Wang Peng, Zhang Fan, Pan Liming, Tan Yunke, Song Fengqing, Ge Qiulin, Huang Zitong, Yao Lan
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
Oxid Med Cell Longev. 2021 Mar 1;2021:6622232. doi: 10.1155/2021/6622232. eCollection 2021.
Mitochondrial fatty acid oxidation (FAO) is involved in myocardial damage after cardiopulmonary resuscitation (CPR). This study is aimed at investigating the effect of inhibiting mitochondrial FAO on myocardial injury and the underlying mechanisms of postresuscitation myocardial dysfunction. Rats were induced, subjected to 8 min of ventricular fibrillation, and underwent 6 min of CPR. Rats with return of spontaneous circulation (ROSC) were randomly divided into the Sham group, CPR group, and CPR + Trimetazidine (TMZ) group. Rats in the CPR + TMZ group were administered TMZ (10 mg/kg) at the onset of ROSC via the right external jugular vein, while rats in the CPR group were injected with equivalent volumes of vehicle. The sham rats were only administered equivalent volumes of vehicle. We found that the activities of enzymes related to cardiac mitochondrial FAO were partly improved after ROSC. TMZ, as a reversible inhibitor of 3-ketoacyl CoA thiolase, inhibited myocardial mitochondrial FAO after ROSC. In the CPR + TMZ group, the levels of mitochondrial injury in cardiac tissue were alleviated following attenuated myocardial damage and oxidative stress after ROSC. In addition, the disorder of cardiac mitochondrial metabolism was ameliorated, and specifically, the superfluous succinate related to mitochondrial reactive oxygen species (ROS) generation was decreased by inhibiting myocardial mitochondrial FAO with TMZ administration after ROSC. In conclusion, in the early period after ROSC, inhibiting cardiac mitochondrial FAO attenuated excessive cardiac ROS generation and preserved myocardial function, probably by alleviating the dysfunction of cardiac mitochondrial metabolism in a rat model of cardiac arrest.
线粒体脂肪酸氧化（FAO）参与了心肺复苏（CPR）后的心肌损伤。本研究旨在探讨抑制线粒体FAO对心肌损伤的影响以及复苏后心肌功能障碍的潜在机制。将大鼠诱导发生室颤8分钟，然后进行6分钟的心肺复苏。恢复自主循环（ROSC）的大鼠被随机分为假手术组、CPR组和CPR + 曲美他嗪（TMZ）组。CPR + TMZ组的大鼠在ROSC开始时经右颈外静脉给予TMZ（10 mg/kg），而CPR组的大鼠注射等量的溶剂。假手术组大鼠仅给予等量的溶剂。我们发现ROSC后与心脏线粒体FAO相关的酶活性部分得到改善。TMZ作为3-酮酰基辅酶A硫解酶的可逆抑制剂，在ROSC后抑制心肌线粒体FAO。在CPR + TMZ组中，ROSC后心肌损伤和氧化应激减轻，心脏组织中线粒体损伤水平得到缓解。此外，心脏线粒体代谢紊乱得到改善，具体而言，通过在ROSC后给予TMZ抑制心肌线粒体FAO，与线粒体活性氧（ROS）生成相关的多余琥珀酸减少。总之，在ROSC后的早期，抑制心脏线粒体FAO可减少心脏ROS的过度生成并保留心肌功能，这可能是通过减轻心脏骤停大鼠模型中心脏线粒体代谢功能障碍实现的。
