Inhaled carbon monoxide provides cerebral cytoprotection in pigs.

Inhaled carbon monoxide provides cerebral cytoprotection in pigs.
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DOI:
10.1371/journal.pone.0041982
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Pigula FA
Pigula FA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mahan VL;Zurakowski D;Otterbein LE;Pigula FA

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低浓度的一氧化碳 (CO) 对许多临床前小动物脑损伤模型具有保护作用。然而,尚未测试大型动物脑损伤模型的保护作用。心脏直视手术后的神经功能缺损可能部分与体外循环手术期间发生的缺血再灌注损伤有关。我们利用仔猪深低温停循环 (DHCA) 模型,评估了 CO 减少脑损伤的作用。 DHCA 和心肺旁路 (CPB) 引起代谢需求的显着改变,包括氧/葡萄糖指数 (OGI) 降低、乳酸/葡萄糖指数 (LGI) 增加和脑血压升高,最终导致新皮质和海马细胞死亡增加,而在用低、安全剂量的 CO 预处理的仔猪中,这种情况完全消除。此外,经过 CO 处理的动物在 CPB 前保持正常的 OGI 和 LGI 以及相应的脑窦全身血流动力学或代谢中间体没有变化的压力。总的来说,我们的数据表明,吸入 CO 可能有益于预防 DHCA 引起的脑损伤,并为接受 DHCA 心脏直视手术的新生儿提供重要的治疗选择。
Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery.
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