瑞舒伐他汀对兔心肌梗死后心室重构及细胞凋亡的影响

目的：观察瑞舒伐他汀对新西兰大白兔心肌梗死后左室重构及心肌细胞凋亡的影响。方法：45只雄性新西兰大白兔随机分成三组,即：假手术组（S,n=15）,心肌梗死对照组（MI,n=15）,心肌梗死瑞舒伐他汀干预组（R,n=15）。MI组和R组大鼠结扎左冠状动脉前降支建立AMI模型。心肌梗死对照组及假手术组术后24h灌等量的生理盐水．．瑞舒伐他汀干预组于术后24h直接灌胃法给药,给药剂量以10mg／kgtd计算。干预2周后,进行心脏超声测定,随即处死新西兰大白兔、取出心脏,观察病理组织形态,并通过Westernblot方法检测Bcl-2,Bax在心肌梗死边缘区的蛋白表达。结果：①心脏超声检测表明干预组左室舒张末内径（LVEDD）、左室收缩末内径（LVESD）较心肌梗死对照组降低而左室射血分数（LVEF）较心肌梗死对照组增高。②干预组心肌梗死边缘区Bax表达与心肌梗死对照组比较未见统计学差异,而Bcl一2表达高于心肌梗死对照组。结论：瑞舒伐他汀上调Bcl一2的表达,改善心室重构。     

瑞舒伐他汀强化治疗对急性ST段抬高型心肌梗死患者PCI手术预后的影响

目的:探讨瑞舒伐他汀强化治疗对急性ST段抬高型心肌梗死(STEMI)患者PCI术预后的影响。方法:选择2013年6月-2015年6月我院收治的STEMI患者90例,随机分为研究组与对照组,每组各45例。研究组患者PCI术前及术后均给予瑞舒伐他汀强化治疗,对照组仅在术后给予瑞舒伐他汀治疗。观察并比较两组患者术中慢血流及无复流的发生率,TNI、CK-MB、NT-pro BNP及hs-CRP水平变化,以及左室舒张末期内径、左心房内径、左室射血分数、室间隔厚度。结果:研究组术中慢血流及无复流的发生率显著低于对照组(P0.05);两组患者治疗后TNI、CK-MB、NT-pro BNP、hs-CRP水平均低于治疗前,且研究组低于对照组,差异具有统计学意义(P0.05);两组治疗后左室舒张末期内径、左心房内径、左室射血分数、室间隔厚度比较,差异无统计学意义(P0.05)。结论:瑞舒伐他汀强化治疗可以有效降低STEMI患者心肌坏死及炎症反应的发生率,改善心室重构,值得临床推广应用。     

瑞舒伐他汀预处理对心肌缺血再灌注损伤大鼠自噬和凋亡的影响及机制研究

目的:探讨瑞舒伐他汀预处理对心肌缺血再灌注损伤(MIRI)大鼠自噬因子和凋亡相关基因的影响及作用机制。方法:将60只SD级大鼠纳入研究,遵循随机数字表法分成假手术组、模型组以及预处理组,每组20只。模型组以及预处理组大鼠均制备MIRI模型,假手术组按照相同的方式开胸,仅穿线不进行冠状动脉的结扎。模型制备前7d,预处理组予以瑞舒伐他汀20 mg/(kg·d)灌胃处理,假手术组以及模型组大鼠则予以生理盐水5 m L/d处理。比较三组大鼠心肌组织凋亡率、心肌梗死面积、左心室血流动力学参数、自噬因子P62、Beclin-1蛋白表达水平以及凋亡相关基因Bcl-2、Bax、Cyt C蛋白表达水平。结果:预处理组及模型组大鼠的心肌组织凋亡率以及心肌梗死面积均高于假手术组,但预处理组低于模型组(均P<0.05)。预处理组及模型组大鼠的左心室舒张末压(LVEDP)均高于假手术组,但预处理组低于模型组(均P<0.05);预处理组及模型组大鼠的左心室内压最大上升速率(+dp/dtmax)、左心室内压最大下降速率(-dp/dtmax)低于假手术组,但预处理组高于模型组(均P<0.05)。预处理组及模型组大鼠的P62、Beclin-1蛋白表达水平均高于假手术组,但预处理组低于模型组(均P<0.05)。预处理组及模型组大鼠Bcl-2 m RNA表达水平低于假手术组,但预处理组高于模型组(均P<0.05);预处理组及模型组大鼠Bax m RNA表达水平及Cyt C蛋白表达水平高于假手术组,但预处理组低于模型组(均P<0.05)。结论:瑞舒伐他汀预处理可显著减轻MIRI大鼠心肌组织受损程度,其主要作用机制可能与瑞舒伐他汀有效抑制心肌细胞自噬因子表达以及调控凋亡相关基因表达有关。     

