Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest.
Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest.
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DOI：
10.1161/jaha.115.002232
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发表时间：
2015-09-14
影响因子：
5.4
通讯作者：
Berg RA
中科院分区：
文献类型：
--
作者：
Kilbaugh TJ;Sutton RM;Karlsson M;Hansson MJ;Naim MY;Morgan RW;Bratinov G;Lampe JW;Nadkarni VM;Becker LB;Margulies SS;Berg RA
尽管心肺复苏的进展提高了心脏骤停(CA)的存活率，但神经损伤仍然存在，线粒体生物能量学受损可能是靶向神经复苏的关键。作者试图确定良好的心肺复苏和复苏后护理以及良好的传统存活率是否会导致窒息相关性室颤CA儿童模型中持续的脑线粒体生物能量学紊乱。在窒息7分钟后，随后发生室颤，5头1个月大的雌性猪(4头假猪)接受了有针对性的血压护理：将压迫深度滴定到收缩压90毫米汞柱，并给血管加压剂注射到冠脉灌注压20毫米汞柱。所有动物在自主循环恢复后4小时内接受基于方案的血管升压剂支持，然后处死。主要结果是完整的线粒体电子传递系统(ETS)功能。CA组大鼠大脑皮质(P<；0.02)和海马区(P<；0.02)的最大氧化磷酸化呼吸(OXPHOSCI+CII)显著降低，磷酸化和偶联效率显著降低(皮质，P<；0.05；海马区，P<；0.05)。复合I和复合II驱动的呼吸在CA后均显著降低(皮质：OXPHOSCI P<；0.01，ETSCII P<；0.05；海马：OXPHOSCI P<；0.03，ETSCII P<；0.01)。在海马区，最大解偶联非磷酸化呼吸(ETSCI+CII)显著降低，柠檬酸合成酶活性降低30%(P<；0.04)。CA后皮质和海马区的线粒体显示呼吸功能明显改变，尽管在窒息相关的室颤CA中进行了良好的心肺复苏和复苏后护理。对整合ETS功能的分析表明，线粒体生物能量衰竭是CA后目标定向神经复苏的目标。IACUC协议：IAC 13-001023。
Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA. After 7 minutes of asphyxia, followed by ventricular fibrillation, 5 female 1-month-old swine (4 sham) received blood pressure–targeted care: titration of compression depth to systolic blood pressure of 90 mm Hg and vasopressor administration to a coronary perfusion pressure >20 mm Hg. All animals received protocol-based vasopressor support after return of spontaneous circulation for 4 hours before they were killed. The primary outcome was integrated mitochondrial electron transport system (ETS) function. CA animals displayed significantly decreased maximal, coupled oxidative phosphorylating respiration (OXPHOSCI+CII) in cortex (P<0.02) and hippocampus (P<0.02), as well as decreased phosphorylation and coupling efficiency (cortex, P<0.05; hippocampus, P<0.05). Complex I– and complex II–driven respiration were both significantly decreased after CA (cortex: OXPHOSCI P<0.01, ETSCII P<0.05; hippocampus: OXPHOSCI P<0.03, ETSCII P<0.01). In the hippocampus, there was a significant decrease in maximal uncoupled, nonphosphorylating respiration (ETSCI+CII), as well as a 30% reduction in citrate synthase activity (P<0.04). Mitochondria in both the cortex and hippocampus displayed significant alterations in respiratory function after CA despite excellent cardiopulmonary resuscitation and postresuscitation care in asphyxia-associated ventricular fibrillation CA. Analysis of integrated ETS function identifies mitochondrial bioenergetic failure as a target for goal-directed neuroresuscitation after CA. IACUC Protocol: IAC 13-001023.