Simvastatin Regulates Myocardial Cytokine Expression and Improves Ventricular Remodeling in Rats after Acute Myocardial Infarction

Purpose: Studies have showed that inflammatory cytokines were involved in the process of left ventricular (LV) remodeling after acute myocardial infarction (AMI), anti-inflammation treatment ameliorated LV remodeling and improved cardiac performance. Hydroxymethylglutary coenzyme A reductase inhibition (statins) could affect the expression of inflammatory cytokines. We hypothesized that statins have beneficial effects on early LV remodeling and cardiac performance in rats with AMI by modulating the production of inflammatory cytokines.Methods: Rats with AMI were treated with placebo or simvastatin (gastric gavage) for 4 weeks. The pro-inflammatory cytokines: tumor necrosis factor (TNF)-, interleukin (IL)-1, IL-6 and the anti-inflammatory cytokine: IL-10 excreted by cardiac myocytes was examined. Echocardiography, hemodynamics and collagen type I production were measured to evaluate LV remodeling and cardiac function.Results: The mRNA expression and protein production of TNF-, IL-1, IL-6 and IL-10 in AMI group were significantly elevated compared with sham rats. Simvastatin markedly attenuated the production of TNF-, IL-1, IL-6 and increased IL-10 levels in the noninfarcted and infarcted regions, reduced collagen deposition in the noninfarcted myocardium and improved left ventricular function. However simvastatin did not alter plasma lipids.Conclusions: Simvastatin ameliorates early LV remodeling and improve cardiac function after AMI. Simultaneously, it decreased pro-inflammatory and increased anti-inflammatory cytokines, which suggests, but does not prove, a causal relationship independent of plasma lipid-lowering effects.Jinying Zhang and Xiang Cheng contribute to the work equally.This study was supported by grants from National Natural Science Foundation of China (No. 30370574).     

Resveratrol Attenuates Ventricular Arrhythmias and Improves the Long-Term Survival in Rats with Myocardial Infarction

Objective  The effects of resveratrol treatment on ventricular arrhythmia, survival, and late cardiac remodeling were evaluated in rats with myocardial infarction (MI). Methods  Three groups of rats (sham-operated, MI, and MI pre-treated with resveratrol) were treated in an in vivo MI model by ligation of left anterior descending coronary artery. The electrocardiogram signals were monitored and recorded for 24 h using an implanted telemetry transmitter. The incidence of ventricular arrhythmias during the first 24-h after MI was also evaluated. Meanwhile, invasive in vivo electrophysiology with pacing in the right ventricle was performed in each group to assess the inducibility of ventricular arrhythmias. Results  Administration of resveratrol significantly suppressed the MI-induced ventricular tachycardia and ventricular fibrillation (0.4 ± 0.2 in Resv group vs. 7.1 ± 2.2 in MI group episodes per hour per rat, P < 0.01). Data also showed that the incidence of inducible ventricular tachycardia was lower in the Resv group than the MI group (46% vs. 81%, P < 0.01). The infarct size and mortality in the Resv group at 14 weeks were reduced by 20% and 33%, respectively, compared with the MI groups. Results from patch clamp recording revealed that resveratrol inhibited L-type calcium current (I _Ca-L), and selectively enhanced ATP-sensitive K⁺ current (I _K,ATP) in a concentration-dependent manner. Conclusion  These results suggested that the emerging anti-arrhythmic character induced by resveratrol treatment in rat hearts could be mainly accounted for by inhibition of I _Ca-L and enhancement of I _K,ATP. Administration of resveratrol also improved the long-term survival by suppressing left ventricular remodeling. You-Ren Chen and Fang-Fang Yi contributed equally to this work.     

急性心肌梗死QT离散度与恶性室性心律失常关系的探讨

目的 探讨发生急性心肌梗死时QT离散度（Q-Td）与发生恶性室性心律失常的关系.方法 测量45例患者急性心肌梗死时的Q-Td,计算校正的QT离散度（Q-TdC）.分析Q-Td、Q-TdC与恶性室性心律失常之间的关系.根据有无室性心律失常分为观察组（n=28）与对照组（n=17）.根据Q-TdC水平（分别以60ms、80ms为分界）分析其与室性心律失常和恶性室性心律失常发生的关系.结果 观察组Q-Td、Q-TdC[（70.84±29.87）ms、（79.21±33.58）ms]与对照组[（46.19±17.03）ms、（51.64±17.71）ms]相比,差异均有统计学意义（均P＜0.05）.Q-TdC≥60ms者室性心律失常发生概率（92.30%）高于Q-TdC＜60ms者（21.05%）（P＜0.05）.Q-TdC≥80ms者恶性室性心律失常发生概率（100.00%）高于Q-TdC＜80ms者（10.34%）（P＜0.05）.结论 急性心肌梗死随着Q-Td或Q-TdC值的增大,发生恶性室性心律失常的概率增高.     