通心络胶囊对心肌梗死模型大鼠MMP-2和TIMP-1表达的影响

目的:探讨通心络胶囊对心肌梗死大鼠基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶抑制剂1(TIMP-1)的表达、心脏结构和功能改变的影响.方法:取SD大鼠24只,随机分成假手术组(SH group,n=8),心肌梗死模型组(MI group,n=8),用药组(Treated group,n=8).术后4w,测量左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室上升最大速率(+dP/dtmax)、左室下降最大速率(-dP/dtmax);测定全心重(THW)及左心室称重(LVW),计算THW/体重(BW)、LVW/BW值和心肌梗死面积;用酶联免疫吸附法(ELISA)检测血清MMP-2及TIMP-1水平.结果:与SH组比较,MI组心室重量增加,心室功能显著降低,MMP-2升高,TIMP-1降低;与MI组比较,Treated组心室重量降低,心室功能显著增高,MMP-2减少,TIMP-1增加.结论:大鼠心肌梗死后,通心络胶囊能降低血清MMP-2水平,升高TIMP-1水平,抑制左室重构、改善心功能.     

负荷量阿托伐他汀对稳定型冠心病患者非心脏手术围手术期保护作用的研究

目的:探讨负荷量阿托伐他汀对稳定型冠心病患者非心脏的择期外科手术围手术期主要不良心脏事件的保护作用。方法:将拟行非心脏外科手术的60名稳定型冠心病患者随机分为负荷量阿托伐他汀组(n=30)和对照组(n=30),其中负荷量阿托伐他汀治疗组在术前12小时给予阿托伐他汀80 mg顿服,术前2小时阿托伐他汀40 mg顿服,且每晚服用阿托伐他汀40 mg,对照组术前每晚服用阿托伐他汀20 mg,而后进行非心脏的外科手术(主要病种为慢性胆囊结石胆囊炎、慢性阑尾炎、消化性溃疡、疝气),术后负荷量组给予每晚服用阿托伐他汀40 mg,对照组每晚服用阿托伐他汀20 mg。比较两组围手术期主要不良心脏事件(包括心脏性猝死,急性心肌梗死,非计划性血运重建)的发生情况。结果:对照组出现1例急性前壁ST段抬高型心肌梗死并行急诊前降支介入再灌注治疗和7例无症状型心肌梗死,负荷量阿托伐他汀组出现1例无症状型心肌梗死,围手术期心肌梗死发生率较对照组明显降低(P0.05)。结论:负荷量阿托伐他汀可显著降低稳定型冠心病患者非心脏的择期外科手术围手术期主要不良心脏事件如心肌梗死,特别是无症状型心肌梗死的发生率,但该结果尚需大样本多中心随机对照临床试验进一步证实。     

瑞舒伐他汀治疗慢性心力衰竭80例疗效观察

目的：评价瑞舒伐他汀治疗慢性心力衰竭的疗效。方法：选取2009年6月-2010年9月住院的心力衰竭患者80例,随机分为瑞舒伐他汀治疗组和对照组,对照组采用常规内科治疗。瑞舒伐他汀治疗组在常规内科治疗的基础上加用瑞舒伐他汀治疗。观察两组患者左心室舒张末期内径（LVEDD）,左心室射血分数（LVEF及临床疗效。结果：两组治疗前LVEDD及LVEF水平比较无差异（P〉0.05）,治疗后两组LVEDD水平明显下降,LVEF水平明显升高（P〈0.05）,瑞舒伐他汀治疗后LVEDD及LVEF水平改善均明显优于对照组（P〈0.05）。瑞舒伐他汀组临床疗效高于对照组（P〈0.05）。结论：瑞舒伐他汀可以改善慢性心力衰竭患者的心脏功能。     

