急性心肌梗死后左室重构的动态观察

目的：观察急性心肌梗死前后心肌结构的变化，探讨心梗后左室重构变化规律。方法：16只成年健康犬麻醉后开胸结扎前降支建立心梗模型，经胸超声心动图（2．5HMz）分别于术前、术后2d、术后30d观察心脏形态，心功能及心肌应力变化。结果：术后2d出现左室扩张，收缩和舒张功能减低，心肌应力增高，左房射血力增加。术后30d较术后早期，左室进一步扩张，收缩舒张功能持续降低，心肌应力术后早期高。结论：心肌梗死后早期即出现心室扩张，收缩和舒张功能降低，心肌应力增加，心梗死左室重构贯穿整个疾病过程。     

体外心脏震波对急性心肌梗死模型猪左心室重塑的影响

背景:初期实验已经证实体外心脏震波治疗可从基因和细胞水平改善缺血心肌代谢,但是否在形态学水平也可缓解梗死后心室重塑的发展?目的:观察体外心脏震波对急性心肌梗死后左心室心功能及形态学指标的影响。方法:将25只猪随机分为3组:震波治疗组于制作心肌梗死模型后第3,5,7天,给予体外震波治疗,假震波组于制作心肌梗死模型后实施与震波治疗组相同的震波治疗操作,但不施以震波及能量,假手术组除了不造成心肌梗死,其余操作假震波组。结果与结论:与假震波组比较,震波治疗可明显缓解左室收缩末容积和舒张末容积扩大及改善左心室整体心功能(P<0.001),能显著改善心肌梗死交界区心肌局部室壁运动功能和左心室各节段运动协调性。说明及早有效的进行体外心脏震波治疗可在一定程度上延缓心肌梗死后左心室重塑由可逆阶段向不可逆阶段发展。     

Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice

Following myocardial infarction, nonischemic myocyte death results in infarct expansion, myocardial loss, and ventricular dysfunction. Here, we demonstrate that a specific proapoptotic gene, Bnip3, minimizes ventricular remodeling in the mouse, despite having no effect on early or late infarct size. We evaluated the effects of ablating Bnip3 on cardiomyocyte death, infarct size, and ventricular remodeling after surgical ischemia/reperfusion (IR) injury in mice. Immediately following IR, no significant differences were observed between Bnip3(-/-) and WT mice. However, at 2 days after IR, apoptosis was diminished in Bnip3(-/-) periinfarct and remote myocardium, and at 3 weeks after IR, Bnip3(-/-) mice exhibited preserved LV systolic performance, diminished LV dilation, and decreased ventricular sphericalization. These results suggest myocardial salvage by inhibition of apoptosis. Forced cardiac expression of Bnip3 increased cardiomyocyte apoptosis in unstressed mice, causing progressive LV dilation and diminished systolic function. Conditional Bnip3 overexpression prior to coronary ligation increased apoptosis and infarct size. These studies identify postischemic apoptosis by myocardial Bnip3 as a major determinant of ventricular remodeling in the infarcted heart, suggesting that Bnip3 may be an attractive therapeutic target.     

芪苈强心胶囊对心梗后心力衰竭大鼠periostin蛋白表达干预作用的研究

目的通过芪苈强心胶囊对心衰模型鼠Periostin蛋白表达的影响，探讨其抗心衰的作用机理。方法将通过结扎冠状动脉左前降支并饲养4周的28只心衰模型鼠随机分成4组，心衰对照组，雷米普利治疗组，芪苈强心小剂量组，芪苈强心大剂量组。同步药物干预4周后，应用酶联免疫法检测血清中血管紧张素Ⅱ（Ang Ⅱ）的浓度，应用RTPCR的方法检测梗塞区periostin mRNA。结果大剂量芪苈强心比雷米普利更有效地抑制了血清中AngⅡ水平（P〈0．05）；而小剂量芪苈强心组与雷米普利组下降水平接近，差异无显著性（P〉0．05）。Periostin的表达水平也被大剂量芪苈强心胶囊有效地抑制，与雷米普利组比较差异没有显著性（P〉0．05），明显低于小剂量组（0．53±0．06）（P〈0．05）。结论芪苈强心胶囊能够减少心梗后心衰大鼠的AngⅡ．periosfin蛋白的表达，并具有剂量依赖性。     

Revascularization of residual viable myocardium improves left ventricular dysfunction in patients after myocardial infarction.

