医学
异丙酚
神经保护
伊诺斯
脑灌注压
麻醉
蛋白激酶B
药理学
灌注
自然循环恢复
细胞凋亡
一氧化氮
内科学
一氧化氮合酶
心肺复苏术
复苏
生物
生物化学
作者
Wei‐Tien Chang,Min-Hsuan Hsu,Woan-Yi Wang,Chunpei Lee,Chih-Hung Wang,Min‐Shan Tsai,Ming‐Ju Hsieh,Hsiao-Ju Cheng,Chien-Hua Huang,Wen-Jone Chen
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2018-11-06
卷期号:138 (Suppl_2)
标识
DOI:10.1161/circ.138.suppl_2.103
摘要
Introduction: Neurological outcome after cardiac arrest (CA) and CPR is usually unsatisfactory even in this era of target temperature management (TTM). Propofol is not only a useful sedative drug for TTM but confers neuroprotective effect. We previously showed that propofol combined with TTM improves survival in patients resuscitated from CA. In this study we aimed to explore the underlying mechanism focusing on cerebrovascular circulation and anti-apoptosis signaling. Hypothesis: Infusion of propofol in the early post-CA phase improves cerebral perfusion and mitigates neuronal apoptosis via Akt-eNOS signaling. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, propofol infusion (20 mg/kg/h) was instituted after return of spontaneous circulation (ROSC) and continued in the first 2 h. Hemodynamics were monitored and the cerebral perfusion was continuously recorded by OxyFLO probe. The arterial blood was regularly sampled for measurement of reactive oxygen species (ROS, chemiluminescence method) and NO (demonstrated by nitrate/nitrite). Two hours after ROSC, the brain was harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). Results: After CA and CPR, the cerebral perfusion was significantly reduced to ~0.5 folds that of baseline. With the infusion of propofol, the cerebral perfusion was significantly increased from the beginning after ROSC ( P < 0.01 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P < 0.01) while ROS abrogated ( P < 0.05). The cleaved caspase-3/caspase-3 of the brain was markedly reduced ( P < 0.001), suggesting anti-apoptotic neuroprotection. When exploring the mechanism, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were significantly increased (both P < 0.001), indicating activation of Akt-eNOS-NO signaling. Conclusions: Infusion of propofol in the early post-CA phase reduces oxidative stress, improves cerebral perfusion, and ameliorates neuronal apoptosis. The protection is, at least in part, mediated via activation of Akt-eNOS-NO signaling.
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