瑞舒伐他汀对载脂蛋白E 基因敲除小鼠动脉粥样硬化中 调节性T 细胞的影响

目的:探讨瑞舒伐他汀对载脂蛋白E基因敲除(ApoEKO)小鼠动脉粥样硬化中调节性T细胞的影响。方法:首先将30只ApoEKO小鼠建立动脉粥样硬化模型,随机分为高胆固醇饮食组(对照组)、瑞舒伐他汀低剂量组和瑞舒伐他汀高剂量组,各组分别给予蒸馏水或瑞舒伐他汀进行干预8周;将主动脉根部行冰冻切片油红染色,评估粥样硬化斑块面积大小;免疫组织化学法检测主动脉根部粥样硬化斑块处调节性T细胞(Treg)的表达。结果:各组小鼠均有动脉粥样硬化斑块形成,采用瑞舒伐他汀治疗的小鼠动脉粥样硬化斑块的面积明显小于未经治疗的小鼠(P<0.01),同时瑞舒伐他汀能明显增加粥样硬化病变处调节性T细胞的表达,且呈现剂效关系。结论:本实验观察到瑞舒伐他汀不仅能减小ApoEKO小鼠的主动脉粥样硬化斑块,且能使调节性T细胞的表达增多,推测瑞舒伐他汀可以通过促进调节性T细胞的生成而起到抑制动脉粥样硬化的作用。     

Ghrelin对心肌梗死后心肌重塑及心脏功能的影响及其机制研究

目的:观察ghrelin对心肌梗死(MI)大鼠心肌重塑和心脏功能的影响,并探讨其可能的机制。方法:应用冠状动脉结扎术创建大鼠MI模型,并设立假手术组作为对照;造模成功后每天2次注射ghrelin(100μg/kg),持续4周,以此作为MI-ghrelin组,并以每天注射生理盐水的MI大鼠作为MI-生理盐水组。检测和比较各组大鼠左心室重塑和血流动力学的改变情况;非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶(MMP)-2、MMP-9 mRNA和蛋白的表达;梗死边界心肌细胞的凋亡情况。结果:Ghrelin可使心肌梗死后的MI大鼠降低的缩短分数(FS)、左室内压最大变化率均显著下降(dP/dtmax)、疤痕厚度明显升高,增加左室舒张末压(LVEDP)、左室收缩末内径(LVESD)、左室舒张末期内径(LVEDD)、梗死边界心肌细胞的凋亡指数显著降低。此外,ghrelin可抑制心肌梗死后的MI大鼠非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、质金属蛋白酶(MMP)-2和MMP-9的mRNA和蛋白的表达。结论:Ghrelin可缓解MI后大鼠LV功能紊乱及心室重塑,这可能与其抑制炎症反应及基质金属蛋白酶的表达有关。     

阿托伐他汀预处理对心肌缺血再灌注损伤大鼠心室重构、炎症反应和氧化应激的影响

目的:研究阿托伐他汀预处理对心肌缺血再灌注损伤大鼠心室重构、炎症反应和氧化应激的影响。方法:选取90只SD级大鼠进行研究,将其随机分成假手术组、缺血再灌注组、阿托伐他汀组,每组30只。假手术组与缺血再灌注组大鼠予以生理盐水(5 m L/d)连续灌胃7d处理,阿托伐他汀组予以阿托伐他汀20 mg/(kg·d)连续灌胃7 d,上述干预结束后,缺血再灌注组与阿托伐他汀组大鼠通过阻断大鼠冠状动脉左前降支的方式建立心肌缺血再灌注损伤模型。比较三组大鼠心室重构指标水平、炎症反应以及氧化应激相关指标水平。结果:缺血再灌注组、阿托伐他汀组大鼠的左室相对重量、右室相对重量、室间隔厚度、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、丙二醛(MDA)、乳酸脱氧酶(LDH)水平均高于假手术组,且阿托伐他汀组大鼠上述指标均低于缺血再灌注组(均P<0.05);缺血再灌注组、阿托伐他汀组大鼠白介素-10(IL-10)、超氧化物气化酶(SOD)水平低于假手术组,且阿托伐他汀组大鼠IL-10、SOD水平高于缺血再灌注组(均P<0.05)。结论:阿托伐他汀预处理可有效预防心肌缺血再灌注损伤大鼠心室重构,同时可在一定程度上改善大鼠的炎症反应和氧化应激反应。     