The symptoms and prognosis of patients after myocardial infarction are essentially influenced by left ventricular function. About 50% of infarct related segments contain partly viable myocardium. The aim of this study was to test the hypothesis that regional and global left ventricular function can be improved by revascularization of infarct related segments with residual myocardial viability. In 15 of 30 consecutive patients, residual viable myocardium was found in the affected segment within 2.2 +/- 1.6 months after AMI. Myocardial viability was estimated by exercise-redistribution-reinjection thallium scintigraphy (SPECT imaging). Rest and exercise radionuclide ventriculography was performed to measure regional and global left ventricular ejection fraction before and after revascularization of the infarct related artery. 10 +/- 3 months after revascularization we observed a significant increase in the regional left ventricular ejection fraction at rest (from 32 +/- 16% to 41 +/- 19%; p = 0.03), global left ventricular ejection fraction at rest (from 38 +/- 12% to 46 +/- 11%; p = 0.01), regional LV ejection fraction during exercise (from 34 +/- 16% to 46 +/- 20%; p = 0.01), and global left ventricular ejection fraction during exercise (from 38 +/- 14% to 49 +/- 14%; p = 0.02). The results show that after revascularization of infarct related segments with residual myocardial viability, the regional and global left ventricular ejection fraction may be significantly improved, both at rest and during exercise. Thus infarct related segments should be tested for residual viability. In its presence revascularization is recommended, as the left ventricular function may be markedly improved.     

Extracellular matrix remodeling following myocardial injury

While current therapeutic strategies restore blood flow to the ischemic myocardium and limit infarct size, adverse left ventricular (LV) remodeling that progresses to dysfunction remains a significant complication following myocardial infarction (MI). The extracellular matrix (ECM) is a key component in the remodeling process, and increases in collagen occur in the infarct area to replace necrotic myocytes and form a scar. The ECM is coupled to the cell through cell surface receptors, primary of which are the integrins. In addition, the matrix metalloproteinases coordinate ECM turnover through degradation of ECM components. Several laboratories have demonstrated matrix metalloproteinase (MMP) participation in remodeling events that lead to LV dilation, and inhibition or targeted deletion of specific MMPs has beneficial effects post-MI. MMP inhibition is a particular focus of recent studies designed to understand the underlying mechanisms of LV remodeling and to evaluate pharmacologic strategies that target the ECM to affect adverse LV remodeling following MI.     

骨骼肌卫星细胞移植对心肌梗死大鼠心肌纤维化的影响

背景:现已发现心肌梗死后心肌纤维化是心室重构的重要机制,而相关干细胞心肌移植对这一过程的影响报道不多.目的:观察自体骨骼肌卫星细胞移植对心肌梗死大鼠心肌纤维化的影响,并探讨其可能机制.设计、时间及地点:随机对照动物实验,于2007-07/09在解放军第三军医大学大坪医院野战外科研究所第三研究室完成.材料:Wistar 大鼠45只,雌雄各半,体质量150～200 g,其中30只用于制备心肌梗死模型.方法:45只大鼠按随机抽签法分为3组,每组15只.心肌梗死组:结扎冠状动脉左前降支造成心肌梗死,2周后沿梗死区与正常心肌交界处多点注射0.2 mL无血清M199培养液;移植组:造模后将体外培养2周的大鼠自体卫星细胞0.2 mL以注射的方式移植到大鼠梗死区周围.假手术组:不造模,仅在左前降支周围心前壁多点注射0.2 mL生理盐水.主要观察指标:4周后测定各组大鼠缺血心肌血管内皮生长因子mRNA、血管内皮生长因子蛋白质的表达,缺血心肌毛细血管密度变化,苏木精伊红染色观察各组心肌细胞在梗死区的生长、增殖情况.结果:①卫星细胞移植4周后,假手术组和心肌梗死组血管内皮生长因子mRNA和血管内皮生长因子蛋白表达较移植组明显降低(P<0.01);心肌梗死组大鼠毛细血管密度较假手术组升高(P<0.05);移植组大鼠缺血心肌中毛细血管密度较假手术组、心肌梗死组亦明显升高(P<0.01).②苏木精-伊红染色显示假手术组大鼠心肌形态正常,结构清晰,心肌纤维排列整齐有序,肌纤维间无成纤维细胞聚集、增生现象.心肌梗死组大鼠心肌内可见成纤维细胞增生及胶原形成,心肌有序的基本结构发生紊乱.移植组大鼠其梗死区可见较多带有横纹且具有多核的肌细胞存在,组织排列较有序,纤维组织明显少于心肌梗死组.结论:卫星细胞在心肌梗死区中可增殖分化为具有弹性和收缩功能的横纹肌样细胞,并通过自分泌和旁分泌的形式分泌血管内皮生长因子促使缺血心肌毛细血管增生,从而有效地抑制了缺血心肌的纤维化进程.     

Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction

Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.     

定量组织速度成像技术评价急性心肌梗死后左室重构的左室功能

目的应用定量组织速度成像技术对心肌梗死后左室重构的左心功能进行评价,以探讨其应用价值.方法用定量组织速度成像技术测定22例健康者及临床确诊的29例心肌梗死后左室重构的冠心病患者的左室壁各节段的收缩期峰值速度(VS),舒张早期速度(VE),舒张晚期速度(VA)和VE/VA比值.测定二尖瓣口血流频谱的快速充盈速度(E),左房收缩充盈速度(A)和E/A值.容积法测左室射血分数,左室舒张末期容积指数(LVEDVI),左室收缩末期容积指数(LVESVI)及球形指数,并与正常组比较.结果心脏左室长轴方向上心梗组前壁,侧壁,下壁各节段,后间隔心尖段Vs明显下降(P＜0.01),后间隔基底段和中间段Vs无明显差异(P＞0.05);心梗组几乎各节段VE、VA、VE/VA与正常组相比有显著差异(P＜0.05).各节段平均VS与左室射血分数,球形指数等呈线性相关(r值分别为0.79,0.68,P＜0.01),舒张期功能参数平均VE/VA与二尖瓣E/A比值之间存在高度相关性(r=0.62,P＜0.01).心梗组LVEDVI和LVESVI明显增大(P＜0.01).结论定量组织速度成像可客观定位定量的反映心肌梗死局部心肌组织的收缩及舒张功能,又能体现心肌梗死后左室重构的整体功能,为心肌梗死后左室重构的心功能的评价提供了客观依据.     

Alteration in erythropoietin-induced cardioprotective signaling by postinfarct ventricular remodeling

Postinfarct remodeling impairs mechanisms of ischemic preconditioning. We examined whether myocardial response to activation of the erythropoietin (EPO) receptor is modified by postinfarct remodeling. Four weeks after induction of myocardial infarction (MI) by coronary ligation in post-MI group (post-MI) or a sham operation in sham group (sham), rat hearts were isolated and subjected to 25-min global ischemia/2-h reperfusion. Infarct size was expressed as a percentage of risk area (i.e., left ventricle) from which scarred infarct was excluded (%I/R). The heart weight was 15% larger in post-MI, but there was no intergroup difference in plasma EPO levels or myocardial EPO receptor levels. EPO infusion (5 U/ml) significantly reduced %I/R from 59.9 +/- 4.1 to 36.2 +/- 4.2 in sham and from 58.1 +/- 5.0 to 35.2 +/- 4.0 in post-MI. This EPO-induced protection was sensitive to a phosphatidylinositol 3-kinase (PI3K) inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), in sham. However, neither LY294002 nor wortmannin inhibited the EPO-induced protection in post-MI. Phosphorylation of Janus kinase 2 by EPO was attenuated and phosphorylation of Akt was not detected in post-MI. A guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one, and a mitochondrial ATP-sensitive K(+) channel (mitoK(ATP) channel) blocker, 5-hydroxydecanoate, inhibited EPO-induced protection in both sham and post-MI. Suppressor of cytokine signaling (SOCS)-1 protein level was higher by 50% in post-MI than in sham, although SOCS-3 levels were similar. These findings suggest that postinfarct remodeling disrupts cellular signaling from the EPO receptor to PI3K, presumably by increased SOCS-1. However, in the remodeled myocardium, lack of PI3K/Akt activation by the EPO receptor seems to be compensated by a mechanism upstream of the guanylyl cyclase-mitoK(ATP) channel pathway to achieve EPO-induced protection.     

