在小儿猪模型中，血流动力学导向的心肺复苏可促进成功复苏后线粒体融合并保留线粒体质量。

Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model.

作者信息

Senthil Kumaran, Morgan Ryan W, Hefti Marco M, Karlsson Michael, Lautz Andrew J, Mavroudis Constantine D, Ko Tiffany, Nadkarni Vinay M, Ehinger Johannes, Berg Robert A, Sutton Robert M, McGowan Francis X, Kilbaugh Todd J

机构信息

Children's Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States.

University of Iowa, Division of Pathology, United States.

出版信息

Resusc Plus. 2021 Apr 29;6:100124. doi: 10.1016/j.resplu.2021.100124. eCollection 2021 Jun.

OBJECTIVE

Cerebral mitochondrial dysfunction is a key mediator of neurologic injury following cardiac arrest (CA) and is regulated by the balance of fusion and fission (mitochondrial dynamics). Under stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion promotes oxidative phosphorylation efficiency. This study evaluates mitochondrial dynamics and content in brain tissue 24 h after CA between two cardiopulmonary resuscitation (CPR) strategies.

INTERVENTIONS

Piglets (1 month), previously randomized to three groups: (1) Std-CPR (n = 5); (2) HD-CPR (n = 5; goal systolic blood pressure 90 mmHg, goal coronary perfusion pressure 20 mmHg); (3) Shams (n = 7). Std-CPR and HD-CPR groups underwent 7 min of asphyxia, 10 min of CPR, and standardized post-resuscitation care. Primary outcomes: (1) cerebral cortical mitochondrial protein expression for fusion (OPA1, OPA1 long to short chain ratio, MFN2) and fission (DRP1, FIS1), and (2) mitochondrial mass by citrate synthase activity. Secondary outcomes: (1) intra-arrest haemodynamics and (2) cerebral performance category (CPC) at 24 h.

RESULTS

HD-CPR subjects had higher total OPA1 expression compared to Std-CPR (1.52; IQR 1.02-1.69 vs 0.67; IQR 0.54-0.88, p = 0.001) and higher OPA1 long to short chain ratio than both Std-CPR (0.63; IQR 0.46-0.92 vs 0.26; IQR 0.26-0.31, p = 0.016) and shams. Citrate synthase activity was lower in Std-CPR than sham (11.0; IQR 10.15-12.29 vs 13.4; IQR 12.28-15.66, p = 0.047), but preserved in HD-CPR. HD-CPR subjects had improved intra-arrest haemodynamics and CPC scores at 24 h compared to Std-CPR.

CONCLUSIONS

Following asphyxia-associated CA, HD-CPR exhibits increased pro-mitochondrial fusion protein expression, preservation of mitochondrial mass, improved haemodynamics and superior neurologic scoring compared to Std-CPR.

INSTITUTIONAL PROTOCOL NUMBER

IAC 16-001023.

目的

脑线粒体功能障碍是心脏骤停（CA）后神经损伤的关键介质，受融合与分裂平衡（线粒体动力学）调节。在应激状态下，分裂可减少线粒体质量并引发凋亡信号，而融合则可提高氧化磷酸化效率。本研究评估两种心肺复苏（CPR）策略后24小时脑组织中的线粒体动力学和含量。

干预措施

将1月龄仔猪随机分为三组：（1）标准心肺复苏组（n = 5）；（2）高剂量心肺复苏组（n = 5；目标收缩压90 mmHg，目标冠状动脉灌注压20 mmHg）；（3）假手术组（n = 7）。标准心肺复苏组和高剂量心肺复苏组经历7分钟窒息、10分钟心肺复苏及标准化的复苏后护理。主要结局指标：（1）大脑皮质线粒体融合蛋白（OPA1、OPA1长链与短链比值、MFN2）和分裂蛋白（DRP1、FIS1）的表达；（2）通过柠檬酸合酶活性评估线粒体质量。次要结局指标：（1）心脏骤停期间的血流动力学；（2）24小时时的脑功能分级（CPC）。

结果

与标准心肺复苏组相比，高剂量心肺复苏组受试者的OPA1总表达更高（1.52；四分位数间距1.02 - 1.69 vs 0.67；四分位数间距0.54 - 0.88，p = 0.001），且OPA1长链与短链比值高于标准心肺复苏组（0.63；四分位数间距0.46 - 0.92 vs 0.26；四分位数间距0.26 - 0.31，p = 0.016）和假手术组。标准心肺复苏组的柠檬酸合酶活性低于假手术组（11.0；四分位数间距10.15 - 12.29 vs 13.4；四分位数间距12.28 - 15.66，p = 0.047），但高剂量心肺复苏组得以保留。与标准心肺复苏组相比，高剂量心肺复苏组受试者在心脏骤停期间的血流动力学及24小时时的CPC评分有所改善。