Esketamine alleviated cardiomyocyte ferroptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) via cyclic GMP-AMP synthase interactor.

BACKGROUND: The use of tourniquets (TQ) during the total knee arthroplasty (TKA) induced ischemia-reperfusion (I/R) injury in the limb, resulting in the release of inflammatory cytokines and reactive oxygen species (ROS), therefore leading to myocardial damage. This study aimed to investigate the effects and molecular mechanism of Esketamine on myocardial injury (MI) caused by TQ-induced I/R injury. METHODS: A randomized numerical table method was used to divide 23 patients into the C group (11 cases, ACB + conventional anesthesia) and M group (12 cases, ACB + conventional anesthesia + 0.5 mg/kg Esketamine). The levels of lactate dehydrogenase (LDH), Malondialdehyde (MDA), Fe(2+), Glutathione Peroxidase (GSH-Px), glutathione (GSH), IL-6, TNF-α, Creatine Kinase (CK) and CreatineKinase-MB (CKMB) were determined by reagent kits. The expression of CGAMP interaction factor (STING), Glutathione Peroxidase 4 (GPX4), and Ferritin Heavy Chain 1 (FTH1) was examined by Western blot. The ROS level was tested by flow cytometry. The expression of STING was validated by immunofluorescence. RESULTS: Compared with the C group, the levels of GSH-Px and GSH were increased while the levels of IL-6, TNF-α, MDA, Fe(2+), CK, CKMB, and LDH were decreased in the M group. Furthermore, esketamine relieved the OGD/R-induced increase of MDA, Fe(2+), and ROS and the decrease of GSH-Px, GSH, GPX4, and FTH1, which were reversed by STING overexpression. CONCLUSION: Esketamine alleviated cardiomyocyte ferroptosis via STING, which might be the molecular mechanism of Esketamine to ameliorate the MI caused by TQ-induced I/R injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00723-9.