缺氧诱导因子-1α与脑缺氧缺血性损伤

缺氧诱导因子-1α(hypoxia-inducible factor-1 alpha,HIF-lα)是近来发现的广泛存在于哺乳动物和人体内的一种缺氧应答调控因子,在调节缺氧诱导的基因表达中起关键性作用。它可调节表达多种靶基因如血管内皮生长因子、促红细胞生成素等,对改善脑缺氧缺血后能量代谢障碍、促进脑血流动力学恢复、抑制兴奋性氨基酸毒性、减少细胞凋亡等起重要作用。通过进一步对HIF-lα及其靶基因的研究,可能为临床治疗脑缺氧缺血性损伤提供了一种新的治疗策略。     

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.     

心肌桥对冠状动脉血流储备的影响

目的　探讨心肌桥对冠状动脉血流储备的影响。方法　对 16例经冠状动脉造影诊断有心肌桥者作冠状动脉内多普勒检查 ,观察并记录壁冠状动脉及其远近段血流图形及特点 ,壁冠状动脉远段、近段的基础平均峰值流速 (bAPV)和充血平均峰值流速 (hAPV) ,分别计算出壁冠状动脉远段、近段的血流储备 (CFR)并予比较 ,作配对t检验。CFR定义为冠状动脉相同节段hAPV和bAPV的比值。结果　 16例患者的心肌桥均位于左前降支 ,其壁冠状动脉多普勒频谱血流图形呈特征性的舒张早期指尖样变化 ,壁冠状动脉近段和远段bAPV无明显差异 [(18 8± 9 2 )cm/s比 (17 5± 7 8)cm/s,P>0 0 5 ],而hAPV的增加明显高于其远段 [(5 5 5± 19 5 )cm/s比 (4 1 1± 17 9)cm/s,P <0 0 5 ]。壁冠状动脉近段CFR明显高于其远段 (3 13± 1 15比 2 38± 0 76 ,P <0 0 1)。结论　心肌桥使壁冠状动脉的多普勒血流图形呈特征性指尖样现象 ,其远段CFR下降 ,低于其近段值     

Influence of isoprostane F2alpha-III on reflow after myocardial infarction.

AIMS: To investigate whether the vasoconstrictor isoprostane F2alpha-III (iPF2alpha-III), released during myocardial reperfusion, contributes to the low/no reflow phenomenon observed following acute myocardial infarction (AMI). METHODS AND RESULTS: Thirteen patients undergoing primary percutaneous coronary intervention (PCI) for AMI had iPF2alpha-III measured by high-performance liquid and gas chromatography-mass spectrometry. Isoprostane F2alpha-III concentrations were significantly higher following PCI than in controls (1.5+/-1.3 vs.16+/-0.06 nM, p < 0.001). Mean iPF2alpha-III concentration correlated positively with ST-segment resolution at 90 min (R = 0.62, p < 0.05). In the isolated murine heart: (a) coronary vasoconstriction occurred at, or above, iPF2alpha-III concentrations of 1 microM. From 1 to 10 microM, iPF2alpha-III induced dose-dependent vasoconstriction (p = 0.005) with reduction in coronary flows (f) of 57+/-5% and 31+/-4% (percentage baseline), respectively; (b) SQ29548 1 microM completely reversed the vasoconstrictive effects of iPF2alpha-III 10 microM; (c) SQ29548 1 microM infused during reperfusion following 30 min ischaemia had no effect on CF or infarct volume. CONCLUSION: Concentrations of iPF2alpha-III released into the venous circulation during reperfusion following AMI in humans are significantly lower than those required to diminish coronary flow in the murine heart; increased levels indicate successful reperfusion. Inhibition of iPF2alpha-III has no effect on coronary flow or infarct size in the murine heart, suggesting that iPF2alpha-III alone does not account for the low/no reflow phenomenon observed following AMI.     

尿激酶不同静脉给药方式治疗急性心肌梗塞对比研究

比较尿激酶不同静脉络药方式对急性心肌梗塞（AMI）的作用。41例AMI患者随机一次静脉推注尿激酶（UK）100～150万U（甲组：20例）或半量（50～75万U）静脉推注加半量（50～75万U）静脉滴注（乙组：21例）。于治疗后90分钟行冠状动豚造影观察梗塞相关冠状动脉（IRA）前向血流情况，并记录两组住院期心脏事件、左心室功能及不良反应。两种治疗方式90分钟总IRA再通率为51．2％（21／41）。其中甲组为55％（11/2n）；乙组为4入6％（1I/21）（P＞0.05）。两组左心室功能差异天显著性。甲、乙两级死于秦衰竭分别1、2例，且住院期心脏事件发生率无明显差异。两种方法的出血和低血压不良反应均少见。尿激酶100～150万U两种静脉给药方法治疗AMI对冠状动脉再通车及住院期临床预后的影响差异不大。     

