Harisseh Rania, Chiari Pascal, Villedieu Camille, Sueur Pauline, Abrial Maryline, Fellahi Jean-Luc, Ovize Michel, Gharib Abdallah
*INSERM UMR 1060, CarMeN Laboratory, Univ Lyon1, IHU OPERA, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France; †Service d'Anesthésie Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France; and ‡Service d'Explorations Fonctionnelles Cardiovasculaires & CIC de Lyon, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France.
J Cardiovasc Pharmacol. 2017 May;69(5):326-334. doi: 10.1097/FJC.0000000000000479.
Volatile anesthetics are known to limit myocardial ischemia-reperfusion injuries. Mitochondria were shown to be major contributors to cardioprotection. Cyclophilin D (CypD) is one of the main regulators of mitochondria-induced cell death. We compared the effect of isoflurane, sevoflurane, and desflurane in the presence or absence of CypD, to clarify its role in the mechanism of cardioprotection induced by these anesthetics.
Oxidative phosphorylation, mitochondrial membrane potential, and H2O2 production were measured in isolated mitochondria from wild-type (WT) or CypD knockout mice in basal conditions and after hypoxia-reoxygenation in the presence or absence of volatile anesthetics.
All volatile anesthetics inhibited mitochondrial state 3 of complex I, decreased membrane potential, and increased adenosine diphosphate consumption duration in both WT and CypD knockout mice. However, they differently modified H2O2 production after stimulation by succinate: CypD ablation reduced H2O2 production, isoflurane decreased H2O2 level in WT but not in CypD knockout mice, sevoflurane affected both lines whereas desflurane increased H2O2 production in CypD knockout and had no effect on WT mice.
This study showed different effects of isoflurane, sevoflurane, and desflurane on mitochondrial functions and highlighted the implication of CypD in the regulation of adenosine diphosphate consumption and complex I-induced radical oxygen species production.
已知挥发性麻醉剂可限制心肌缺血-再灌注损伤。线粒体被证明是心脏保护的主要贡献者。亲环蛋白D（CypD）是线粒体诱导细胞死亡的主要调节因子之一。我们比较了在存在或不存在CypD的情况下异氟烷、七氟烷和地氟烷的作用，以阐明其在这些麻醉剂诱导的心脏保护机制中的作用。
在基础条件下以及在存在或不存在挥发性麻醉剂的情况下进行缺氧-复氧后，测量野生型（WT）或CypD基因敲除小鼠分离线粒体中的氧化磷酸化、线粒体膜电位和过氧化氢生成。
所有挥发性麻醉剂均抑制WT和CypD基因敲除小鼠中复合物I的线粒体状态3，降低膜电位，并延长二磷酸腺苷消耗持续时间。然而，它们在琥珀酸刺激后对过氧化氢生成的影响不同：CypD基因敲除减少了过氧化氢生成，异氟烷降低了WT小鼠而非CypD基因敲除小鼠中的过氧化氢水平，七氟烷对两者均有影响，而地氟烷增加了CypD基因敲除小鼠中的过氧化氢生成，对WT小鼠无影响。
本研究显示了异氟烷、七氟烷和地氟烷对线粒体功能的不同影响，并强调了CypD在调节二磷酸腺苷消耗和复合物I诱导的活性氧生成中的作用。
