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。     

重组人红细胞生成素在妇科围手术期贫血治疗中的应用研究现状

抗对于妇科围手术期患者,由于术前贫血、术中失血或术后炎症,可能导致贫血状况愈加严重,而旨在改善患者预后和减少异体输血的妇科围手术期血液管理措施越来越被重视。重组人红细胞生成素能显著升高贫血患者血红蛋白水平并减少输血需求,其应用于围手术期贫血的纠正,已成为临床研究的新热点。综述重组人红细胞生成素治疗妇科围手术期贫血的作用机制、国内外临床研究及安全性研究。     

核因子-kappa B在肢体缺血预处理早期心肌保护中的作用

目的:探讨非创伤性肢体缺血预处理对缺血/再灌注心肌的作用及核因子kappa B(NF-kB)在诱导远隔器官预处理中的可能机制.方法:Wistar大鼠48只,制备心肌缺血/再灌注模型,随机分3组,缺血/再灌注组(I/R组),非创伤性肢体缺血预处理组(PL组),ProDTC非创伤性肢体缺血预处理组(PL-D组).观察各组心肌梗死面积,并应用反转录PCR技术,测定心肌组织NF-kB mRNA.结果:心肌梗死面积PL组较I/R组明显减少,分别为34.5%±7.6%和58.5%±8.5%(P<0.05),而PL-D组与I/R组相比无显著差异.与I/R组比较,PL组和PL-D组NF-kB mRNA表达明显减弱(P<0.05);PL-D组NF-kB mRNA表达较PL组亦明显减弱(P<0.05).结论:非创伤性肢体缺血预处理对缺血再灌注心肌有早期保护作用,NF-kB在肢体缺血预处理的早期心肌保护中起重要作用.     

冠状静脉窦逆行灌注和冠状动脉桥灌注在心脏外科手术的应用

目的总结和分析心脏外科手术中应用冠状动脉顺行灌注联合冠状静脉窦逆行灌注和冠状动脉桥灌注技术进行心肌保护。方法30例患者分为2组:A组(顺灌联合逆灌技术)20例和B组(顺逆灌结合桥灌技术)10例,疾病种类有:冠心病合并瓣膜病、冠心病合并室壁瘤、升主动脉病变合并主动脉瓣病变和单纯瓣膜病变。结果术中转流平稳,血流动力学稳定,监测指标均在正常范围,无手术死亡和围手术期并发症。结论采用冠状动脉顺行灌注联合冠状静脉窦逆行灌注或结合冠状动脉桥灌注心肌停搏液进行心肌保护,取得良好效果。     

纤维蛋白原与冠心病PCI介入治疗围术期心肌梗死的相关性

目的:探讨纤维蛋白原与冠心病介入治疗围术期心肌梗死的相关性。方法:2013年1月到2015年1月,选择在我院进行诊治的冠心病患者92例,都给予PCI介入手术治疗,在手术前后进行纤维蛋白原与心功能的测定,对围术期心肌梗死发生情况与临床资料进行调查与分析。结果:所有患者都介入手术治疗成功,术后LVESVI与LVEDVI值都明显低于术前(P0.05),而术后LVEF值明显高于术前(P0.05);术后患者的血浆纤维蛋白原值为3.66±0.42 g/L,明显低于术前的7.45±0.56 g/L(P0.05)。围手术期发生心肌梗死8例,发生率为8.7%。Spearman秩相关分析法结果显示心肌梗死发病与血浆纤维蛋白原、LVESVI、LVEDVI、LVEF值都存在明显相关性(P0.05),多元Logistic回归分析结果显示纤维蛋白原、LVESVI、LVEDVI、LVEF、年龄为导致冠心病围术期心肌梗死的主要危险因素(P0.05)。结论:介入手术治疗冠心病具有很好的效果,但是围术期心肌梗死的发生率比较高,纤维蛋白原能有效反应病变状况,在心肌梗死的发生发展中起着关键性作用。     

