大鼠慢性心肌梗死模型的制作

目的:建立可操作性强的大鼠慢性心肌梗死模型制作方法。方法:健康雄性SD大鼠40只采取开胸术式结扎冠状动脉前降支,观察结扎远端心肌颜色的改变和心电图变化确定是否梗死。结果:所有大鼠出现明确的梗死改变,心电图J点抬高,可出现Q波。早期死亡率为15%,总死亡率为22.5%。结论:准确结扎前降支才能保证造模成功,加强呼吸道管理是提高手术后大鼠成活率的重要措施。     

实验性心力衰竭大鼠模型的建立及评价

目的建立实验性心力衰竭大鼠模型,并对其进行评价。方法35只雄性Wistar大鼠随机分两组:正常对照组(CON组,n=10)和心力衰竭模型组(CHF组,n=25),CHF组采用阿霉素2.5 mg/kg尾静脉注射,每周一次,连续10 w,建立CHF大鼠模型。12 w时采用超声和血流动力学检测评价其心功能,放免法检测血浆肿瘤坏死因子-α、血管紧张素Ⅱ及醛固酮水平,氯胺T法检测羟脯氨酸及胶原含量,苦味酸天狼星红染色进行左室胶原特异染色及定量分析,计算胶原容积分数(CVF),并进行HE染色,观察其组织学变化。结果CHF组大鼠死亡率为40%(10/25),CON组无死亡。与CON组相比,CHF组大鼠左室舒张末期内径(LVEDD)及收缩末期内径(LVESD)增加,心功能明显下降,表现为左室短轴缩短率(FS)、二尖瓣环收缩期长轴方向峰值运动速度(Vs)、左室内压最大上升速率( dp/dtmax)、左室内压最大下降速率(-dp/dtmax)明显降低,左室舒张末期压(LVEDP)升高(P<0.01);CHF组血浆肿瘤坏死因子-α、血管紧张素Ⅱ及醛固酮水平升高(P<0.01),心肌羟脯氨酸及胶原含量较CON组增加(P<0.01);苦味酸天狼星红染色显示CHF组左室胶原明显增加,胶原容积分数(CVF)明显增高(P<0.01);病理学结果证实符合心肌病样改变。结论阿霉素多次小剂量静脉注射能导致大鼠发生心脏间质纤维化及心脏舒缩功能降低,可成功建立实验性心力衰竭大鼠模型。     

一种慢性心力衰竭模型的建立

大鼠心力衰竭(心衰)模型是研究心肌肥厚、心衰时全身血流动力学及神经内分泌变化的一种非常实用的模型，有多种造模方式，根据研究的目标而定。本文作者简述一种早期心衰模型的建立方法。     

大鼠心力衰竭模型的建立与评估

目的 评估通过腹主动脉狭窄、冠状动脉结扎及腹主动脉狭窄联合冠状动脉结扎3种方法制备大鼠心力衰竭模型的差异。方法 将雄性SD大鼠60只随机分为4组:对照组、腹主动脉狭窄组、冠脉结扎组及腹主动脉狭窄联合冠状动脉结扎组;各组大鼠在术后4周进行心脏超声观察射血分数（EF）、左室短轴缩短率（FS）、左室舒张（LVEDD）和收缩末期内径（LVESD）、左室舒张末期容积（LVEDV）和收缩末期容积（LVESV );左心室插管观测大鼠心率（HR）、左室收缩末压（LVESP）、左室舒张末压（LVEDP）及左室内压最大上升/下降速率（±dp/dtmax）,测量大鼠心脏质量,计算心脏质量/体质量比。结果 对照组和腹主动脉狭窄组4周存活率100%,冠状动脉结扎组4周存活率为86.67%,腹主动脉狭窄联合冠状动脉结扎组4周存活率为13.33%。与对照组相比,腹主动脉狭窄组的EF、FS均明显降低（P<0.05或P<0.01）,LVESD、LVESV和LVEDV明显升高（P<0.05或P<0.01）,LVEDD和其他心功能指标没有明显变化;冠状动脉结扎组的EF、FS、LVSP和±dp/dtmax均明显下降,LVEDD、LVESD、LVEDV、LVESV和LVEDP明显升高（P<0.01）;除LVEDD外,其余各项指标与腹主动脉狭窄组相比有明显差异（P<0.01）;与对照组相比,腹主动脉狭窄组的心脏质量/体质量比没有明显变化,冠脉结扎组心脏质量/体质量比明显升高（P<0.01）。结论 腹主动脉狭窄法的心衰模型4周时大鼠的EF值仍处于正常范围,心衰症状不明显;冠脉结扎4周制作的心衰模型其心衰程度更为严重,能较好地模拟心衰的临床变化。     

