Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm

Objectives: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. Methods: Isolated Langendorff-perfused rat hearts (n=46) were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF (n=11) present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts (n=6), in which perfusion was continued without intervention; (2) postconditioned hearts (n=5) subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. Results: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. Conclusions: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart.     

七氟醚后处理对局灶性脑缺血-再灌注损伤的保护作用

目的评价在缺血后期及再灌注早期吸入不同浓度的七氟醚行后处理对大鼠局灶性脑缺血-再灌注损伤的保护作用及其剂量依赖性。方法雄性SD大鼠50只,随机分为空白对照组、吸氧组和0.5、1.0、1.5MAC七氟醚后处理组,每组10只。采用大脑中动脉线栓法阻闭(middle cerebral artery occlusion,MCAO)120min后再灌注72h制备局灶性脑缺血模型。各七氟醚后处理组于再灌注即刻的前20min和后10min给予不同浓度七氟醚吸入。再灌注后的24、48和72h行神经功能评分(NDS),并于最后一次评分后测定脑梗死容积比。结果0.5、1.0和1.5MAC组的脑梗死容积比分别为0.39±0.03,0.31±0.03和0.24±0.03(P<0.05),明显小于对照组0.53±0.05(P<0.05)。吸氧组为0.51±0.05,与对照组比差异无统计学意义。各个时间点七氟醚后处理组NDS明显优于对照组和吸氧组。结论在局灶性脑缺血-再灌注的缺血后期和再灌注早期吸入0.5、1.0和1.5MAC七氟醚行后处理均具有脑保护作用,并呈现剂量依赖性。     

七氟醚不同处理方式在法洛氏四联症根治手术中对心肌肌钙蛋白的影响及心肌保护的临床分析

目的：比较七氟醚预处理和后处理在经体外循环下（CPB）法洛氏四联症(TOF)根治手术中对患者心肌保护的效果并比较两种方法的效果差异。方法选取行法洛氏四联症根治手术患者48例,采用随机数字表法,将其分为3组,对照组Ⅰ（n=16）,2%七氟醚预处理组Ⅱ（n=16）,2%七氟醚后处理组Ⅲ（n=16）,其中对照组全程采取全凭静脉麻醉。采集手术切皮时,手术结束后6,12,24 h,测定患者血浆心肌肌钙蛋白I（cTnI）的浓度,并记录主动脉阻断时间,体外循环时间,手术时间,ICU住院时间,机械通气时间,正性肌力药物使用情况。结果3组患者一般资料、术中各指标比较差异无统计学意义(P>0.05)。各组手术切皮前血浆心肌肌钙蛋白I（cTnI）(基础值)差异无统计学意义(P>0.05)。具有可比性,与1组比较,2组,3组在手术结束后4,12,24 h血浆心肌肌钙蛋白测定值降低,差异有统计学意义（P<0.05）。术后临床观察指标具有统计学意义（P<0.05）。2组3组在各时间点测定值差异无统计学意义(P>0.05)。结论在本研究条件下,以血浆心肌肌钙蛋白I（cTnI）作为心肌保护的指标时,七氟醚缺血预处理组和七氟醚缺血后处理组均能显著降低心肌肌钙蛋白的浓度,减轻心肌缺血再灌注损伤,从而起到心肌保护作用,而两种处理方法在心肌保护方面未见明显差异。     

吡那地尔后处理大鼠缺血再灌注损伤心肌线粒体的蛋白质组学研究

 目的: 运用蛋白质组学研究方法探讨吡那地尔后处理对缺血再灌注损伤大鼠心肌的保护作用。方法: 建立Langendorff大鼠离体心脏缺血再灌注损伤模型,随机分为吡那地尔后处理组(Pina组)和缺血再灌注损伤组(I/R组),每组9只。提取心肌线粒体蛋白质行双向凝胶电泳,应用质谱鉴定差异大于2倍的蛋白质点。结果: Pina组与I/R组比较,共发现7个差异蛋白质:Pina组NADH脱氢酶1α亚复合体10亚基(NDUFA10)﹑NADH脱氢酶铁硫蛋白2(NDUFS2)和NADH脱氢酶黄素蛋白2(NDUFV2)表达低于I/R组;Pina组异柠檬酸脱氢酶α亚基(IDHA)和Δ^3,5-Δ^2,4-二烯酰辅酶A异构酶(ECH1)表达高于I/R组;另有2个蛋白质点均被鉴定为ATP合酶δ亚基,一个蛋白质点表达升高,而另一个表达降低。结论:吡那地尔后处理可能抑制了复合体Ⅰ的亚基(NDUFA10﹑NDUFS2和NDUFV2)代偿性增加,但促进了IDHA和ECH1表达并引发了ATP合酶δ亚基发生磷酸化,这些改变可能均与吡那地尔后处理保护心肌的作用有关。     

