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BACKGROUND: The effectiveness of aspirin treatment in septic patients remains a subject of debates. OBJECTIVE: To explore the association between aspirin usage and the prognosis of patients with sepsis-induced myocardial injury (SIMI), as well as the timing of aspirin administration. METHODS: Patients with SIMI were screened in the MIMIC-IV database and categorized into aspirin and non-aspirin groups based on their medications during intensive care unit (ICU) stay, and propensity matching analysis (PSM) was subsequently performed to reduce bias at baseline between the groups. The primary outcome was 28-day all-cause mortality. Cox multivariate regression analysis was conducted to evaluate the impact of aspirin on the prognosis of patients with SIMI. RESULTS: The pre-PSM and post-PSM cohorts included 1170 and 1055 patients, respectively. In the pre-PSM cohort, the aspirin group is older, has a higher proportion of chronic comorbidities, and lower SOFA and SAPS II scores when compared to the non-aspirin group. In the PSM analysis, most of the baseline characterization biases were corrected, and aspirin use was also associated with lower 28-day mortality (hazard ratio [HR] = 0.51, 95 % confidence interval [CI]: 0.42-0.63, P < 0.001), 90-day mortality (HR = 0.58, 95 % CI: 0.49-0.69, P < 0.001) and 1-year mortality (HR = 0.65, 95 % CI: 0.56-0.76, P < 0.001), irrespective of aspirin administration timing. A sensitivity analysis based on the original cohort confirmed the robustness of the findings. Additionally, subsequent subgroup analysis revealed that the use of vasopressin have a significant interaction with aspirin's efficacy. CONCLUSION: Aspirin was associated with decreased mortality in SIMI patients, and this beneficial effect persisted regardless of pre-ICU treatment.
RESUMO
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte's programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.
RESUMO
OBJECTIVE: To investigate the therapeutic effect of Buyang huanwu decoction (BYHWD) on sepsis-induced myocardial injury (SIMI) and explore the mechanism by which BYHWD mitigates SIMI. METHODS: The Lipopolysaccharide (LPS)-induced SIMI mouse model was established to detect the effect of BYHWD-low (1 mg/kg), BYHWD-middle (5 mg/kg), and BYWHD-high (20 mg/kg) on SIMI. The survival of these BYHWD-treated septic mice was investigated. The histology of myocardial tissues was determined by hematoxylin and eosin (H&E) staining. The apoptotic index and inflamed microenvironment of myocardial tissues were assessed by immunofluorescent staining (IF) and flow cytometry analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to determine the key chemical components in the serum of BYHWD-loaded septic mice. Immunoblotting assay was utilized to detect NF-κB and TGF-ß signaling activity, and M1/M2-macrophage markers using RAW264.7 cells. RESULTS: The high dosage of BYHWD (BYHWD-high, 20 mg/Kg) significantly attenuated SIMI and improved the survival of septic mice. The BYHWD-high solution markedly reduced myocardial cell apoptosis and mitigated the inflamed microenvironment by suppressing CD45+ immune cell infiltration. Importantly, BYHWD decreased macrophage accumulation and promoted an M2-macrophage polarization. Paeoniflorin (PF) and calycosin-7-O-ß-glucoside (CBG) were identified as the key molecules in BYWHD with therapeutic effect. PF (10 µM) and CBG (1 µM) inhibited NF-κB signaling, meanwhile they upregulated the TGF-ß pathway, thereby facilitating an M2-macrophage phenotypic transition in RAW264.7 cells. CONCLUSIONS: BYHWD, with two effective components PF and CBG, can mitigate SIMI by suppressing the inflamed myocardial microenvironment and skewing an immunosuppressive M2-macrophage phenotype.