择期经皮冠状动脉介入治疗术前负荷剂量他汀治疗对经皮冠状动脉介入治疗相关炎症及心肌损害的影响

目的探讨经皮冠状动脉介入治疗(PCI)术前阿托伐他汀预治疗对PCI相关炎症及心肌损害的影响。方法 86例拟行择期PCI的冠心病病例随机分为A组(n=30)、B组(n=26)和C组(n=30)。A组与B组术前48小时开始分别口服20mg、80mg阿托伐他汀,C组术前不服用阿托伐他汀。术后A组及C组均口服阿托伐他20mg/d,B组口服阿托伐他汀40mg/d。测定术前、术后中性粒细胞计数、超敏C反应蛋白(hs-CRP)、心肌酶、肌钙蛋白T(cTnT)、肝功能、肾功能、血脂,计算围手术期急性心肌梗死(MI)的发生率。结果 PCI术后hs-CRP、中性粒细胞计数显著升高(P<0.05);与A组和C组比较,B组△hs-CRP值显著降低,术后血清肌酸激酶同工酶(CK-MB)、cTnT降低,围手术期MI的发生率降低,术后血脂达标率最高(P<0.05)。3组PCI术前术后肝功能、肾功能、肌酸激酶等指标差异无统计学差异(P>0.05)。结论 PCI术前48小时阿托伐他汀80mg治疗可以通过抑制PCI相关炎症,对心肌具有一定的保护作用,减少围手术期MI的发生率,且与A组和C组比较,在药物安全性上没有差别。     

Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden.     

Pharmacological postconditioning with the phytoestrogen genistein

Estrogens are known to activate the phosphatidyl-inosityl 3-kinase (PI3K)/Akt pathway, which is central in the cardioprotection afforded by ischemic postconditioning. Therefore, our goal was to investigate whether a phytoestrogen, genistein, could induce a pharmacological postconditioning and to investigate potential mechanisms. We used low doses of genistein in order to avoid tyrosine kinases inhibition. Thus, pentobarbital-anesthetized rabbits underwent a coronary artery occlusion followed by 4 h of reperfusion. Prior to reperfusion, they randomly received an i.v. injection of either saline (Control), 100 or 1000 microg/kg of genistein (Geni(100) and Geni(1000), respectively), and 10 or 100 microg/kg of 17beta-estradiol (17beta(10) and 17beta(100), respectively). Infarct size (IS, % area at risk) was significantly reduced in Gen(100), Gen(1000) and 17beta(100) but not in 17beta(10) (6+/-2, 16+/-5, 12+/-3 and 29+/-7%, respectively) vs. Control (35+/-4%). A significant decrease in the percentage of TUNEL-positive nuclei within infarcted area was observed in Gen(100) and 17beta(100) vs. Controls. The estrogen receptor antagonist fulvestrant (1 mg/kg i.v.) and the PI3K inhibitor wortmaninn (0.6 mg/kg) abolished the cardioprotective effect of genistein. Western blots also demonstrated an increase in Akt posphorylation in Gen(100). In the same group, in vitro mitochondrial swelling studies demonstrated a significant inhibition of calcium-induced opening of mitochondrial transition pore vs. Controls. In conclusion, genistein exerts pharmacological postconditioning with a similar potency as 17beta-estradiol through a pathway involving activation of the estrogen receptor, of PI3K/Akt and mitochondrial preservation. Therefore, genistein should not be only considered as an inhibitor of tyrosine kinase but also as a cardioprotective estrogen.     

Is There a Role for Beta-blockers in Hypertensive Diabetic Patients?

Clinical trials have not yet produced long-term primary prevention data on the effects of angiotensin converting enzyme inhibitors, calcium antagonists or alpha-blockers on cardiovascular complications and sudden death in hypertensive patients. Large-scale secondary preventive studies on calcium antagonists have been disappointing. In contrast, beta-blockers have an established role in cardioprotection both in primary and secondary preventive studies and there is evidence to show that the cardioprotective effect of beta-blockers is even greater in the diabetic population. Furthermore, this favourable impact of beta-blockers was achieved despite diabetic patients having a worse risk factor profile and poorer prognosis. In this review the use of beta-blockers in diabetic patients will be discussed and their impact on coronary artery disease described.     

中性粒细胞与心肌缺血/再灌注损伤

背景 现已明确,炎症过程是心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)最重要的致病因素之一,而中性粒细胞是炎症反应的核心介导者.针对中性粒细胞的这种致病作用,部分研究者提出了抗中性粒细胞治疗,但是治疗效果却不尽相同,甚至大相径庭.更有研究者指出,中性粒细胞在心肌I/RI中尚发挥着一定的有益作用.针对这种现状,我们在此将中性粒细胞与心肌I/RI作一综述. 目的 评价中性粒细胞在心肌I/RI致病机制中的作用,探索抗中性粒细胞治疗的方向.内容 包括中性粒细胞对心肌I/RI的致病作用,抗中性粒细胞治疗的现状及其当前存在矛盾之处. 趋向 通过全面理解中性粒细胞在心肌I/RI中的作用,为今后进行适度的抗中性粒细胞治疗提供参考,并为今后发展多靶向联合措施治疗心肌I/RI提供思路.     

芬太尼和舒芬太尼对左旋甲状腺素钠预处理大鼠心肌保护作用的影响

目的 评价芬太尼和舒芬太尼对左旋甲状腺素钠预处理大鼠心肌保护作用的影响.方法 幼鼠采用随机数字表法随机分为7组(每组8只):空白对照组(BC组)、对照组(C组)、左旋甲状腺素钠10 μg组(10 μg组)、芬太尼组(F组)、舒芬太尼组(S组)、芬太尼联合左旋甲状腺素钠组(F+L组)和舒芬太尼联合左旋甲状腺素钠组(S+L组).采用Langendorff装置建立离体心脏缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)模型,F组和F+L组灌注液中芬太尼浓度为30 μg/L,S组和S+L组灌注液中舒芬太尼浓度为3 μg/L.结果 再灌注30 min时血流动力学F组和S组明显差于BC组;10 μg组、F+L组和S+L组优于C组、F组和S组.BC组、C组、10 μg组、F组、S组、F+L组和S+L组再灌注期的冠脉流量分别是(19±2)、(16±1)、(21±2)、(17±1)、(17±1)、(21±1)、(22±1)ml/min,并且10 μg组、F+L组和S+L组的冠脉流量高于C组、F组和S组.冠脉流出液中的肌酸激酶同工酶(creatine kinase,CK-MB)活性C组、F组和S组高于10 μg组、F+L组和S+L组.心肌热休克蛋白70(heatshock proteins70,HSP70)和肌球蛋白重链(myosin heavy-chain,MHC)α mRNA表达10 μg组、F+L组和S+L组明显强于C组、F组和S组.但是所有检测指标在10 μg组、F+L组和S+L组之间差异无统计学意义. 结论芬太尼和舒芬太尼对左旋甲状腺素钠预处理的心肌保护作用均无明显影响.