The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation

Autor: Guanghui Zheng, Fenglian He, Jing Xu, Juntao Hu, Weiwei Ge, Xianfei Ji, Changsheng Wang, Jennifer L. Bradley, Mary Ann Peberdy, Joseph P. Ornato, Longyuan Jiang, Stefano Toldo, Tong Wang, Wanchun Tang
Rok vydání: 2022
Předmět:
Zdroj: Cardiovascular Drugs and Therapy. 37:423-433
ISSN: 1573-7241
0920-3206
DOI: 10.1007/s10557-021-07282-z
Popis: 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 p p p p Conclusion Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.
Databáze: OpenAIRE
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