急性心肌梗死Tp-e时间与恶性室性，心律失常关系的研究

目的 研究急性心肌梗死患者T波峰-末时间（Tp—e时间）与恶性心律失常的关系。方法将62例急性心肌梗死患者分为恶性室性心律失常组（观察组,n=17）和非恶性室性心律失常组（对照组,n=45）。比较两组各导联和12导联平均Tp—e时间、经心率校正的Tp—e（Tp-ec）时间。结果与对照组比较,观察组各导联和12导联平均Tp—e时间及Tp—ec显著延长,差异有显著或非常显著性意义（P〈0．05或0．01）。结论Tp—e时间可以作为预测急性心肌梗死恶性室性心律失常的指标。     

Remote Ischemic Preconditioning and Endothelial Function in Patients with Acute Myocardial Infarction and Primary PCI

Background

Remote ischemic preconditioning by transient limb ischemia reduces myocardial ischemia-reperfusion injury in patients undergoing percutaneous coronary intervention. The aim of the study we report here was to assess the effect of remote ischemic preconditioning on endothelial function in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention.

Methods

Forty-eight patients with acute myocardial infarction were enrolled. All participants were randomly divided into 2 groups. In Group I (n = 23), remote ischemic preconditioning was performed before primary percutaneous coronary intervention (intermittent arm ischemia-reperfusion through 4 cycles of 5-minute inflation and 5-minute deflation of a blood-pressure cuff to 200 mm Hg). In Group II (n = 25), standard percutaneous coronary intervention without preconditioning was performed. We assessed endothelial function using the flow-mediated dilation test on baseline, then within 1-3 hours after percutaneous coronary intervention, and again on days 2 and 7 after percutaneous coronary intervention.

Results

The brachial artery flow-mediated dilation results were significantly higher on the first day after primary percutaneous coronary intervention in the preconditioning group (Group I) than in the control group (Group II) (12.1% vs 0.0%, P = .03, and 11.1% vs 6.3%, P = .016, respectively), and this difference remained on the seventh day (12.3% vs 7.4%, P = .0005, respectively).

Conclusion

We demonstrated for the first time that remote ischemic preconditioning before primary percutaneous coronary intervention significantly improves endothelial function in patients with acute myocardial infarction, and this effect remains constant for at least a week. We suppose that the improvement of endothelial function may be one of the possible explanations of the effect of remote ischemic preconditioning.     

Effect of Short-Term Low-Intensity Exercise Training on Association of Oxygen Free Radicals and Nitric Oxide Production in Patients with Acute Myocardial Infarction

Moderate-to-high intensity of exercise training within 2 to 3 months decreases oxygen free radicals (reactive oxygen species, ROS) and increases nitric oxide (NO) in outpatients with myocardial infarction. There is no data about the association of ROS and NO after short-term low-intensity exercise training within 5 days in patients hospitalized with acute myocardial infarction (AMI). A total of 32 male patients with AMI were randomized into two groups: 15 patients with short-term low-intensity exercise training within 5 days formed the training group and 17 patients without such exercise training formed the control group. All patients performed exercise treadmill test with modified Bruce protocol before and after the study. F2-isoprostane and NO concentration of the training group increased slightly after modified Bruce exercise treadmill test. Compared with the control group, NO of the training group was also slightly higher. Baseline NO and uric acid were negative predictor variables for F2-isoprostane in all patients hospitalized with AMI, and triglyceride was a positive predictor variable. After the study, physical capacity of the training group was higher; but heart rate and systolic blood pressure were lower significantly. This study showed that short-term low-intensity exercise training for patients hospitalized with AMI did not change ROS and NO productions, but it improved physical capacity and lowered heart rate and systolic blood pressure. NO was negative predictor variable for F2-isoprostane in controlling ROS changes in dynamic compensation mechanism.     

脑心通对急性心肌梗死病人运动耐量及血管内皮功能的影响

目的研究脑心通胶囊对急性心肌梗死病人的运动耐量及血管内皮功能的影响.方法将63例急性心肌梗死病人随机分为两组,对照组(30例)予西医常规治疗;治疗组(33例)在西医常规治疗的基础上加用脑心通胶囊治疗,疗程皆为30 d,分别观察两组疗效,并用心电图平板运动试验和二维超声分别测定两组病人运动耐量及肱动脉血管内皮功能.结果经30 d治疗后,治疗组总有效率(93.9%)优于对照组(83.3%,P＜0.05);两组运动耐量均较治疗前明显提高(P＜0.05),肱动脉血管内皮功能均较治疗前明显改善(P＜0.05).结论脑心通胶囊治疗急性心肌梗死不仅可以提高疗效,而且可显著提高病人的运动耐量及改善血管内皮功能.     

