profound regional myocardial dysfunction and increased QTc and myocardial mechanical dispersion. Similar angiographic characteristics of the LAD lesion were seen in patients with WS and normal ECG.     

Myocardial reperfusion: leukocyte accumulation in the ischemic and remote non-ischemic regions

Neutrophil accumulation in the first hour of myocardial reperfusion was assessed in dog hearts submitted to ischemia with and without necrosis. In anesthetized dogs, the left anterior descending coronary artery was occluded for 20 min (group IS-20 n = 7) and for 90 min (group IS-90 n = 6). Immediately after reperfusion, 99m Tc-Ceretec (Exametazime-Amersham) labeled neutrophils were injected into a central vein and 60 min later the dogs were killed. The left ventricle was isolated, weighed, and sliced. Six sections, 3 from normal and 3 from reperfused regions, were divided into endocardial and epicardial layers. Myocardial and blood radiometry were used to evaluate the neutrophil accumulation during reperfusion. The differences between leukocyte accumulation in both groups were assessed comparing the ischemic/normal relations in the endocardial and epicardial layers. A second comparison considered myocardium/blood relations to allow the evaluation of differences between remote normal myocardial areas of the two experimental groups. In dogs submitted to 20 min of ischemia, leukocytes accumulated significantly more (P < 0.01) in the reperfused myocardium as compared with the non-ischemic region. The increase occurred both in the endocardial (1.49+/-0.20) and epicardial (1.48+/-0.29) regions. After 90 min ischemia, leukocyte accumulation was more intense and predominant in endocardium where there was a 4-fold (3.97+/-1.28) increase over the non-ischemic region, while in the epicardium this relation was only 2.5-fold (2.56+/-0.98). In the remote non-ischemic myocardium, leukocyte accumulation was greater in dogs submitted to 90 min of ischemia compared to the 20 min group (P < 0.01), without distinction between endocardial and epicardial layers. This accumulation in territories of non-culprit coronary arteries may be related to the blood flow abnormalities and matrix structure changes that occur in these regions during the development of an acute myocardial infarction and its natural repair.