Ciprofol attenuates sepsis-induced cardiomyopathy via α7 nicotinic acetylcholine receptor-dependent modulation of myocardial inflammation and NF-κB/STAT3 signaling.

Sepsis-Induced Cardiomyopathy (SIC) is a life-threatening complication with limited therapies, significantly contributing to septic mortality. This study investigated the cardioprotective effects of ciprofol, a novel anesthetic, in SIC and elucidated the role of the α7 nicotinic acetylcholine receptor (α7nAChR) pathway. Using a cecal ligation and puncture (CLP)-induced murine sepsis model, we assessed ciprofol pretreatment's impact on myocardial injury, cardiac function, survival, and inflammation. The α7nAChR antagonist methyllycaconitine (MLA) was used to investigate pathway involvement. Our findings demonstrated that ciprofol pretreatment significantly mitigated sepsis-induced myocardial injury, evidenced by reduced serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Ciprofol also improved cardiac function, indicated by increased left ventricular ejection fraction (LVEF) and fractional shortening (FS), and markedly enhanced 14-day survival. These benefits were accompanied by attenuated cardiac inflammation, characterized by reduced myocardial infiltration of CD68+ macrophages (including pro-inflammatory CD86+ M1 phenotype) and myeloperoxidase (MPO) + neutrophils, alongside decreased systemic IL-6 and TNF-α. Crucially, MLA co-administration largely abrogated ciprofol's cardioprotective and anti-inflammatory effects. Mechanistically, ciprofol modulated α7nAChR signaling, inhibiting cardiac NF-κB p65 and STAT3 phosphorylation; MLA reversed these modulatory effects. In conclusion, ciprofol exerts significant cardioprotection against SIC, primarily via an α7nAChR-dependent pathway. This pathway suppresses myocardial inflammation by reducing inflammatory cell infiltration, cytokine production, and beneficially modulating NF-κB/STAT3 signaling. These insights suggest ciprofol's potential as an anesthetic with valuable organ-protective properties for critically ill septic patients.