坏死性下垂
医学
上睑下垂
心室颤动
复苏
心肺复苏术
内科学
心功能曲线
自然循环恢复
心脏病学
心肌梗塞
麻醉
细胞凋亡
炎症
炎症体
程序性细胞死亡
心力衰竭
生物
生物化学
作者
Fenglian He,Guanghui Zheng,Juntao Hu,Weiwei Ge,Xianfei Ji,Jennifer Bradley,Mary Ann Peberdy,Joseph P. Ornato,Wanchun Tang
标识
DOI:10.1016/j.ejphar.2022.175037
摘要
The systemic inflammatory response following global myocardial ischemia/reperfusion (I/R) injury is a critical driver of poor outcomes. Both pyroptosis and necroptosis are involved in the systemic inflammatory response and contribute to regional myocardial I/R injury. This study aimed to explore the effect of necrosulfonamide (NSA) on post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Sprague-Dawley rats were randomly categorized to Sham, CPR and CPR-NSA groups. For rats in the latter two groups, ventricular fibrillation was induced without treatment for 6 min, with cardiopulmonary resuscitation (CPR) being sustained for 8 min. Rats were injected with NSA (10 mg/kg in DMSO) or vehicle at 5 min following return of spontaneous circulation. Myocardial function was measured by echocardiography, survival and neurological deficit score (NDS) were recorded at 24, 48, and 72 h after ROSC. Western blotting was used to assess pyroptosis- and necroptosis-related protein expression. ELISAs were used to measure levels of inflammatory cytokine. Rats in the CPR-NSA group were found to exhibit superior post-resuscitation myocardial function, and better NDS values in the group of CPR-NSA. Rats in the group of CPR-NSA exhibited median survival duration of 68 ± 8 h as compared to 34 ± 21 h in the CPR group. After treatment with NSA, NOD-like receptor 3 (NLRP3), GSDMD-N, phosphorylated-MLKL, and phosphorylated-RIP3 levels in cardiac tissue were reduced with corresponding reductions in inflammatory cytokine levels. Administration of NSA significantly improved myocardial dysfunction succeeding global myocardial I/R injury and enhanced survival outcomes through protective mechanisms potentially related to inhibition of pyroptosis and necroptosis pathways.
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