超声心动图在评估犬慢性心力衰竭模型中的作用

目的探讨超声心动图在评估犬慢性心力衰竭模型中的作用。方法对10只比格犬进行快速右心室起搏,起搏前及起搏4周停止起搏后进行多普勒超声心动图和血流动力学检查。结果快速右心室起搏4周后,所有犬都出现气促、四肢浮肿等情况,并有不同程度的胸、腹腔积液。超声心动图示左室EF、FS较起搏前显著降低（P<0.01）,分别为（0.63±0.05）vs（0.42±0.10）和（0.33±4.50）vs（0.19±6.19）;血流动力学检测示犬左室±dp/dtm ax较起搏前均显著降低（P<0.01）,分别为[（9846±415）vs（3330±307）mmHg/s]和[（-7925±3558）vs（-2260±113）mmHg/s]。起搏前后犬左室EF和FS值与+dp/dtm ax值呈良好的正相关（P<0.01）。结论通过超声心动图和血流动力学指标的相关性分析,表明超声心动图在评价心力衰竭动物模型上是无创、便捷、重复性好的方法。     

慢性充血性心力衰竭大鼠模型的建立

目的：探讨建立慢性充血性心力衰竭大鼠模型的方法。方法：通过结扎大鼠左冠状动脉造成大面积心肌梗死。术后8周,进行血流动力学、心室质量指数检测及心肌标本留取。结果：术后大鼠出现明显的心肌梗死改变。血流动力学提示大鼠MBP下降,LVSP,±dp／dt显著下降,LVEDP明显升高。大鼠心室质量指数增加。光镜下大鼠心肌梗死区心肌纤维明显,心肌梗死边缘心肌排列紊乱、心肌细胞肥大,核增大,部分细胞可有核固缩。结论：结扎左冠状动脉可成功制造慢性心力衰竭大鼠模型,对心力衰竭的实验研究有益。     

阿霉素诱导与冠脉结扎术建立慢性心力衰竭大鼠模型的比较

目的 比较阿霉素诱导与冠状动脉结扎术所建立的大鼠慢性心力衰竭(CHF)模型在血流动力学及组织形态学方面的差异.方法 成年雄性SD大鼠,随机分为正常对照组(对照组)、阿霉素诱导组(ADR)和冠状动脉结扎组(coronary artery ligation,CAL),10 w后测定血流动力学变化,计算心脏重量指数、心肌梗死和心室扩张数值,观察心肌组织形态学改变.结果 ADR组和CAL组死亡率分别为33.3%和20%,心脏重量指数升高17.0%和33.9%(P<0.01),以CAL组较ADR组降低更为显著(P<0.05).两CHF模型组LVSP、LV±dp/dtmax均较对照组显著降低(P<0.01),LVEDP则显著升高(P<0.01),其中CAL较ADR组更为显著;梗死面积和左心室梗死部分长度达37.46%和10.65 mm,与对照组比较,ADR和CAL组的左心室周长和内径分别增加20.8%、39.4% 和24.2%、54.1%(P<0.05,P<0.01),两CHF模型比较,CAL组LVC较ADR增加15.4%(P<0.05);肉眼可见CAL组心脏明显增大,左室心尖部出现明显的梗死区域,而ADR组除了可见心脏外观略有增大外,未见异常;光镜下病理切片显示CAL组存在心肌细胞坏死和大量的纤维化增生,ADR组部分心肌细胞呈小灶状坏死和散在的纤维化增生.结论 阿霉素诱导和冠脉结扎术均是建立CHF大鼠模型的有效方法,前者操作简单、但在进行梗死面积和纤维化增生的分析存在局限性,而冠脉结扎术所建CHF模型则能够有效避免这一不足,并能很好模拟心肌梗死后心肌肥大,并逐渐演变到心力衰竭的全部病理过程,因而与CHF更接近.     

