缺血后处理在先天性心脏病手术中对未成熟心肌的保护作用

近年来,缺血后处理(I-postc)作为一种传统心肌保护方式以外的有效途径,已被越来越多的应用于临床实践中。其用于成熟心肌的保护效果得到较一致的肯定。未成熟心肌结构、代谢及功能较成熟心肌差别较大,针对未成熟心肌I,-postc心肌保护效果的临床研究以及与传统心肌保护方法(包括缺血预处理)比较和协同研究报道较少。现就I-postc的心肌保护机制、研究现状及其在未成熟心肌保护中的应用进行综述。     

A critical cytoprotective role of endogenous adrenomedullin in acute myocardial infarction

Exogenous administration or transfection of adrenomedullin (AM) affords protection against ischaemia-reperfusion injury. Here we have examined the role of endogenous AM in regulating the development of myocardial infarction. Wild type (WT) and AM(+/-) mice underwent 30 min regional myocardial ischaemia and 120 min reperfusion. In AM(+/-) hearts, tetrazolium-determined infarct size was greater than in WT controls (27.9 +/- 2.0 vs. 17.7 +/- 2.4%, P < 0.01) and mortality rate was increased (35% vs. 14%, P < 0.05). Treatment with exogenous recombinant AM (200 ng/kg) prior to coronary occlusion rescued the ischaemia-reperfusion intolerant phenotype of AM(+/-) mice and further limited infarct development in WT mice. Administration of recombinant AM was associated with augmented phosphorylation of Akt and eNOS in early reperfusion suggesting a role for AM in regulating this survival pathway. These studies provide the first evidence that expression of AM is a critical factor regulating myocardial tolerance to ischaemia-reperfusion injury.     

Normothermic blood polarizing versus depolarizing cardioplegia in a porcine model of cardiopulmonary bypass

Open in a separate window OBJECTIVESWe have previously demonstrated beneficial cardiac protection with hypothermic polarizing cardioplegia compared to a hyperkalemic depolarizing cardioplegia. In this study, a porcine model of cardiopulmonary bypass was used to compare the protective effects of normothermic blood-based polarizing and depolarizing cardioplegia during cardiac arrest.METHODSThirteen pigs were randomized to receive either normothermic polarizing (n = 8) or depolarizing (n = 5) blood-based cardioplegia. After initiation of cardiopulmonary bypass, normothermic arrest (34°C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Primary outcome was myocardial injury measured as arterial myocardial creatine kinase concentration. Secondary outcome was haemodynamic function and the energy state of the hearts.RESULTSDuring reperfusion, release of myocardial creatine kinase was comparable between groups (P = 0.36). In addition, most haemodynamic parameters showed comparable results between groups, but stroke volume (P = 0.03) was significantly lower in the polarizing group. Adenosine triphosphate levels were significantly (18.41 ± 3.86 vs 22.97 ± 2.73 nmol/mg; P = 0.03) lower in polarizing hearts, and the requirement for noradrenaline administration (P = 0.002) and temporary pacing (6 vs 0; P = 0.02) during reperfusion were significantly higher in polarizing hearts.CONCLUSIONSUnder normothermic conditions, polarizing blood cardioplegia was associated with similar myocardial injury to depolarizing blood cardioplegia. Reduced haemodynamic and metabolic outcome and a higher need for temporary pacing with polarized arrest may be associated with the blood-based dilution of this solution.     

异氟醚预处理延迟相对兔心肌缺血再灌注损伤的保护作用

目的探讨不同浓度异氟醚预处理延迟相对兔心肌缺血再灌注损伤的影响。方法30只健康新西兰雄性大白兔随机分成三组:1组:缺血再灌注组,行冠状动脉左前降支阻断40 min,再灌注120 min;2组:1.0%异氟醚预处理组,予以1.0%异氟醚 100%氧气持续吸入2 h后停止吸入异氟醚,于24 h后同1组处理;3组:2.0%异氟醚预处理组,予以2.0%异氟醚 100%氧气持续吸入2 h后停止吸入异氟醚,于24 h后同2组处理。各组分别于左冠前降支阻断前20 min(T1)、左冠前降支阻断20 min(T2)、左冠前降支阻断40 min(T3)、心肌再灌注1 h(T4)心肌再灌注2 h(T5)五个时点取颈内动脉血测定肌钙蛋白(cTnI)浓度。再灌注结束后观察心肌超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及心肌细胞超微结构的变化。用伊文思蓝和TTC染色法测心梗面积,同时观察心肌细胞超微结构变化。结果①2组和3组肌钙蛋白增高程度低于1组(P<0.05)。②心肌梗死面积:2组(24.2%±2.1%)和3组(19.7%±2.8%)低于1组(37.8%±1.7%)(P<0.05)。③心肌细胞电镜观察显示预处理组心肌细胞损伤轻于对照组。④2组和3组MDA较1组降低(P<0.05),SOD较1组增高(P<0.05)。结论异氟醚预处理延迟相对兔心肌缺血再灌注损伤有保护作用。     

硝酸异山梨酯后处理对大鼠在体心肌缺血/再灌注损伤保护作用的研究

目的观察硝酸异山梨酯后处理对大鼠在体心肌缺血/再灌注损伤是否具有保护作用，并探讨其作用机制，为实现硝酸酯后处理心肌保护新模式的临床应用与推广提供理论依据。 方法清洁级雄性Wistar大鼠，32只，10-12周龄。建立大鼠在体心肌缺血-再灌注模型；随机分为以下四组：假手术组（sham组）；缺血/再灌注组（the ischemia/reperfusion group, I/R组）；缺血后处理组（ischemic postconditioning group ,IPostC组）；硝酸异山梨酯（异舒吉 UCB Pharma GmbH.德国）后处理组（ isosorbide dinitrate postconditioning group, PPostC组）。实验结束后，测定各组大鼠心肌梗死面积，并用Elisa法测定大鼠血清肌钙蛋白I(cTnI)、丙二醛（MDA）、超氧化物歧化酶（SOD）水平。 结果（1）各组大鼠左室质量和缺血面积无统计学差异，IPostC组及PPostC组与I/R组相比，心肌梗死面积减小有统计学意义（P<0.05），分别为（41.015±1.037）%、（38.129±0.726）、（52.190±1.216）%；而IPostC组与PPostC组之间无统计学差异（P=0.057）。（2）与sham组相比，I/R组、 IPostC组和PPostC组血清cTnI的水平显著升高（p<0.05）；与I/R组相比，IPostC组和PPostC组的大鼠血清cTnI水平明显降低（p<0.05），IPostC组和PPostC组相比无统计学差异（p>0.05）。（3）与sham组相比，I/R组、IPostC组及PPostC组血清MDA水平显著升高，SOD水平显著降低（p<0.05）；与I/R组相比，IPostC及PPostC能有效降低血清MDA水并显著升高血清SOD水平(P均<0.05)。 结论（1）缺血后处理能够减轻再灌注损伤；（2）硝酸异山梨酯后处理可以产生与缺血后处理相似的心肌保护效果；（3）硝酸异山梨酯的心肌保护作用机制可能与减少活性氧的产生以及提高心肌的抗氧化（应激）能力有关。