cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. dexmedetomidine (dex), a α2-adrenergic receptor (α2-ar) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YoH), an α2-AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin-I (TN-I), interleukin 6 (IL-6), superoxide dismutase (SOD), malonaldehyde (Mda) and glutathione (GSH) levels, and iron release. Ferroptosis-targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN-I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of Mda, 8-hydroxy-2'-deoxyguanosine and the inflammatory factors IL-6 and monocyte chemoattractant protein-1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, clP increased expression levels of heme oxygenase-1 (Ho-1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of dex (clP + dex + YoH vs. clP + dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis-induced Ho-1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis-induced myocardial cellular injury.

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Introduction: Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. Methods: This study was a retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC) III database, which includes more than 1,000,000 SBP records from 12,820 patients. Associations of cumulative times at four SBP ranges (<100 mm Hg, 100-120 mm Hg, 120-140 mm Hg, and 140 mm Hg) with mortality (12-, 3-, 1-month mortality and in-hospital mortality) were evaluated. Restricted cubic splines and multivariable Cox regression models were employed to assess associations between mortality and cumulative times at SBP levels (4 levels: <2, 2-12, 12-36, and 36 h) over 72 h of ICU admission. Additionally, 120 mm Hg to 140 mm Hg was subdivided into <12 h (Group L) and 12 h (Group M) subsets and subjected to propensity-score matching and subgroup analyses. Results: At 120 mm Hg to 140 mm Hg, level-4 SBP was associated with lower adjusted risks of mortality at 12 months (OR, 0.71; CI, 0.61-0.81), 3 months (OR, 0.72; CI, 0.61-0.85), and 1 month (OR, 0.61; CI, 0.48-0.79) and in the hospital (OR, 0.71; CI, 0.58-0.88) than level-1 SBP. The cumulative times at the other 3 SBP ranges (<100 mm Hg, 100-120 mm Hg, and 140 mm Hg) were not independent risk predictors of prognosis. Furthermore, Group M had lower 12-month mortality than Group L, which remained in the propensity-score matched and subgroup analyses. Conclusions: SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.