瑞舒伐他汀促进缺氧复氧间充质干细胞增殖的机制研究

目的:探讨瑞舒伐他汀对缺氧复氧损伤后脂肪来源间充质干细胞增殖的影响及机制。方法:酶消化法分离小鼠的脂肪间充质干细胞(AD-MSCs),流式细胞术检测CD90、CD44、CD34、CD45等细胞标志物。建立缺氧(H)6h/复氧(R)42h细胞模型,AD-MSCs分为3组:①对照组;②缺氧/复氧组(H/R);③H/R+瑞舒伐他汀干预组(浓度分别为10-8、10-7、10-6mol/L)。MTT法测定各组细胞增殖,免疫印迹法检测细胞内Akt、Erk及其磷酸化的表达水平。结果:流式细胞术结果显示脂肪间充质干细胞CD44及CD90阳性,CD34、CD45阴性。MTT实验显示在缺氧环境中,瑞舒伐他汀的干预可显著增加AD-MSCs的增殖(P<0.05)。Westernblot检测pAkt及pErk的表达在瑞舒伐他汀干预组明显高于对照组和H/R组。(P<0.05)。结论:瑞舒伐他汀可通过Akt、Erk信号途径促进H/R损伤后AD-MSCs的增殖。     

Heterogeneity in MT1-MMP activity with ischemia-reperfusion and previous myocardial infarction: relation to regional myocardial function

After a myocardial infarction (MI), an episode of ischemia-reperfusion (I/R) can result in a greater impairment of left ventricular (LV) regional function (LVRF) than that caused by an initial I/R episode in the absence of MI. Membrane type-I matrix metalloproteinase (MT1-MMP) proteolytically processes the myocardial matrix and is upregulated in LV failure. This study tested the central hypothesis that a differential induction of MT1-MMP occurs and is related to LVRF after I/R in the context of a previous MI. Pigs with a previous MI [3 wk postligation of the left circumflex artery (LCx)] or no MI were randomized to undergo I/R [60-min/120-min left anterior descending coronary artery (LAD) occlusion] or no I/R as follows: no MI and no I/R (n = 6), no MI and I/R (n = 8), MI and no I/R (n = 8), and MI and I/R (n = 8). Baseline LVRF (regional stroke work, sonomicrometry) was lower in the LAD region in the MI group compared with no MI (103 ± 12 vs. 188 ± 26 mmHg·mm, P < 0.05) and remained lower with peak ischemia (35 ± 8 vs. 88 ± 17 mmHg·mm, P < 0.05). Using a novel interstitial microdialysis method, MT1-MMP was directly measured and was over threefold higher in the LCx region and over twofold higher in the LAD region in the MI group compared with the no MI group at baseline. MT1-MMP fluorogenic activity was persistently elevated in the LCx region in the MI and I/R group but remained unchanged in the LAD region. In contrast, no changes in MT1-MMP occurred in the LCx region in the no MI and I/R group but increased in the LAD region. MT1-MMP mRNA was increased by over threefold in the MI region in the MI and I/R group. In conclusion, these findings demonstrate that a heterogeneous response in MT1-MMP activity likely contributes to regional dysfunction with I/R and that a subsequent episode of I/R activates a proteolytic cascade within the MI region that may contribute to a continued adverse remodeling process.     

瑞舒伐他汀治疗颈动脉粥样硬化斑块的临床研究

目的:研究瑞舒伐他汀对颈动脉粥样硬化斑块的治疗效果。方法:将在本院接受治疗的250例颈动脉粥样硬化斑块患者随机分成治疗组125例和对照组125例,治疗组服用瑞舒伐他汀10mg/晚,对照组行其他非瑞舒伐他汀药物治疗,进行为期6个月的观察对比。结果:治疗组治疗后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)水平显著下降,高密度脂蛋白(HDL)水平显著升高(P<0.05),颈动脉内膜-中层厚度(IMT)、斑块面积变小,与治疗前比较,差异有统计学意义(P<0.05);对照组治疗前后无显著性差异(P>0.05)。结论:瑞舒伐他汀对降低血脂、减缓不稳定型心绞痛早期动脉粥样硬化、稳定斑块和预防脑血管疾病起到非常重要的作用。     

Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x 10(5) cells in 20 microl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 +/- 2% vs. 36 +/- 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 +/- 3% vs. 16 +/- 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 +/- 0.3% of injected cells) expressed von Willebrand factor (16.9 +/- 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.     

