Early Esmolol infusion can improve septic cardiomyopathy by reducing blood lactate and inhibiting cardiomyocytes pyroptosis
Objective:This study aims to evaluate the efficacy of Esmolol(ES)in septic cardiomyopathy(SCM)and explore its potential mechanisms.Methods:The study subjects were patients with SCM.After adequate resuscitation,the patients with heart rate ≥100 beats/min were randomly divided into ES group(n=34)and control group(n=34).Base-line characteristics and outcomes were analyzed.Additionally,48 male C57BL/6 mice were randomly divided into Sham,sepsis,and Esmolol treatment(sepsis+ES)groups to assess survival,echocardiographically measure left ventricular ejec-tion fraction(LVEF),and evaluate blood lactate,lactate dehydrogenase(LDH),myocardial injury markers,and inflamma-tory factor levels.HE staining was used for histopathological analysis,and Western blotting was conducted to assess protein lactylation and levels of pyroptosis-related proteins(GSDMD-N,cl-caspase 1,NLRP3).Results:Patients in the ES group experienced a reduction in ICU stay duration and blood lactate levels.ES improved survival in SCM mice,enhanced LVEF,and reduced levels of blood lactate,LDH,creatine kinase-MB isoenzyme(CK-MB),and inflammatory factors.It alleviated histopathological changes in myocardial tissue,diminished protein lactylation and expression of GSDMD-N,cl-caspase 1,and NLRP3.Exogenous lactate was found to reverse the protective effects of ES.Conclusion:ES improves SCM by lowering blood lactate levels and inhibiting myocardial cell pyroptosis,with potential involvement of protein lactylation changes.
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