缺血预适应与后适应叠加对老年急性心肌梗死急症介入治疗后的影响

目的研究梗死前心绞痛(缺血预适应)与缺血后适应叠加对老年急性心肌梗死患者介入治疗后冠状动脉血流速度及预后的影响。方法选取12h内接受急症冠状动脉介入治疗的心肌梗死患者106例,35例有梗死前心绞痛症状并接受缺血后适应者为预适应与后适应叠加组(IPC+Postcon),37例单纯接受缺血后适应干预者为后适应组(Postcon),其余34例为单纯再灌注组(IR),测定校正TIMI帧数(CTFC)、血肌酸磷酸激酶(CK)、肌酸磷酸激酶同工酶(CK-MB)、丙二醛,术后8w测定室壁运动记分。结果IPC+Postcon组与Postcon组CTFC明显快于IR组(27.12±5.84,26.98±5.76vs.31.53±7.41,P<0.05),CK峰值与CK-MB峰值明显低于IR组(1243.35±801.31U/L,1238.67±817.26U/Lvs.1697.76±965.63U/L,P<0.05;120.97±78.28U/L,117.94±75.81U/Lvs.174.45±92.67U/L,P<0.05),IPC+Postcon组与Postcon组间无统计学差异;3组患者入院时MDA均高于对照组,术后各时点IPC+Postcon组与Postcon组均低于IR组。术后8wIPC+Postcon组与Postcon组室壁运动恢复优于IR组(1.16±0.12,1.17±0.11vs.1.31±0.15,P<0.05)。结论缺血后适应与预适应一样可以改善介入治疗后冠状动脉血流速度,减少自由基的生成,改善心功能。预适应与后适应叠加对上述功能的改善并无增强作用。     

七氟烷对不同缺血时间大脑中动脉闭塞模型的影响

目的 观察在大脑中动脉闭塞(MCAO)模型中不同缺血时间对实验结果的影响.方法 雄性SD大鼠随机分为缺血60、90和120 min 3组,在再灌注开始时吸入1.0最小肺泡浓度(MAC)七氟烷进行后处理.再灌注24h后用神经功能缺陷评分评价神经功能,氯化三苯基四氮唑(TTC)染色后计算脑梗死容积.结果 60、90和120 min缺血导致的脑梗死容积分别为26.35％、42.65％和50.02％.在90 min组,七氟烷后处理明显改善了神经功能,七氟烷组和对照组神经功能缺陷评分均数分别为1.41和2.22分,并且减小了脑梗死容积,梗死容积百分比分别为30.17％和42.65％,60和120 min组比较差异无统计学意义(P＞0.05).结论 选择恰当的缺血时间是MCAO模型动物实验取得良好实验结果的关键.     

超声斑点追踪成像技术评价腺苷药物后适应对兔心肌缺血再灌注损伤的作用

目的：采用超声斑点追踪成像(STI)技术评价腺苷药物后适应对兔心肌缺血再灌注损伤的保护作用。方法42只健康兔随机均分为3组：单纯缺血再灌注组(IR)、缺血后适应组(IPost)、腺苷药物后适应组(ATP-PPost)。制备心肌缺血再灌注模型,于冠状动脉阻断前、阻断后45 min、再灌注120 min行超声心动图检查;冠状动脉阻断后45 min每组随机抽取2只兔,其余兔实验结束后行病理学检查。结果①病理结果显示冠状动脉阻断45 min后处死的兔心肌均可见缺血梗死改变,再灌注后三组亦可见相应改变,且以 IR组为著;②冠状动脉阻断45 min后,三组模型兔左室射血分数(LVEF)减低(P <0.05),左室整体、局部 STI指标均较阻断前明显降低(P <0.01);③再灌注120 min后,IPost组整体纵向收缩期应变率(GLSrsys)、整体纵向收缩期应变(GLSsys)绝对值增高,ATP-PPost组 GLSrsys 绝对值增高,IPost 组与ATP-PPost组局部纵向收缩期应变率(SrLsys)、局部纵向舒张期应变率(SrLd)、局部纵向收缩期应变(SLsys)绝对值均明显增高(P <0.05或P <0.01);组间比较,IPost 组与 ATP-PPost 组 GLSsys、SrLsys、SLsys绝对值较 IR组增高(P <0.05)。结论 STI可准确评价缺血再灌注兔模型左室整体和局部心肌功能变化特征,准确检测出缺血后适应和腺苷药物后适应对心肌缺血再灌注损伤的保护效应。     

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping

Background

Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem.

Objectives

Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning.

Materials and methods

Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated.

Results

Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO₂ level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05).

Conclusions

Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.     

白藜芦醇干预缺血后处理对受损H9C2心肌细胞修复的研究

目的近年来研究发现白藜芦醇（Resveratrol,RSV）具有抗氧化、清除自由基、减轻缺血再灌注损伤等作用。将其与减轻缺血再灌注损伤的主要手段——缺血后处理（Ischemic Postconditioning,IPO）相结合,共同作用于体外培养的H9C2心肌细胞受损模型。方法采用免疫细胞化学、western blot以及RT-PCR等方法,观察这种共同作用对体外培养的H9C2心肌细胞受损模型细胞增殖的影响。结果 p38表达量随着RSV＋IPO的干预和时间的延长而增加;通过直观和检测cyclinA2发现H9C2细胞数量因加入干预手段有所增加,cyclinA2的表达量也有相同趋势。结论研究结果表明,该方法不仅可以抑制细胞凋亡,更具有促进细胞增殖的作用。