静脉注射重组人脑利钠肽对急性心肌梗死伴心力衰竭患者的急性血流动力学效应的研究

目的前瞻性对比静脉注射重组人脑利钠肽(rhBNP)与硝酸甘油(NIT)对急性心肌梗死伴心力衰竭(AMI-CDF)患者的急性血流动力学效应及安全性。方法连续住院的42例发病在12~24h的前壁AMI-CDF的患者,随机分为静脉滴注rhBNP组(给予冲击量1·5μg/kg弹丸式静脉注射,随后以0·0075μg·kg-1·min-1维持静脉滴注3h,调整剂量0·015~0·030μg·kg-1·min-1维持静脉注射21h,然后停药观察6h)和静脉滴注射NIT组(10~100μg/min静脉注射24h,然后停药观察6h),每组21例。比较两组治疗30h内的有创血流动力学参数、尿量、相应血清生化指标和治疗1周内的主要不良心脏事件(MACE)的发生情况。结果rhBNP组和NIT组间及治疗前后中心静脉压(CVP)和收缩压(SBP)无明显变化。rhBNP组治疗30min后心率较基础值显著下降[(95·3±7·4)比(118·0±8·2)次/min,P<0·05]并维持至停药后6h;NIT组治疗2h后心率才较基础值下降,差异有统计学意义[(92·8±6·8)比(109·2±7·6)次/min,P<0·05],而停药3~6h后心率又基本恢复到治疗前水平。rhBNP组治疗30min后肺小动脉契压(PCWP)较基础值下降48·9%[(13·6±6·4)比(26·9±7·5)mmHg(1mmHg=0·133kPa),P<0·05],治疗1h后心脏指数(CI)较基础值升高27·1%[(2·8±0·4)比(2·2±0·3)L·min-1·m-2,P<0·05];治疗后2h、3h、6h、12h、18h和24h的PCWP、CI仍均较治疗前有显著改善并可保持至停药后6h(P均<0·05)。NIT组治疗后2h的PCWP亦较治疗前有显著改善[(18·1±6·8)比(25·4±7·5)mmHg,P<0·05],但CI在治疗后3h才较治疗前显著改善,且停药6h后,以上两参数即恢复至治疗前水平。两组比较,rhBNP组治疗后30min至2h的PCWP的降低和CI的增加均较NIT组更为显著(P均<0·05);此后至治疗24h,两组以上参数渐趋一致;停药6h后rhBNP组的PCWP和CI仍显著优于NIT组(P均<0·05)。rhBNP组治疗30h内总尿量较NIT组有增多趋势,且rhBNP组血清钾浓度治疗后较治疗前明显升高[(3·4±0·5)比(4·0±0·4)mmol/L,P<0·05]。本研究未发现与rhBNP相关的症状性低血压及其他严重不良反应。两组治疗1周内的主要心血管事件的发生情况相似。结论对AMI-CDF的患者静脉注射rhBNP较之NIT有着更好的急性血流动力学效应和临床效果,且安全可行。     

改良大鼠急性心肌梗死模型的制备方法

目的 探讨对大鼠急性心肌梗死模型方法进行改良的可靠性、稳定性及可重复性.方法 40只SD大鼠腹腔内注射苯巴比妥钠全身麻醉后,气管切开并插管,小动物呼吸机辅助呼吸.常规消毒铺巾后,切开左胸前区皮肤,经左侧第3、4肋间进入胸腔暴露心脏,明确左前降支冠状动脉后结扎造成急性心肌梗死.对围术期各种可导致结扎失败和死亡的原因进行分析.结果 成功建立了大鼠急性心肌梗死模型.术后24h大鼠存活率为95％,4w时存活率为92.5％.结论 通过方法改进能够快速有效建立大鼠急性心肌梗死模型并降低大鼠死亡率.     