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 30 healthy volunteers were randomized in a double-blind fashion to receive oral rosuvastatin (20 mg/day) and placebo, rosuvastatin, and celecoxib (100 mg bid) or placebo alone, all for 21 days. Twenty-four hours after the final administration of study medication, FMD was measured before and after IR. Pre-IR FMD was similar between groups in both protocols. In the acute administration protocol, rosuvastatin significantly prevented the blunting of FMD associated with IR (FMD pre-IR: 8.4 ± 1.3%; post-IR: 6.2 ± 1.3%; P = 0.01 ANOVA, treatment group interaction). In the daily administration protocol, IR significantly blunted FMD in the placebo group (FMD pre-IR: 7.5 ± 0.9%; post-IR: 3.3 ± 0.7%; P < 0.001). Chronic treatment with rosuvastatin did not modify this ischemic injury (FMD pre-IR: 6.9 ± 0.4%; post-IR: 1.6 ± 1.0%; P < 0.001; P = NS ANOVA, treatment group interaction). Similarly, FMD responses post-IR in volunteers receiving rosuvastatin and celecoxib did not significantly differ from placebo (FMD pre-IR: 8.3 ± 0.9%; post-IR: 2.1 ± 0.8%; P < 0.001; P = NS ANOVA, treatment group interaction). In contrast to acute administration, chronic rosuvastatin does not prevent the development of IR-induced endothelial dysfunction in normal humans.     

川芎嗪联用L-精氨酸对缺血/再灌注损伤兔心肌线粒体功能的影响

探讨川芎嗪联用L-精氨酸对心肌缺血／再灌注损伤（MI／RI）时心肌细胞线粒体功能的影响。方法：选用日本大耳白兔50只,随机分为正常对照组（A组）、心肌缺血／再灌注组（B组）、心肌缺血／再灌注＋川芎嗪治疗组（C组）、心肌缺血／再灌注＋L-精氨酸治疗组（D组）和心肌缺血／再灌注＋川芎嗪＋L-精氨酸治疗组（E组）。观察心肌线粒体呼吸功能、Ca^2＋浓度（[Ca^2＋]m）、丙二醛浓度（MDA）、超氧化物歧化酶活性（SOD）和心肌组织三磷酸腺苷（ATP）、能荷（EC）的变化。结果：C、D、E组与B组比较,线粒体呼吸控制率（RCR）、Ⅲ态呼吸速率（ST3）、SOD明显升高,Ⅳ态呼吸速率（ST4）、[Ca^2＋]m、MDA显著降低,心肌组织ATP、EC均明显增高;且与A组比较,E组上述指标均无明显差异。结论：川芎嗪联用L-精氨酸可通过降低氧自由基水平和减轻钙超载,而改善缺血／再灌注损伤心肌的线粒体功能。     

Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion

OBJECTIVE: To study the effects of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further determine the role of insulin in the GIK-induced cardioprotective effect in vivo . METHODS: Forty eight male rabbits were subjected to 40 min MI followed by R for 3 h and were randomly received one of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1), beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood glucose, electrolytes, arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL analysis) were determined in a blinded manner. RESULTS: MI/R caused significant cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/- 2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle, n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery of cardiac systolic/diastolic function at the end of R. Treatment with insulin alone decreased blood glucose significantly but still exerted cardioprotective effects comparable with that of GIK. CONCLUSIONS: GIK exerts cardioprotective effects against postischemic myocardial injury and improves cardiac functional recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key role in the GIK-elicited myocardial protection in MI/R.     