溶栓治疗对急性心肌梗死患者血浆ET-1、hs-CRP、TXA2、NO水平的影响

目的探讨溶栓治疗对急性心肌梗死(AMI)患者血浆内皮素(ET-1)、超敏C反应蛋白(hs-CRP)、血栓素A2(TXA2)、一氧化氮(NO)水平的影响及其临床意义。方法病例组32例,采用尿激酶溶栓治疗,分别测出溶栓前后再通组和未通组ET-1、NO、hs-CRP、TXA2水平的动态变化。正常对照组测空腹ET-1、NO、hs-CRP、TXA2水平。结果病例组ET-1、hs-CRP、TXA2水平高于正常对照组(P<0.05),NO水平低于正常对照组(P<0.05);溶栓再通组的ET-1、NO、hs-CRP、TXA2水平显著增高,且峰值显著高于溶栓未通组的峰值(P<0.05);再通组ET-1、hs-CRP、TXA2和NO峰值提前,都在溶栓后3 h,而溶栓未通组峰值均为溶栓后5h。结论 ET-1、hs-CRP、TXA2和NO相互作用,参与了AMI的循环炎症反应和再灌注损伤,可作为判断AMI病情及溶栓治疗再通的可能指标。     

大鼠慢性缺氧性肺动脉高压中肺小动脉血红素氧合酶-1与内皮型一氧化氮合酶的变化

目的观察慢性缺氧对大鼠肺小动脉血红素氧合酶(HO)-1和内皮型一氧化氮合酶表达的影响.方法观察正常(10只,正常组)和常压问断缺氧6周大鼠(10只,模型组)的血液循环内皮细胞数、肺小动脉光镜和电镜下的改变,免疫组化法测定肺组织HO-1和内皮型一氧化氮合酶表达的变化.结果模型组血液循环内皮细胞数较正常组显著增加,血液循环内皮细胞数与右心室收缩压及肺小动脉中膜厚度呈正相关.HO-1在肺小动脉内皮细胞表达显著增多,内皮型一氧化氮合酶表达明显减少.均有显著性差异(P＜0.05～0.01).结论血液循环内皮细胞数可作为间接反映缺氧性肺动脉高压血管结构重塑的参考指标.缺氧导致肺小动脉HO-1增加和内皮型一氧化氮合酶减少,对肺动脉高压的发生发展可能有一定影响.     

Comparative Investigation of the Antiarrhythmic Effect of Propafenone (Rytmonorm) and Lidocaine in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction

ABSTRACT Propafenone, a new class I antiarrhythmic drug, given as a bolus injection followed by oral medication, or lidocaine were given to 20 consecutive patients admitted with chest pain suggesting acute myocardial infarction and showing high grades, i.e. multiform, pairs or R-on-T premature ventricular complexes or short runs of ventricular tachycardia. Before institution of therapy the mean number (±1 SD) of premature ventricular contractions (PVCs) per hour was 169±123 in the lidocaine group and 324±440 in the propafenone group. During the next 24 hours lidocaine reduced the numbers of PVCs by 73% and propafenone by 75%. The mean number (±1 SD) of 5-minute periods with high grade PVCs was 4.3±2.9 in the lidocaine group and 5.8±4.5 in the propafenone group. During therapy this number was equally reduced in both groups to 2.4. One patient in the lidocaine group developed ventricular fibrillation and three patients in the propafenone group were excluded because of increasing numbers of PVCs. One patient in the propafenone group showed a torsade-de-pointes ventricular tachycardia.     