组织工程化心肌片层移植心肌梗死大鼠的心功能及电生理变化

背景：组织工程化心肌组织在组成结构上类似于心脏组织的三维电偶联网络和肌肉横纹,组织样收缩功能,为病损心肌提供了修复的可能性。目的：观察心肌细胞,胶原复合体移植后心肌梗死大鼠心室肌的心功能及电生理变化。方法：将成年SD大鼠分为假手术组、模型组、移植组,后2组制作心肌梗死动物模型,胸,不结扎冠状动脉。移植组移植心肌细胞与胶原材料复合组织,其他2组不进行移植。而且具有心肌假手术组仅开结果与结论：①左室心功能：与假手术组相比,模型组左室舒张末期内径、左室收缩末期内径均显著增大（P〈0．01）,左室射血分数和左室短轴缩短率显著降低（P〈0．01）;移植组左室舒张末期内径、左室收缩末期内径、左室射血分数和左室短轴缩短率均未见明显增大或降低（P〉0．01）。②左室有效不应期变化：与假手术组相比,模型组梗死周边区有效不应期显著缩短（P〈0．01）;移植组梗死周边区有效不应期较模型组延长,差异有显著性意义（P〈0．01）。③Cx43免疫荧光结果：假手术组、模型组和移植组大鼠缝隙连接蛋白43阳性表达依次呈现阳性,弱阳性,弱阳性。但移植组缝隙连接蛋白43阳性表达高于模型组。结果可见移植的心肌细胞／胶原复合体在组织和结构上形成电偶联网络和收缩偶联,能改善心肌梗死大鼠心室肌的收缩功能及电生理特性。     

Dobutamine stress echocardiography predicts left ventricular remodeling after acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Left ventricular (LV) remodeling after acute myocardial infarction (MI) is strongly related to infarct size. The contribution of viability in the infarct zone and the presence of multivessel disease remains unknown. Because dobutamine stress echocardiography (DSE) can estimate infarct size and detect myocardial viability and multivessel disease, we postulated that DSE can accurately predict LV remodeling after acute MI. METHODS: To test this hypothesis, 30 patients age 59 +/- 15 years, 21 men, 14 with anterior MI, underwent multistage DSE (low dose, 5 to 10 microg, and peak dose) during the first week after MI occurred. Follow-up echocardiography was performed at >/=1 year. LV remodeling (2 SD increase in LV volume) occurred in 17 of 30 patients. Remodeling occurred in 12 (92%) of 13 patients with large nonviable infarct and in 1 (13%) of 8 patients with large viable infarct (P <.001). Univariate predictors of LV remodeling were baseline ejection infarct (P <.01), infarct size (number of akinetic segments at low dose P <.01), age (P <.05), and multivessel coronary disease (P <. 01). The only multivariate predictor of remodeling was infarct size. Viability of infarct zone was a negative predictor of LV remodeling. CONCLUSION: DSE performed during the first week after acute MI predicts subsequent LV remodeling. Infarct size, nonviability of the infarct zone, and age are independent predictors of LV remodeling. Myocardial viability is a strong negative predictor of LV remodeling.     