血清脑钠肽水平对评估压力负荷性大鼠心力衰竭发展过程的价值

目的探讨血清脑钠肽(BNP)水平对评估压力负荷性大鼠心力衰竭程度分级的价值。方法雄性Wistar大鼠80只被随机分配到4周假手术组(F4)、12周假手术组(F12)、4周手术组(T4)以及12周手术组(T12)。使用腹主动脉缩窄法建立大鼠心力衰竭模型。利用电动跑台检测大鼠的运动耐量。通过右侧颈总动脉插管记录血流动力学指标:动脉收缩压(SBP)、舒张压(DBP)、平均动脉压(MBP),左室内压上升下降最大速率(±dp/dtmax)和左室舒张末压(LVDEP)。使用酶联免疫吸附法(ELISA)测定血清中BNP浓度。处死大鼠后称量心、肝、肺、肾各脏器质量,计算质量指数(脏器质量/体质量)。结果(1)各脏器质量指数:手术组全心质量指数较假手术组增大[T4组(4.3±1.6)比F4组(3.1±0.5)g/kg,P<0.05;T12组(4.0±0.3)比F12组(2.7±0.1)g/kg,P<0.01]。肺脏、肝脏、右肾质量指数在4周没有差异,到12周明显增加。(2)血流动力学分析显示:SBP、DBP及MBP在T4组开始明显升高,T12组有所降低。LVEDP和±dp/dtmaxT4组与F4组比较,差异无统计学意义,T12组LVEDP比F12组明显升高[(24.2±24.3)比F12组(3.9±5.5)mmHg,P<0.01];±dp/dtmax在T12组明显降低(P<0.01)。(3)运动耐量分析显示:T4与F4组、T12与F12组相比,大鼠耐受负荷差异均无统计学意义。(4)血清BNP水平:从术后4周即开始明显升高[T4组(298.0±88.0)比F4组(168.0±23.6)pg/mL,P<0.05],到术后12周差异有非常显著意义[T12组(475.5±121.1)比F12组(171.1±49.1)pg/mL,P<0.01]。结论与运动耐量、血流动力学指标相比,血清BNP水平的升高出现的更早,评价动物模型的心脏功能更加敏感与客观。     

小型猪慢性心肌缺血心衰模型的建立与评价

目的:建立慢性心肌缺血致心力衰竭的动物模型。方法: 小型猪18只,随机分为假手术组（n=4）和模型组（n=14）,模型组开胸于前降支近端放置ameroid缩窄环,假手术组分离前降支不套环。术后4周,行单光子发射计算机断层成像(SPECT)观察心脏灌注情况。应用无创超声心动图、有创血流动力学检查并评价心脏的舒缩功能。应用放射免疫测定法检测血清脑钠尿肽(BNP)、心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、内皮素1(ET-1)和血管紧张素Ⅱ(AngⅡ)等浓度的变化。结果: 模型组死亡2只,其余16只动物手术顺利完成。SPECT显示,模型组前降支供血区域心肌存在严重灌注障碍;假手术组无明显灌注缺损。超声心动图和血流动力学检查提示,模型组心脏的收缩和舒张功能严重受损,并发生心腔扩张,同时血清BNP的水平增高,心肌损伤标记物、炎性因子和神经体液因子的浓度也明显增高;假手术组上述参数均无显著改变。结论: 在猪的前降支近端放置ameroid缩窄环是制作慢性心肌缺血心力衰竭动物模型的有效方法。     

Neurohumoral and hemodynamic effects of ibopamine in a rat model of chronic myocardial infarction and heart failure

