Lemoine Sandrine, Blanchart Katrien, Souplis Mathieu, Lemaitre Adrien, Legallois Damien, Coulbault Laurent, Simard Christophe, Allouche Stéphane, Abraini Jacques H, Hanouz Jean-Luc, Rouet René, Sallé Laurent, Guinamard Romain, Manrique Alain
1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
J Cardiovasc Pharmacol Ther. 2017 Nov;22(6):564-573. doi: 10.1177/1074248417702891. Epub 2017 Apr 5.
Cardioprotection against ischemia-reperfusion (I/R) damages remains a major concern during prehospital management of acute myocardial infarction. Noble gases have shown beneficial effects in preconditioning studies. Because emergency proceedings in the context of myocardial infarction require postconditioning strategies, we evaluated the effects of argon in such protocols on mammalian cardiac tissue.
In rat, cardiac I/R was induced in vivo by transient coronary artery ligature and cardiac functions were evaluated by magnetic resonance imaging. Hypoxia-reoxygenation (H/R)-induced arrhythmias were evaluated in vitro using intracellular microelectrodes on both rat-isolated ventricle and a model of border zone in guinea pig ventricle. Hypoxia-reoxygenation loss of contractile force was assessed in human atrial appendages. In those models, postconditioning was induced by 5 minutes application of argon at the time of reperfusion.
In the in vivo model, I/R produced left ventricular ejection fraction decrease (24%) and wall motion score increase (36%) which was prevented when argon was applied in postconditioning. In vitro, argon postconditioning abolished H/R-induced arrhythmias such as early after depolarizations, conduction blocks, and reentries. Recovery of contractile force in human atrial appendages after H/R was enhanced in the argon group, increasing from 51% ± 2% in the nonconditioned group to 83% ± 7% in the argon-treated group ( P < .001). This effect of argon was abolished in the presence of wortmannin and PD98059 which inhibit prosurvival phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and MEK/extracellular receptor kinase 1/2 (ERK 1/2), respectively, or in the presence of the mitochondrial permeability transition pore opener atractyloside, suggesting the involvement of the reperfusion injury salvage kinase pathway.
Argon has strong cardioprotective properties when applied in conditions of postconditioning and thus appears as a potential therapeutic tool in I/R situations.
在急性心肌梗死的院前处理过程中，针对缺血再灌注（I/R）损伤的心脏保护仍然是一个主要问题。惰性气体在预处理研究中已显示出有益作用。由于心肌梗死情况下的急救程序需要后处理策略，我们评估了氩气在此类方案中对哺乳动物心脏组织的影响。
在大鼠中，通过短暂冠状动脉结扎在体内诱导心脏I/R，并通过磁共振成像评估心脏功能。使用细胞内微电极在大鼠离体心室和豚鼠心室边缘区模型上体外评估缺氧复氧（H/R）诱导的心律失常。在人的心耳中评估缺氧复氧后收缩力的丧失。在这些模型中，在再灌注时应用氩气5分钟诱导后处理。
在体内模型中，I/R导致左心室射血分数降低（24%）和壁运动评分增加（36%），而在进行后处理时应用氩气可防止这种情况。在体外，氩气后处理消除了H/R诱导的心律失常，如早期去极化、传导阻滞和折返。氩气组中H/R后人的心耳收缩力恢复增强，从非处理组的51%±2%增加到氩气处理组的83%±7%（P<.001）。在存在渥曼青霉素和PD98059的情况下，氩气的这种作用被消除，渥曼青霉素和PD98059分别抑制促存活磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）和丝裂原活化蛋白激酶/细胞外受体激酶1/2（MEK/ERK 1/2），或者在存在线粒体通透性转换孔开放剂苍术苷的情况下，这表明再灌注损伤挽救激酶途径参与其中。
在进行后处理的情况下应用氩气具有强大的心脏保护特性，因此在I/R情况下似乎是一种潜在的治疗工具。