PCI术后心肌缺血损伤机制与治疗的研究进展

经皮冠状动脉介入治疗术(percutaneous coronary artery intervention,PCI术)是冠心病患者血运重建的重要手段,但临床观察显示PCI术后经出现慢血流、无复流,再灌注心律失常及心肌酶学的升高,直接影响患者的预后。因此,减少PCI术后的心肌损伤是改善冠心病患者经PCI术后预后的关键。目前研究认为PCI术后心肌缺血再灌注损伤的发病机制主要与心肌再灌注时与氧自由基生成增多、细胞内Ca2+超载、心肌细胞能量代谢障碍、微血管损伤、粒细胞浸润以及心肌细胞的凋亡等多方面的作用有关,而PCI术后心肌损伤的保护治疗方面主要有药物与器械两方面。本文就PCI术后心肌缺血再灌注损伤的机制及保护治疗的研究进展作一综述。     

麻醉药物在肝细胞凋亡中的作用

围术期最常用,最重要的药物是全身麻醉药(包括吸入麻醉药和静脉麻醉药),麻醉药是适应手术的需要而出现的,经过长时间的发展,它的药理作用也越来越完善。在过去几年里很多研究报道的麻醉药的药理作用与介导的细胞凋亡之间的关系主要集中在神经系统。然而,麻醉实践中大部分麻醉药物都在肝脏代谢,已有证据表明麻醉药对肝细胞也有影响。麻醉药介导的细胞凋亡作用可能与caspase通路,Bcl-2家族,TRADD,FADD等多种因素有关。但不是所有麻醉药都对肝细胞有凋亡作用,部分还具有保护作用。因此本文就现有的麻醉药对肝细胞凋亡中的作用进行了综述。     

急性心肌梗死患者冠脉搭桥术前中性粒细胞-淋巴细胞比率与 围术期心肌损伤相关分析*

摘要目的：探讨急性心肌梗死患者冠脉搭桥（CABG）术前中性粒细胞- 淋巴细胞比率（NLR）与围术期心肌损伤的关系,为临床 CABG 围术期心肌保护提供参考依据。方法：选取2012 年1 月至2012年6 月于首都医科大学附属北京安贞医院因急性心肌梗死 接受冠脉搭桥手术（CABG）患者210 例,收集术前血常规及术后肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB）,计算NLR;采用 四分位法根据NLR 水平将患者分为四组,比较各组cTnI 及CK-MB 峰值,多元逐步回归分析NLR 与cTnI 及CK-MB 峰值的相 关性。结果：随着NLR 水平升高,高血压病史和射血分数＜50%患者比例逐渐增多;白细胞计数、术后CK-MB 及cTnI峰值、术后 血肌酐值均逐渐增加;多元逐步回归分析显示,NLR、WBC分别与cTnI 峰值呈正相关（r=0.526,r=0.186,P<0.05）。结论：术前 NLR、WBC 与cTnI 峰值呈正相关,NLR 可能是反应急性心肌梗死患者冠脉搭桥围术期心肌损伤的良好标志物。     

同期行冠状动脉旁路移植和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床研究

目的:总结同期行冠状动脉旁路移植(CABG)和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床经验。方法:回顾性分析我院收治的41例接受冠状动脉旁路移植同期行心脏瓣膜置换术的冠心病合并心脏瓣膜病患者的临床资料,对手术方法、主要并发症和术后处理方法进行分析总结。结果:41例患者中,行二次开胸4例(9.76%),应用IABP 2例(4.88%),发生低心排综合征6例(14.63%)、肾功能不全6例(14.63%)、肺功能不全7例(17.07%)、脑合并症1例(2.44%)、胸腔积液4例(9.77%),死亡6例(13.63%),其余患者康复出院。结论:CABG同期行心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的近期疗效满意。术前改善心功能,成熟的手术技术,完全的心肌再血管化,良好的心肌保护,停机困难者尽早应用主动脉内球囊反搏(IABP)及加强术后处理是提高CABG同期行心脏瓣膜置换术疗效的重要措施。     