Summary There is increasing evidence that both neurohumoral and hemodynamic factors play a role in disease progression in chronic heart failure (CHF). To examine the influence of the oral dopamine agonist ibopamine on these factors, we studied 20 rats with chronic myocardial infarction and CHF, and compared them with 20 normal rats. After 6 weeks, rats were randomly divided between control treatment (50%) or ibopamine (50%) for 3 weeks. At the end of the study, plasma and tissue neurohumoral parameters, as well as hemodynamics, were determined. In infarcted rats, the elevated plasma norepinephrine (PNE) levels were reduced by ibopamine (251±19 vs. 138±32 pg/ml; p<0.05). Other plasma neurohormones measured (epinephrine, renin, aldosterone, and angiotensin converting enzyme [ACE]) were not significantly increased in rats with myocardial infarction and were not affected by ibopamine. Cardiac (tissue) ACE was increased in infarcted rats (12.1±1.9 U/l/min) and was significantly lowered by ibopamine (9.6±1.0 U/l/min; p<0.05); renal ACE was unaffected. Blood pressure and heart rate were similar in the two groups and were not influenced by ibopamine treatment. In conclusion, in chronic myocardial infarction and CHF in rats, ibopamine reduces the elevated levels of PNE and cardiac ACE. Further research will be needed to determine whether this effect may lead to a favorable influence on disease progression in CHF.     

Temporal trends in the frequency and longer-term outcome of heart failure complicating myocardial infarction

AIMS: To investigate trends in incidence and long-term outcome of heart failure (HF) developing within 28 days of first-ever acute myocardial infarction (AMI). METHODS AND RESULTS: We identified all residents of Perth, Western Australia aged 25-64 years, with no history of HF, who experienced a non-fatal, first-ever AMI between 1984 and 1993, and followed them for ten years. All patients (N=4006) met the criteria for 'definite AMI' in WHO MONItoring trends and determinants of CArdiovascular disease (MONICA) Project and 897 (22.4%) had early-onset HF complicating the index event. After adjustment for age, current smoking, history of diabetes and hypertension, Q-wave and anterior wall AMI, the odds of developing HF declined by 9% (odds ratio for period 1989-1993 relative to 1984-1988=0.91, 95% confidence interval (95%CI): 0.78 to 1.06). Over 10 years of follow-up, patients with early-onset HF had a cumulative average number of re-admissions of 28 per 100 as compared with 9 per 100 in patients without HF. After adjustment for age, history of diabetes and hypertension, the hazard of death in patients with early-onset HF declined by 26% (HR for the period 1989-1993 relative to 1984-1988=0.74, 95%CI: 0.57 to 0.96). CONCLUSION: Our data suggest a decline in the incidence of, and show encouraging evidence of improvement in survival after, early-onset HF complicating AMI.     

沙库巴曲缬沙坦在心肌梗死后心力衰竭中的应用进展

心力衰竭(HF)是急性心肌梗死后的严重并发症,尽管目前治疗手段众多,但病死率仍居高不下。近年来,沙库巴曲缬沙坦的出现为心血管疾病领域的治疗带来突破性进展,作为一种新型血管紧张素受体-脑啡肽酶抑制剂,已被列为治疗慢性HF的一线药物,随着在心肌梗死、高血压、糖尿病和肾脏疾病等方面的研究广泛展开,其更多的临床益处被发现。本文主要探讨沙库巴曲缬沙坦在治疗急性心肌梗死后HF中的应用进展。     

Approaches to statistical analysis of repeated echocardiographic measurements after myocardial infarction and its relation to heart failure: Application of a random-effects model

BACKGROUND: Extensive left ventricular (LV) dilatation after myocardial infarction (MI) is associated with increased heart failure risk. AIMS: To investigate whether the power to demonstrate the relation between LV dilatation and heart failure depends on the method applied to predict LV dilatation after MI. METHODS: A random-effects model and ANOVA model for repeated measurements (MANOVA) were applied to predict LV volume index during 1 year for 298 post-MI patients. Spearman correlation coefficients (r) were calculated and Cox regression analysis was used to calculate risk ratio's (RR). RESULTS: LV volume indices were more accurately predicted by a random-effects model than by a MANOVA model (systolic/diastolic respectively r = 0.93/0.91 vs. r = 0.67/0.64). Furthermore, patients with high LV volume index as predicted by the random-effects model, had significantly increased heart failure risk (systolic RR 2.04 (95% CI: 1.31 to 3.17; P = 0.001), diastolic RR 1.80 (95% CI: 1.16 to 2.78; P = 0.007). Using the same data, MANOVA failed to demonstrate this relation significantly (systolic RR 1.77 (95% CI: 0.79 to 3.98; P = 0.16), diastolic RR 1.49 (95% CI: 0.68 to 3.30; P = 0.31). CONCLUSION: When analyzing repeated measurement data, random-effect models are more powerful in detecting clinical relations than are MANOVA models, especially in the presence of missing values.     

