Purpose

To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR).

Methods

Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups.

Results

Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05).

Conclusion

Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

中文翻译：

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选择性 NLRP3 炎症小体抑制剂 MCC950 可减轻心脏骤停和复苏大鼠模型的复苏后心肌功能障碍并提高存活率

目的

研究选择性 NLRP3 炎性体抑制剂 MCC950 对心肺复苏 (CPR) 大鼠模型复苏后心肌功能和存活率的影响。

方法

将 36 只 Sprague Dawley 大鼠随机分为三组：(1) MCC950，(2) 对照，和 (3) 假手术。每组由 6 小时非存活亚组 (n = 6) 和 48 小时存活亚组 (n = 6) 组成。心室颤动 (VF) 被诱导和未处理 6 分钟。开始心肺复苏并持续 8 分钟。尝试用 4 J 除颤进行复苏。在恢复自主循环 (ROSC) 后立即通过腹膜内注射给予 MCC950 (10 mg/kg) 或载体。在非存活亚组的 ROSC 后测量心肌功能和舌下微循环。在非存活亚组的基线和 6 小时测量白细胞介素 Iβ (IL-1β) 和心肌肌钙蛋白 I (cTnI) 的血浆水平。采集心脏组织以测量 NLRP3 炎性体成分，包括 NLRP3、凋亡相关斑点样蛋白 (ASC)、Caspase-1 和 IL-1β。在存活组中记录和评估存活时间和神经功能缺损评分 (NDS)。

结果

与对照组相比，MCC950 的复苏后心肌功能和舌下微循环得到改善 ( p  < 0.05)。与对照组相比，MCC950 中的 IL-1β 和 cTnI 有所降低 ( p  < 0.01)。与对照组相比，MCC950 治疗组的 ASC、caspase-1 和 IL-1β 显着降低 ( p  < 0.05)。ROSC 后 48 小时的存活率在 MCC950 中更高 ( p  < 0.05)，NDS 得到改善 ( p  < 0.05)。

结论

在 ROSC 后施用 MCC950 可减轻复苏后心肌功能障碍并提高生存率。