Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine.
Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine.
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DOI：
10.1093/ejcts/ezx467
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发表时间：
2018-07-01
期刊：
影响因子：
--
通讯作者：
Kilbaugh TJ
中科院分区：
文献类型：
--
作者：
Mavroudis CD;Karlsson M;Ko T;Hefti M;Gentile JI;Morgan RW;Plyler R;Mensah-Brown KG;Boorady TW;Melchior RW;Rosenthal TM;Shade BC;Schiavo KL;Nicolson SC;Spray TL;Sutton RM;Berg RA;Licht DJ;Gaynor JW;Kilbaugh TJ
深低温停循环（DHCA）在新生儿心脏手术中的应用仍存在争议。脑线粒体生物能量学的改变被认为有助于DHCA中的缺血再灌注损伤。本研究的目的是比较脑线粒体生物能量学DHCA与深低温持续灌注使用新生猪模型。将24头仔猪（平均体重3.8 kg）置于心肺转流（CPB）中：10头在冷却至18 ℃后接受40 min DHCA，10头接受40 min DHCA，10头保持深低温40 min;随后将动物复温至正常体温。4例患者全程维持常温CPB。在CPB时收获新鲜脑组织，并评估线粒体呼吸和活性氧的产生。在整个分析过程中收集脑微透析样品。DHCA组动物的线粒体复合物I呼吸、最大氧化磷酸化、呼吸控制率显著降低，线粒体活性氧显著增加（P均< 0.05）。DHCA动物在复温期间和复温后，脑缺血（乳酸/丙酮酸比）和神经元死亡（甘油）的脑微透析指标也显著增加。与深低温连续灌注相比，DHCA与线粒体生物能量学的破坏有关。保护线粒体健康可以减轻心脏手术患者的脑损伤。需要进一步研究以更好地了解新生儿心脏手术中神经损伤的机制，并将线粒体功能障碍与神经结局联系起来。
Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia–reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.
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影响因子：
5.4
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
通讯作者：
Berg RA
影响因子：
8.8
作者：
Han F;Da T;Riobo NA;Becker LB
通讯作者：
Becker LB
影响因子：
4.4
作者：
Kilbaugh, Todd J.;Karlsson, Michael;Margulies, Susan S.
通讯作者：
Margulies, Susan S.
影响因子：
4.6
作者：
Salazar, Jorge D.;Coleman, Ryan D.;DiGeronimo, Robert
通讯作者：
DiGeronimo, Robert
影响因子：
16.6
作者：
Ehinger JK;Piel S;Ford R;Karlsson M;Sjövall F;Frostner EÅ;Morota S;Taylor RW;Turnbull DM;Cornell C;Moss SJ;Metzsch C;Hansson MJ;Fliri H;Elmér E
通讯作者：
Elmér E