舒张性心力衰竭动物模型建立的方法学研究

目的 :建立舒张性心力衰竭动物模型。方法 :应用心导管和超声心动图同步检查技术控制实验条件 ,通过缝扎冠状动脉造成心肌缺血使左室松弛、充盈功能减低、左室舒末压升高 ,而保持 L VEF≥ 4 5 %的实验状态。结果 :缺血即刻左室舒张末压从静息对照状态的 5 .3± 2 .8m m Hg（ 1mm Hg=0 .13 3 k Pa）升高到 7.1± 2 .8m m Hg（ P<0 .0 5 ） ,平均升高了 3 2 .4 %± 2 .8% ,左室松驰时间常数延长 ,左室舒张早期充盈速度减慢 ,L VEF从 5 7%± 6%减少到5 0 %± 8% （ P<0 .0 5 ）。结论 :通过控制实验条件可建立舒张性心力衰竭的动物模型     

急性ST段抬高型心肌梗死患者血浆微小核糖核酸-208a水平对并发急性心力衰竭的预测价值

目的:探讨血清微小核糖核酸-208a(miR-208a)表达水平对急性ST段抬高型心肌梗死(STEMI)患者并发急性心力衰竭的预测关系。方法:连续性收集2018年1月至2019年6月,就诊于我科的152例急性STEMI患者纳入病例组,并随机选择同期在我院行健康体检的志愿者60例为对照组。根据发病48 h内是否发生急性心力衰竭(AHF)将病例组分为AHF亚组和非AHF亚组。采用实时荧光定量PCR(RT-qPCR)法检测血浆miR-208a的相对表达水平。结果:病例组血浆miR-208a相对表达水平显著高于对照组(Z=10.919,P=0.000)。AHF亚组血浆miR-208a相对表达水平显著高于非AHF亚组(Z=9.573,P=0.000)。Pearson相关性分析结果显示,病例组患者血浆miR-208a相对表达水平与BNP、hsCRP和cTnI均呈正相关关系(r=0.612,P=0.000;r=0.447,P=0.000;r=0.378,P=0.000)。二分类Logistic回归分析结果显示血浆miR-208a相对表达水平是急性STEMI患者并发AHF的危险因素(OR=2.118,95%CI 1.127~3.982,P=0.007)。血浆miR-208a预测AHF的AUC为0.896(0.844,0.948),cut-off值为32.00,对应的敏感性和特异性分别为88.4%和83.3%。结论:急性STEMI患者血浆miR-208a表达水平显著升高,且可能是并发AHF的危险因素。     

Heart rate versus heart rate variability in risk prediction after myocardial infarction

INTRODUCTION: The aim of this study was to evaluate and compare heart rate and heart rate variability (HRV) in risk prediction after acute myocardial infarction (MI) and to evaluate the effect of beta-blocker treatment on the prognostic performance of heart rate and HRV. METHODS AND RESULTS: Three hundred sixty-six patients underwent 24-hour Holter recording 1 to 6 days after an MI. HRV was expressed as the standard deviation of all normal-to-normal intervals. Left ventricular systolic function was evaluated using the wall motion index. Half of the patients were taking a beta-blocker at the time of Holter recording. Mean follow-up was 44 months (median 34) after MI. By the end of follow-up, 82 patients had died. Mortality at 1 and 3 years was 12.5% and 22.6%, respectively. HRV, heart rate, wall motion index, number of ventricular premature beats per hour, and ventricular tachycardia were all significantly (P < 0.05) associated with mortality in univariate analysis, independent of beta-blocker therapy. In multivariate Cox analysis, only heart rate, wall motion index, number of ventricular premature beats per hour, and age had independent prognostic value (P < 0.001). In any model, including heart rate, HRV had no predictive value. CONCLUSION: The prognostic information of HRV is contained completely in heart rate, which carries prognostic information further than that of HRV. This result was independent of beta-blocker treatment.