养心通脉方含药血清预处理内皮祖细胞对急性心肌梗死兔心肌bFGF、VEGF水平的影响

目的观察养心通脉方含药血清预处理内皮祖细胞(EPCs)对急性心肌梗死(AMI)兔心肌血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)水平的影响。方法从35只雄性SPF级兔中随机选取25只建立急性心肌梗死兔模型,随机分为模型组、中药EPCs心肌注射组、中药EPCs耳缘静脉注射组、EPCs心肌注射组、EPCs耳缘静脉注射组,每组5只,另设正常组和假手术组,各5只,通过移植干预后14 d取梗死心肌区及缺血心肌区组织,荧光定量聚合酶链式反应(PCR)检测bFGF、VEGF的mRNA表达,蛋白质印迹法(Western Blot)检测bFGF、VEGF蛋白表达。结果在梗死心肌区及缺血心肌区,中药EPCs心肌注射组和中药EPCs耳缘静脉注射组bFGF、VEGF的mRNA及蛋白表达明显高于假手术组、模型组、EPCs心肌注射组、EPCs耳缘静脉注射组,差异均有统计学意义(P<0.05),但中药EPCs心肌注射组bFGF、VEGF的mRNA及蛋白表达与中药EPCs耳缘静脉注射组比较差异均无统计学意义(P>0.05),EPCs心肌注射组bFGF、VEGF的mRNA及蛋白表达与EPCs耳缘静脉注射组比较差异均无统计学意义(P>0.05)。结论养心通脉方含药血清预处理EPCs,能够明显增加损伤心肌bFGF、VEGF表达,但耳缘静脉注射与心肌注射疗效相当。     

急性前壁ST段抬高型心肌梗死患者介入治疗前血清血管内皮生长因子与左心室重构的关联性

目的 分析急性前壁ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者入院血清血管内皮生长因子(vascular endothelial growth factor,VEGF)水平与急诊经皮冠状动脉内介入术(percutaneous coronary intervention,PCI)后6个月左心室重构(left ventricular remodeling,LVR)的关联性。方法 纳入2016年1月至2017年12月在新疆自治区人民医院心血管内科行急诊PCI的急性前壁STEMI患者,收集其入院时临床资料和血液样本,采用酶联免疫吸附实验检测血清VEGF水平。在住院3天内和PCI后6个月分别对患者进行心脏超声检查,根据左心室舒张末期容积(left ventricular end-diastolic volume,LVEDV)变化情况将患者分为LVR组(n=43)和非LVR组(n=156),其中LVR定义为随访6个月时LVEDV较基线水平增加≥20%。比较两组患者的临床变量,并采用logistic回归方程分析各变量与发生LVR的关联性。结果 LVR组患者高血压(39.5%)、2型糖尿病(30.2%)、多支血管病变(46.5%)、PCI后慢血流(18.6%)的比例以及症状出现至球囊通过时间[(5.63±2.66)h]显著高于非LVR组患者[23.7%、13.5%、28.2%、6.4%、(4.39±2.14)h],差异有统计学意义(P均＜0.05)。LVR组患者入院后肌钙蛋白I峰值水平[(30.72±17.06)ng/mL]显著高于非LVR组患者[(23.61±15.95)ng/mL],而入院VEGF水平[(113.23±39.44)pg/mL]低于非LVR组患者[(133.05±43.75)pg/mL],差异有统计学意义(P均＜0.05)。Logistic回归分析显示,校正年龄、高血压、症状出现至球囊通过时间、多支血管病变、术后慢血流等因素后,2型糖尿病(OR=2.518,95% CI 1.02~6.175,P=0.044)与肌钙蛋白I峰值(OR=1.032,95% CI 1.002~1.063,P=0.034)是STEMI患者PCI后6个月出现LVR的独立危险因素,而入院时血清VEGF水平(OR=0.987,95% CI 0.967~0.999,P=0.037)是其保护性因素。结论 入院血清VEGF水平与急性前壁STEMI患者PCI后6个月发生LVR密切相关,有助于对STEMI患者进行危险分层和评估预后。     

心复康口服液对心肌梗死后心衰大鼠心肌组织mit—CK mRNA及蛋白表达的影响

目的观察心复康口服液对心肌梗死心衰大鼠心肌组织线粒体肌酸激酶（mit—CK）mRNA及蛋白表达的影响。方法采用结扎SD大鼠左冠状动脉前降支复制心肌梗死后心衰大鼠模型,用心复康口服液于术后24h灌胃给药至6周;以卡托普利作为阳性对照药,观察大鼠梗死周围心肌组织mit—CK mRNA及mit—CK蛋白表达水平。结果第6周末,与模型组比较,卡托普利组、心复康口服液组心肌mit—CK mRNA、mit—CK蛋白表达均上调（P〈0．01）。第6周末,与卡托利组比较,心复康口服液组心肌mit—CK mRNA表达水平下调（P〈0．05）,心肌mit—CK蛋白表达水平差异无统计学意义（P〉0．05）。结论心复康口服液可上调心肌梗死后心衰大鼠心肌细胞mit—CK mRNA的表达,促进mit—CK蛋白含量增加,达到改善心肌细胞能量穿梭紊乱,重塑心肌梗死后心衰大鼠心肌能量代谢作用。