鬼笔环肽对心肌梗死大鼠离体心脏牵张所致电生理学改变的影响

本文旨在探讨肌动蛋白稳定剂--鬼笔环肽(phalloidin)对心肌梗死(myocardial infarction,MI)大鼠离体心脏牵张所致电生理学改变的影响.将32只Wistar大鼠随机分为正常对照组(n=9)、鬼笔环肽组(n=7)、MI组(n=9)、MI 鬼笔环肽组(n=7).离体心脏经Langendorff灌流后,通过改变水囊容积,以△V=0.1、0.2、0.3 mL对心室牵张5 S,观察牵张后效应30 s,记录左心室内压力变化[左心室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张末压(left ventricular end-diastolic pressure,LVEDP)、室内压最大上升,下降速率(±dp/dt max)]、单相动作电位复极90%的时程(monophasic action po-tential duration at 90%repolarization,MAPD 90)、室性期前收缩(premature ventricular beats,PVB)及室性心动过速(ventriculartachycardia,VT)发生率.结果显示,牵张使正常对照组及MI组大鼠MAPD 90明显延长(P<0.05,P<0.01),MI组大鼠MAPD 90延长更显著(P<0.05,P<0.01).鬼笔环肽(1 μmol/L)对正常及MI心肌基础状态下的MAPD 90无影响,但使MI心肌牵张后已延长的MAPD90缩短(△V=0.3 mL时,P<0.05).牵张后MI组大鼠PVB、VT的发生率明显高于正常对照组(均P<0.01).鬼笔环肽对正常大鼠心肌牵张后PVB、VT的发生率无显著影响,但使MI心肌PVB、VT的发生率明显下降(均P<0.01).MI组大鼠LVSP及 ap/dt max 较正常对照组显著降低(P<0.01);鬼笔环肽可使MI心肌LVSP轻度回升,但无统计学意义.结果表明,MI后牵张加重恶性心律失常的发生和持续,鬼笔环肽可以明显抑制其发生.     

Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion

This study compared the effects of rosuvastatin on left ventricular infarct size in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24 h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide synthase (NOS) expression, and mobilize progenitor stem cells after ischemic injury. Mice received blinded and randomized administration of rosuvastatin (20 mg.kg(-1).day(-1)) or saline from 2 days before surgery until death. After 60 min of ischemia with reperfusion, infarct size was reduced by 18% (P = 0.03) in mice randomized to receive rosuvastatin (n = 18) vs. saline (n = 22) but was similar after permanent occlusion in rosuvastatin (n = 17) and saline (n = 20) groups (P = not significant). Myocardial infarct size after permanent left anterior descending coronary artery occlusion (n = 6) tended to be greater in NOS3-deficient mice than in the wild-type saline group (33 +/- 4 vs. 23 +/- 2%, P = 0.08). Infarct size in NOS3-deficient mice was not modified by treatment with rosuvastatin (34 +/- 5%, n = 6, P = not significant vs. NOS3-deficient saline group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar in rosuvastatin and saline groups as was the percentage of CD34(+), Sca-1(+), and c-Kit(+) cells. Left ventricular NOS3 mRNA and protein levels were unchanged by rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia-reperfusion but not after permanent coronary occlusion, suggesting a potential anti-inflammatory effect. Although we were unable to demonstrate that the myocardial protection was due to an effect on neutrophil infiltration, stem cell mobilization, or induction of NOS3, these data suggest that rosuvastatin may be particularly beneficial in myocardial protection after ischemia-reperfusion injury.     

Serial magnetic resonance imaging based assessment of the early effects of an ACE inhibitor on postinfarction left ventricular remodeling in rats

In vivo assessment of treatment efficacy on postinfarct left ventricular (LV) remodeling is crucial for experimental studies. We examined the technical feasibility of serial magnetic resonance imaging (MRI) for monitoring early postinfarct remodeling in rats. MRI studies were performed with a 7-Tesla unit, 1, 3, 8, 15, and 30 days after myocardial infarction (MI) or sham operation, to measure LV mass, volume, and the ejection fraction (EF). Three groups of animals were analyzed: sham-operated rats (n = 6), MI rats receiving lisinopril (n = 11), and MI rats receiving placebo (n = 8). LV dilation occurred on day 3 in both MI groups. LV end-systolic and end-diastolic volumes were significantly lower in lisinopril-treated rats than in placebo-treated rats at days 15 and 30. EF was lower in both MI groups than in the sham group at all time points, and did not differ between the MI groups during follow-up. Less LV hypertrophy was observed in rats receiving lisinopril than in rats receiving placebo at days 15 and 30. We found acceptable within- and between-observer agreement and an excellent correlation between MRI and ex vivo LV mass (r = 0.96; p < 0.001). We demonstrated the ability of MRI to detect the early beneficial impact of angiotensin-converting enzyme (ACE) inhibitors on LV remodeling. Accurate and noninvasive, MRI is the tool of choice to document response to treatment targeting postinfarction LV remodeling in rats.