Sevoflurane Suppresses Cardiomyocyte Pyroptosis in Myocardial Ischemia via NLRP3 Inflammasome Signaling.

The purpose of this study was to investigate the impact of sevoflurane (SEV) on cardiomyocyte (CM) pyroptosis following myocardial ischemia (MI). Reverse validation was performed by pharmacologically activating NLRP3 with monosodium urate (MSU) to confirm that SEV's cardioprotective effects were specifically mediated through the NLRP3 inflammasome pathway. Sprague Dawley rats were randomly assigned to sham (sham), model (conventional anesthesia + MI-reperfusion [MIR] injury modeling), SEV (SEV inhalation anesthesia + MIR injury modeling), and SEV + NLRP3 (SEV inhalation anesthesia + MIR injury modeling + NLRP3) groups. The myocardial area at risk (MAAR) and the myocardial infarct size (MIS) were evaluated in each experimental group, and cardiac tissue was examined using hematoxylin-eosin (H&E), Masson trichrome, and TUNEL staining. The concentrations of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), oxidative stress (OS), and pyroptosis-associated proteins and various inflammatory markers in the serum and cardiac tissue were quantified. Results showed that compared to the sham group, both model and SEV groups exhibited a significant increase in MAAR and MIS, accompanied by severe histopathological damage and noticeable OS (p  < 0.05). Elevated levels of inflammatory factors, enhanced CM apoptosis, and increased expression of pyroptosis-associated proteins were also observed in these groups. Notably, the SEV intervention in the SEV group demonstrated evident mitigation of heart injury, reduced MAAR and MIS, diminished CM apoptosis and inflammatory factors, and suppressed pyroptosis-associated proteins. Additionally, we observed that NLRP3 activation significantly diminished the protective effects of SEV on MIR rats. This study uncovers a novel mechanism through which SEV suppresses CM pyroptosis by inhibiting NLRP3, as confirmed by pharmacological activation of NLRP3. This was evidenced by worsened histopathological damage, increased CM apoptosis, and higher levels of inflammatory factors, cardiac injury markers, and pyroptosis-associated proteins. Overall, SEV inhibits CM pyroptosis and mitigates OS and inflammation through the NLRP3 inflammasome.