后适应缺血时间窗的选择对小鼠心肌再灌注损伤的影响

目的 探讨后适应对小鼠心肌再灌注损伤的影响以及不同缺血时间窗的后适应心脏保护作用的差异 .方法 96只成年C57/BL小鼠随机分为缺血时间30、45 min和60 min的三组,每组又分为后适应和缺血再灌注两种处理.通过开胸结扎左冠状动脉造成急性心肌梗死 ,在完全再灌注早期给予反复短暂再通/闭塞的缺血后适应.采用Evans blue和TTC染色的方法确定缺血心肌和梗死心肌面积,并测定血清的心肌酶含量、心肌超氧化物歧化酶 (SOD) 活性与丙二醛 (MDA) 水平以及血流动力学指标.结果 缺血30 min后适应组、缺血45 min后适应组心肌梗死面积分别比相同缺血时间的再灌注对照组减少53.1%和31.2%,差异均具有统计学意义(P<0.01),缺血后适应可明显降低血清心肌酶、提高心肌SOD的活性以及改善血流动力学的恶化;缺血60 min后适应组梗死心肌面积无明显降低, 差异无统计学意义(P＞0.05).结论 小鼠心肌处于轻中度水平的缺血损伤,在恢复冠脉血流的早期施行缺血后适应可以有效地减少心肌再灌注损伤,但随着缺血时间的延长,心肌保护作用就明显减弱或消失.     

Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside?

A steadily increasing number of investigations demonstrate that preconditioning with volatile anesthetics attenuates the deleterious effects of myocardial ischemia and reperfusion injury by an ischemic preconditioning-like mechanism. Thus volatile anesthetics may represent the best choice for anesthesia of patients at risk for myocardial ischemia. However, factors such as old age, coexisting conditions such as diabetes mellitus and the use of oral hypoglycemic drugs or cyclooxygenase inhibitors, timing and duration of myocardial ischemia, and possible constraints of a complicated preconditioning protocol may limit the benefits of this powerful tool under clinical conditions. The purpose of this minireview is to provide a brief overview of the results of basic and clinical research on cardioprotection by volatile anesthetics.     

药理性预适应的脑保护作用

基于对脑组织内源性保护作用缺血预适应的认识,近年来发现一些药物预处理可以诱导脑组织产生保护作用,称为药理性预适应。这些药物包括内毒素及其衍生物、3-硝基丙酸、吸入性麻醉剂、腺苷及其拟似物、ATP敏感钾通道的开放剂、吗啡类药物、去铁敏等。不同的药物诱导药理性预适应脑保护的时程和强度以及在具体机制方面存在一定差异。开发诱导脑药理性预适应的新药有望应用于神经外科及预防性脑保护。     

Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion

Ischemia is known to potently stimulate autophagy in the heart, which may contribute to cardiomyocyte survival. In vitro, transfection with small interfering RNAs targeting Atg5 or Lamp-2 (an autophagy-related gene necessary, respectively, for the initiation and digestion step of autophagy), which specifically inhibited autophagy, diminished survival among cultured cardiomyocytes subjected to anoxia and significantly reduced their ATP content, confirming an autophagy-mediated protective effect against anoxia. We next examined the dynamics of cardiomyocyte autophagy and the effects of manipulating autophagy during acute myocardial infarction in vivo. Myocardial infarction was induced by permanent ligation of the left coronary artery in green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) transgenic mice in which GFP-LC3 aggregates to be visible in the cytoplasm when autophagy is activated. Autophagy was rapidly (within 30 min after coronary ligation) activated in cardiomyocytes, and autophagic activity was particularly strong in salvaged cardiomyocytes bordering the infarcted area. Treatment with bafilomycin A1, an autophagy inhibitor, significantly increased infarct size (31% expansion) 24 h postinfarction. Interestingly, acute infarct size was significantly reduced (23% reduction) in starved mice showing prominent autophagy before infarction. Treatment with bafilomycin A1 reduced postinfarction myocardial ATP content, whereas starvation increased myocardial levels of amino acids and ATP, and the combined effects of bafilomycin A1 and starvation on acute infarct size offset one another. The present findings suggest that autophagy is an innate and potent process that protects cardiomyocytes from ischemic death during acute myocardial infarction.     

Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1

In our study, resveratrol (polyphenol) has been identified as a very important stimulus/agent for the induction of new vessel growth. Occlusion of a main coronary depletes the blood supply to the myocardium and subsequently reduces cardiac function, which ultimately leads to heart failure. Progressive, chronic coronary artery occlusion has been shown to induce development of collateral arteries to re-establish and maintain blood flow to the myocardium at risk via the growth of new capillary vessels or angiogenesis. Studies from our laboratory, as well as from others, have already confirmed the protective role of collaterals against myocardial ischemia and cell death. We have successfully demonstrated in rat myocardial infarction (MI) model an effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI. Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1. We also were able to demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI.     

External triggers of onset of myocardial infarction-an update

Coronary heart disease is one of the leading causes of death in both industrialised and developing countries. About two thirds of all coronary deaths occur outside the hospital and before any medical care can be reached. Therefore, the prevention of coronary events appears to be of utmost importance. Rupture of an atherosclerotic plaque and subsequent coronary thrombosis is the most common underlying pathophysiological mechanism of coronary events. External stresses or 'triggers' imposing on coronary plaques may precipitate plaque rupture. External triggers include physical activity, various emotional stresses, eating, environmental factors, and sexual activity. The increased relative risk of myocardial infarction may be induced by external triggers via the activation of internal triggering mechanisms such as biomechanical and hemodynamic stresses and changes in platelet aggregability and blood viscosity. Recent prospective studies have confirmed the results of earlier retrospective studies and have, similarly, shown the importance of external triggers in increasing the risk of myocardial infarction and other coronary events. Particularly, sedentary individuals with underlying coronary heart disease appear to be at risk when exposed to external triggers. Regular physical activity, on the other hand, is a protective factor against the increased risk associated with external triggers. However, health education needs to be provided about the risks associated with strenuous exercise in untrained individuals. Apart from lifestyle factors, pharmacological protection of the population at risk during vulnerable periods plays an important role as well. Medication such as beta-blockers and aspirin may lower the increased risk of coronary events during exposure to external triggers. Also, further research is needed with regard to psychosocial stressors and their potential role as external triggers of myocardial infarction and other coronary events.     

Autophagy in ischemic preconditioning and hibernating myocardium

Autophagy is a major protective mechanism and has been identified in response to hypoxia and more recently, myocardial ischemia, but it is not known whether it is involved in mediating ischemic preconditioning, the most powerful intervention known to protect myocardium against lethal ischemic injury. We examined autophagy in several models of preconditioning induced by 6 repetitive episodes of ischemia every 12 hours versus classical first or second-window preconditioning in swine. The results indicated that autophagy is an important mechanism mediating cardioprotection following repetitive episodes of coronary stenosis or coronary occlusion, but less for traditional first or second window preconditioning.     

Dynamics of endothelial progenitor cells following sevoflurane preconditioning

There is relevant evidence concerning the involvement of endothelial progenitor cells in neovascularization and wound healing. In this study we investigated the effects of sevoflurane, a volatile anesthetic with proven cardioprotective virtues, on the mobilization of bone marrow mononuclear cells with endothelial progenitor markers (CD 34+, flk-1 +), an event that may account for the protective effects of delayed anesthetic preconditioning. Male Wistar rats were treated with a mixture of air and sevoflurane (1 MAC) in cycles of 5 minutes, alternating with 5-minutes wash-out periods (the preconditioned group), or ventilated for 30 minutes with room air (control group). Following flow cytometry and immunofluorescence measurements, a considerable increase in circulating CD34+, flk-1 + and CD34+/flk-1 + cells was observed in the preconditioned group beginning at 12 hours after treatment, with a peak value at 24 hours after sevoflurane administration. These cells are a potential source of myocardial regeneration in the context of perioperative or periprocedural ischemia in patients with coronary artery disease.     

Neovascularization of ischemic myocardium by newly isolated tannins prevents cardiomyocyte apoptosis and improves cardiac function

During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases.