Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Emergency Medicine, Yuyao People's Hospital, Medical School of Ningbo University, Ningbo, China.
Biomed Res Int. 2020 Apr 15;2020:9136097. doi: 10.1155/2020/9136097. eCollection 2020.
Previously, the opening of mitochondrial permeability transition pore (mPTP) was confirmed to play a key role in the pathophysiology of postcardiac arrest syndrome (PCAS). Recently, we demonstrated that limb ischemic postconditioning (LIpostC) alleviated cardiac and cerebral injuries after cardiac arrest and resuscitation. In this study, we investigated whether LIpostC would alleviate the severity of PCAS through inhibiting mPTP opening.
Twenty-four male domestic pigs weighing 37 ± 2 kg were randomly divided into three groups: control, LIpostC, and LIpostC+atractyloside (Atr, the mPTP opener). Atr (10 mg/kg) was intravenously injected 30 mins prior to the induction of cardiac arrest. The animals were subjected to 10 mins of untreated ventricular fibrillation and 5 mins of cardiopulmonary resuscitation. Coincident with the beginning of cardiopulmonary resuscitation, LIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs.
After resuscitation, systemic inflammation and multiple organ injuries were observed in all resuscitated animals. However, postresuscitation systemic inflammation was significantly milder in the LIpostC group than in the control group. Myocardial, lung, and brain injuries after resuscitation were significantly improved in the LIpostC group compared to the control group. Nevertheless, pretreatment with Atr abolished all the protective effects induced by LIpostC.
LIpostC significantly alleviated the severity of PCAS, in which the protective mechanism was associated with the inhibition of mPTP opening.
先前，线粒体通透性转换孔（mPTP）的开放被证实在心搏骤停后综合征（PCAS）的病理生理学中起关键作用。最近，我们证明了肢体缺血后处理（LIpostC）可减轻心脏骤停和复苏后的心脏和脑损伤。在这项研究中，我们研究了 LIpostC 是否通过抑制 mPTP 开放来减轻 PCAS 的严重程度。
24 只雄性家猪，体重 37±2kg，随机分为三组：对照组、LIpostC 组和 LIpostC+atractyloside（mPTP 开放剂）组。在心脏骤停诱导前 30 分钟静脉注射 Atr（10mg/kg）。动物经历 10 分钟未治疗的心室颤动和 5 分钟心肺复苏。与心肺复苏开始同时，通过四个周期的 5 分钟肢体缺血和随后的 5 分钟再灌注来诱导 LIpostC。复苏后的动物监测 4 小时，并观察 68 小时。
复苏后，所有复苏动物均观察到全身炎症和多器官损伤。然而，LIpostC 组的复苏后全身炎症明显比对照组轻。与对照组相比，LIpostC 组的心肌、肺和脑损伤在复苏后得到明显改善。然而，Atr 的预处理消除了 LIpostC 诱导的所有保护作用。
LIpostC 显著减轻了 PCAS 的严重程度，其保护机制与抑制 mPTP 开放有关。