超声介导载基因微泡靶向传输血管内皮生长因子促心肌血管新生

目的　探讨超声介导载血管内皮生长因子 16 5 (VEGF165)基因靶向微泡促梗死心肌血管新生的可行性。方法　构建真核表达质粒 pcDNA3 1-/VEGFcDNA165,将其包载于脂质泡中 ,超声辐射下向鼠心肌传输。采用RT PCR、WesternBlot检测mRNA、蛋白表达 ,观察微血管密度评价血管新生效果。结果　 (1)成功构建VEGF165基因 ;(2 )脂质体微泡可包载VEGF165基因 ;(3)超声介导辐射下向心肌靶向传输VEGF165基因 ,实验组基因表达及血管密度高于空白对照组 ,但低于VEGF165基因心肌直接注射。结论　具有心肌显影功能的脂质体载VEGF165基因微泡在超声辐射下可向大鼠梗死心肌靶向传输 ,并产生促血管新生效应。     

阵发性心房颤动局灶消融后复发病例的大静脉肌袖电隔离治疗

对肺静脉内点消融治疗术后随访 2 2± 1 1 .1个月内的心房颤动 (简称房颤 )复发病例 ,在Lasso标测导管指引下 ,进行再次心内电生理检查及大静脉肌袖电隔离治疗。探讨点消融治疗阵发性房颤后复发的机制 ,并对再次经验性大静脉肌袖电隔离治疗的结果进行分析与评价。 5例患者共接受心内电生理标测和电隔离治疗 6次 (一例行第二次电隔离 ) ,除一例行右下肺静脉靶肌袖的电隔离外 ,其余病例均进行了经验性全部大静脉的电隔离 ,共电隔离心脏大静脉 1 5根 ,其中肺静脉 1 3根、上腔静脉 2根 ,即刻电隔离成功率 1 0 0 %。术后随访 1 1 .8± 8.9个月 ,均无房颤复发。因此 ,对于阵发性房颤导管射频点消融后复发病例进行经验性全部大静脉肌袖电隔离治疗可以满意控制房颤的发作。     

半胱氨酸蛋白酶抑制剂减少大鼠脑缺血模型Calpain的表达

目的研究半胱氨酸蛋白酶Caspase-3抑制剂Ac-DEVD-CMK及Calpain抑制剂ALLN干预治疗对大鼠局灶性脑缺血／再灌注模型Calpain表达的影响。方法大鼠随机分为经左侧侧脑室注射Ac-DEVD-CMK（DEVD组）、ALLN（ALLN组）、二者联合（DEVD＋ALLN组）或溶剂二甲基亚砜组（DMSO组），以及缺血对照组（MCAO组），诱导左侧MCA缺血2h，再灌注24或48h；再灌注24h进行TTC染色观察梗死灶的形成情况；分别通过原位杂交和免疫组化技术检测鼠脑中Calpain mRNA及活性蛋白的表达。结果DMSO组的各项指标与MCAO组差异无显著性；DEVD组或ALLN组缺血侧脑中Calpain mRNA及活性蛋白的表达均明显减少，二者合用作用最强。结论Caspase-3与Calpain均在缺血性脑损伤中起重要作用，针对它们进行治疗干预具有潜在的临床应用价值。     

索他洛尔对急性心肌梗死血小板活化及纤溶活性和内皮血管活性物质的影响

目的 :探讨索他洛尔对急性心肌梗死 (AMI)血小板活化、纤溶活性和内皮血管活性物质的影响。方法 :新西兰大白兔 4 0只 ,随机分为 4组 ,每组 10只 ,Ⅰ组 :假手术组 ,Ⅱ组 :AMI组 ,Ⅲ组 :利多卡因组 ,Ⅳ组 :索他洛尔组 ;Ⅱ、Ⅲ、Ⅳ组分别结扎冠状动脉左室支中点 ,4h后取血分别测定血栓素B2 (TxB2 )、6 酮 前列腺素F1α(6 keto PGF1α)、内皮素 (ET)、一氧化氮 (NO)浓度和组织型纤溶酶原激活剂 (t PA)、纤溶酶原激活剂抑制物 (PAI)活性 ;摘取心脏 ,测定心肌梗死范围。结果 :Ⅱ、Ⅲ、Ⅳ组与Ⅰ组比较 ,血浆TxB2 、ET、NO浓度和PAI活性显著升高(P <0 .0 1) ,6 keto PGF1α浓度、t PA活性显著下降 (P <0 .0 1) ,Ⅲ组与Ⅱ组比较 ,差异无显著性意义 ,Ⅳ组与Ⅱ组比较 ,血浆TxB2 、ET、NO浓度和PAI活性明显降低 (P <0 .0 1) ,6 keto PGF1α浓度、t PA活性显著升高 (P <0 .0 1) ,梗死范围减小。结论 :索他洛尔抑制AMI早期血小板活化 ,改善纤溶活性 ,减少ET和NO的释放 ,缩小心肌梗死范围