Experimental myocardial infarction: II. Acute depression and subsequent recovery of left ventricular function: serial measurements in intact conscious dogs

Acute myocardial infarction causes depression of left ventricular function, but the capacity of the ventricle to recover from such an injury remains unknown. This problem was explored by measuring left ventricular function in eight intact conscious dogs before, 1 hr after, and again 6-8 days after myocardial infarction. Acute myocardial infarction was produced using a technique which entails gradual inflation over an average period of 1 hr of a balloon cuff previously implanted around the left anterior descending coronary artery. Occurrence of anterior wall infarction was detected electrocardiographically and later confirmed by postmortem examination. Left ventricular function was evaluated from the relationship between left ventricular developed pressure (left ventricular peak systolic pressure minus left ventricular end-diastolic pressure) and left ventricular end-diastolic pressure during transient aortic occlusion with a balloon catheter. Left ventricular function curves were obtained by plotting left ventricular-developed pressure at increasing left ventricular end-diastolic pressures up to 50 mm Hg. Acute myocardial infarction caused marked depression of left ventricular function measured 1 hr after onset of infarction, but 1 wk later all eight animals showed improvement with return of function toward the control levels. A small but significant descending limb was noted at left ventricular end-diastolic pressures above 35 mm Hg. Quantitatively, the descending limb was similar before, 1 hr after, and 1 wk after myocardial infarction. Hemodynamic data revealed evidence of left ventricular failure in all animals, but variability in individual hemodynamic parameters was noted. The data indicate that the marked depression of left ventricular function observed immediately after experimental acute myocardial infarction undergoes considerable resolution within 1 wk, but that functional recovery remains incomplete.     

急性心梗后心肌组织特征与早期再灌注和预后的关系

目的⑶评价急性心肌梗塞患者心肌超声组织特征变化趋势与预后的关系以及早期再灌注对心肌组织密度的影响⒚方法⑶我们分析了首次发病的 ６９ 例 Ｑ 波急性心肌梗塞患者入院后 ２４ 小时内、７２ 小时、２ 周、３ 个月和６ 个月的心肌灰阶⒚根据患者有无早期再灌注分为⑶无早期再灌注组 ４６ 例⒙早期再灌注组 １６ 例和死亡组 ７ 例⒚结果⑶在无早期早再灌注组⒙梗塞区心肌灰阶的均值、离散度于入院 ３ 个月后明显高于入院时 ⒉ Ｐ＜ ００ ５⒕⒚早期再灌注组梗塞区心肌灰阶的均值、离散度在入院 ２ 周即开始逐渐下降 ⒉ Ｐ＜ ００５⒕⒚死亡组梗塞区的心肌灰阶值在入院 ７２ 小时后即明显增加 ⒉ Ｐ＜ ００ ５⒕⒚结论⑶以超声组织定征视频法测定的心肌灰阶指标反映了心梗后心室重构过程中心肌组织结构的动态改变⒙并发现早期再灌注使梗塞区组织密度和非梗塞区心室重构减轻⒚     

超声心动图评价犬急性心肌梗死早期左心室重构的实验研究

目的 采用超声心动图检测犬急性心肌梗死(AMI)后左心室重构发生时间及6 h内左心室重构变化.方法 对14只健康成年犬麻醉后开胸结扎左冠状动脉左前降支制备AMI模型,成功制备8只AMI模型,超声心动图分别于术前,术后1、2、3、4、5及6 h观察梗死心肌室壁厚度(WIT)、室壁运动积分指数(WMSI)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、左心室射血分数(LVEF).检查结束后处死实验犬,取梗死区心肌组织行病理学检查.结果 与术前比较,术后1 h实验犬WMSI、LVESV(P<0.01)和LVEDV(P<0.05)增大,LVEF和WIT减小(P<0.01);WMSI术后3、4、5、6 h高于术后1 h(P<0.05);术后4、5、6 h和术后2 h比较,LVEDV和LVESV增高,LVEF降低.病理检查显示:梗死区心肌细胞发生肿胀,肌浆呈颗粒状凝集而分布不均,出现核固缩.结论 犬AMI后1 h即可出现左心室重构,超声心动图可评估AMI后早期左心室重构.     

Artemisinin attenuates post-infarct myocardial remodeling by down-regulating the NF-κB pathway

Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.     

Remodeling after acute myocardial infarction: mapping ventricular dilatation using three dimensional CMR image registration

Background

Progressive heart failure due to remodeling is a major cause of morbidity and mortality following myocardial infarction. Conventional clinical imaging measures global volume changes, and currently there is no means of assessing regional myocardial dilatation in relation to ischemic burden. Here we use 3D co-registration of Cardiovascular Magnetic Resonance (CMR) images to assess the long-term effects of ischemia-reperfusion injury on left ventricular structure after acute ST-elevation myocardial infarction (STEMI).

Methods

Forty six patients (age range 33–77 years) underwent CMR imaging within 7 days following primary percutaneous coronary intervention (PPCI) for acute STEMI with follow-up at one year. Functional cine imaging and Late Gadolinium Enhancement (LGE) were segmented and co-registered. Local left ventricular wall dilatation was assessed by using intensity-based similarities to track the structural changes in the heart between baseline and follow-up. Results are expressed as means, standard errors and 95% confidence interval (CI) of the difference.

Results

Local left ventricular remodeling within infarcted myocardium was greater than in non-infarcted myocardium (1.6% ± 1.0 vs 0.3% ± 0.9, 95% CI: -2.4% – -0.2%, P = 0.02). One-way ANOVA revealed that transmural infarct thickness had a significant effect on the degree of local remodeling at one year (P < 0.0001) with greatest wall dilatation observed when infarct transmurality exceeded 50%. Infarct remodeling was more severe when microvascular obstruction (MVO) was present (3.8% ± 1.3 vs −1.6% ± 1.4, 95% CI: -9.1% – -1.5%, P = 0.007) and when end-diastolic volume had increased by >20% (4.8% ± 1.4 vs −0.15% ± 1.2, 95% CI: -8.9% – -0.9%, P = 0.017).

Conclusions

The severity of ischemic injury has a significant effect on local ventricular wall remodeling with only modest dilatation observed within non-ischemic myocardium. Limitation of chronic remodeling may therefore depend on therapies directed at modulating ischemia-reperfusion injury. CMR co-registration has potential for assessing dynamic changes in ventricular structure in relation to therapeutic interventions.     

磁共振成像对急性心肌梗死后再灌注损伤和左室重构的评估

背景磁共振成像对急性心肌梗死的研究多注重心肌灌注改变. 目的分析比较MRI征象中梗死和再灌注心肌的特征,并与病理切片染色结果进行对比. 设计完全随机分组设计,随机对照实验. 单位解放军空军总医院磁共振科,解放军总医院放射科. 材料实验于2003-10/12在解放军总医院动物实验中心完成.选用14只中国小型猪,随机分2组,每组7只,分别为梗死组和再灌注组.分别制成单纯心肌梗死和心肌梗死再灌注动物模型.术前和手术后1个月内多次进行MRI平扫、增强扫描检查.术后1个月取与MRI对应层面及厚度的心脏标本做病理大切片,进行氯化三苯基四氮唑蓝染色检查,对应氯化三苯基四氮唑蓝染色结果分别取梗死心肌(相当于左室前壁)和正常心肌(相当于左室后壁)及其相邻部标本进行苏木精-伊红染色检查观察梗死心肌范围. 主要观察指标两组猪心肌T1和T2弛豫时间改变;梗死和正常心肌的形态改变. 结果纳入中国小型猪14只,梗死组和再灌注组各7只,在造模过程中梗死组死亡1只,进入结果分析猪13只,梗死组6只,再灌注组7只.①T1,T2弛豫时间数值梗死组梗死区心肌明显大于正常心肌[(1159.54±78.67),(60.15±6.31)ms,(1056.15±70.95),(47.46±7.94)ms,t=2.63,5.38,P＜0.05,0.01];再灌注组梗死区心肌也明显大于正常心肌[(1171.14±139.98),(56.64±6.16)ms,(1074.64±97.61),(44.57±4.25)ms,t=2.64,6.24,P＜0.05,0.01].②单纯梗死心肌与再灌注梗死心肌在MRI上均有明显强化,但两者弛豫时间和增强特征无明显差别,单纯梗死比再灌注梗死组左室扩大明显.③MRI所见与病理检查结果相对照表明病理切片氯化三苯基四氮唑蓝染色所示梗死区与MRI所见一致. 结论①MRI对心肌梗死以及左室重构评价有价值,MRI和增强扫描不能鉴别梗死和不可逆性再灌注心肌缺血区心肌组织.②再灌注对急性心肌梗死后左室重构改变有治疗作用.③MRI与病理检查具有良好的相关性.     

