Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Shiraz Badurdeen, Robert Galinsky, Calum T Roberts, Kelly J Crossley, Valerie A Zahra, Alison Thiel, Yen Pham, Peter G Davis, Stuart B Hooper, Graeme R Polglase, Emily J Camm
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Abstract

Asphyxiated neonates must have oxygenation rapidly restored to limit ongoing hypoxic-ischemic injury. However, the effects of transient hyperoxia after return of spontaneous circulation (ROSC) are poorly understood. We randomly allocated acutely asphyxiated, near-term lambs to cardiopulmonary resuscitation in 100% oxygen ("standard oxygen", n = 8) or air (n = 7) until 5 minutes after ROSC, or to resuscitation in 100% oxygen immediately weaned to air upon ROSC ("rapid-wean", n = 7). From 5 minutes post-ROSC, oxygen was titrated to target preductal oxygen saturation between 90-95%. Cerebral tissue oxygenation was transiently but markedly elevated following ROSC in the standard oxygen group compared to the air and rapid-wean groups. The air group had a delayed rise in cerebral tissue oxygenation from 5 minutes after ROSC coincident with up-titration of oxygen. These alterations in oxygen kinetics corresponded with similar overshoots in cerebral perfusion (pressure and flow), indicating a physiological mechanism. Transient cerebral tissue hyperoxia in the standard oxygen and air groups resulted in significant alterations in mitochondrial respiration and dynamics, relative to the rapid-wean group. Overall, rapid-wean of oxygen following ROSC preserved striatal mitochondrial respiratory function and reduced the expression of genes involved in free radical generation and apoptosis, suggesting a potential therapeutic strategy to limit cerebral reperfusion injury.

心肺复苏后的快速氧气滴定可减轻窒息新生羔羊的脑过度灌注和纹状体线粒体功能障碍。
窒息的新生儿必须迅速恢复氧合,以限制持续的缺氧缺血性损伤。然而,人们对自发循环恢复(ROSC)后短暂高氧的影响知之甚少。我们随机将急性窒息的濒死羔羊分配到100%氧气("标准氧",n = 8)或空气(n = 7)中进行心肺复苏,直到ROSC后5分钟,或在ROSC后立即断开100%氧气复苏至空气("快速断开",n = 7)。从复苏后 5 分钟起,氧气滴定到目标导管前血氧饱和度 90-95% 之间。与空气组和快速断奶组相比,标准氧气组的脑组织氧饱和度在 ROSC 后出现短暂但明显的升高。空气组的脑组织血氧饱和度在复苏后 5 分钟开始延迟上升,与氧气的上调相吻合。氧动力学的这些变化与脑灌注(压力和流量)的类似过冲相吻合,表明这是一种生理机制。与快速断氧组相比,标准氧组和空气组的短暂脑组织高氧会导致线粒体呼吸和动力学的显著改变。总之,ROSC 后快速断氧能保护纹状体线粒体呼吸功能,并减少参与自由基生成和细胞凋亡的基因表达,这表明这是一种限制脑再灌注损伤的潜在治疗策略。
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来源期刊
Journal of Cerebral Blood Flow and Metabolism
Journal of Cerebral Blood Flow and Metabolism 医学-内分泌学与代谢
CiteScore
12.00
自引率
4.80%
发文量
300
审稿时长
3 months
期刊介绍: JCBFM is the official journal of the International Society for Cerebral Blood Flow & Metabolism, which is committed to publishing high quality, independently peer-reviewed research and review material. JCBFM stands at the interface between basic and clinical neurovascular research, and features timely and relevant research highlighting experimental, theoretical, and clinical aspects of brain circulation, metabolism and imaging. The journal is relevant to any physician or scientist with an interest in brain function, cerebrovascular disease, cerebral vascular regulation and brain metabolism, including neurologists, neurochemists, physiologists, pharmacologists, anesthesiologists, neuroradiologists, neurosurgeons, neuropathologists and neuroscientists.
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