No-reflow phenomenon: maintaining vascular integrity

The no-reflow phenomenon relates to the inability to reperfuse regions of the myocardium after ischemia, despite removal of the large epicardial coronary artery occlusion. The mechanism involves microvascular obstruction. In experimental studies, using markers for flow (thioflavin S, carbon black, microspheres), perfusion defects associated with no-reflow demonstrated ultrastructural evidence of localized endothelial swelling and blebs that appeared to obstruct flow. In humans no-reflow is more complicated due to the microemboli of atherosclerotic debris and thrombi generated by percutaneous coronary intervention. The no-reflow zone expands during the first few hours of reperfusion suggesting an element of reperfusion injury. In animal models, extensive no-reflow was associated with worse infarct expansion. The phenomenon of no-reflow following reperfusion therapy for myocardial infarction in humans has been demonstrated by magnetic resonance imaging, echo contrast agents, thallium, technecium-99m-labeled albumin microspheres, Thrombolysis In Myocardial Infarction (TIMI) scores, and myocardial blush grade. Patients exhibiting no-reflow following reperfusion therapy for myocardial infarction have greater left ventricular dilation and remodeling, more congestive heart failure, shock, and reduced survival. Certain vasodilators (adenosine, nitroprusside, nicorandil, and calcium blockers) are used acutely in the catheterization laboratory and appear to improve no-reflow, but systematic studies on therapy for no-reflow are needed. There is now clinical evidence that no-reflow is a strong predictor of long-term mortality that is independent of and beyond that provided by infarct size. Identifying and treating no-reflow may have important benefits including enhancing delivery of nutrients and cells required for healing and reducing infarct expansion and ventricular remodeling, which ultimately may reduce congestive heart failure and mortality.     

The effects of different initiation time of exercise training on left ventricular remodeling and cardiopulmonary rehabilitation in patients with left ventricular dysfunction after myocardial infarction

Purpose: The purpose of this study was to determine whether different initiation of exercise training (ET) produces different effect sizes for left ventricular (LV) remodeling and cardiopulmonary rehabilitation in patients with LV dysfunction after myocardial infarction (MI). Method: Trials evaluating ET outcomes identified by searches in OVID MEDLINE, EMBASE, PubMed and WEB OF SCIENCE were used. Meta-analysis was conducted with the use of the software STATA 11.0. The results were expressed as the standardized mean difference (SMD), with corresponding 95% CI and p value. Results: The largest changes in LV remodeling and cardiopulmonary capacity rehabilitation were obtained when programs began the acute phase after MI. With the healing of MI, the beneficial effects of ET on LV ejection fraction (LVEF), LV end-systolic diameter (LVDs) and peak VO₂ were gradually weakened even worse. The incidence of major adverse cardiac events was not significantly increased in acute phase post-MI. Sensitivity analyses show that ET still had significant effect in reducing LVDs and increasing peak VO₂, while ET no longer had statistical effect in increasing LVEF but showed favorable trends when the same research institution's works were excluded. Conclusions: ET has favorable effects on LV remodeling and cardiopulmonary rehabilitation in LV dysfunction post-MI patients. The greatest benefits are obtained when ET starts at the acute phase following MI.

• Implications for Rehabilitation

• Early exercise training is safe and feasible in acute and healing phase after myocardial infarction.

• Early exercise training could attenuate LV remodeling and improve cardiopulmonary capacity in patients with myocardial infarction after hospital discharge (around one week post-MI).

• Exercise training has favorable effects on LV remodeling and cardiopulmonary capacity rehabilitation. Exercise training should be treated to have the same roles with drugs in secondary prevention of myocardial infarction.