Intensive Care Medicine Experimental最新文献

{"title":"Regional cerebral oxygen saturation during initial mobilization of critically ill patients is associated with clinical outcomes: a prospective observational study.","authors":"Ryota Imai, Takafumi Abe, Kentaro Iwata, Seigo Yamaguchi, Takeshi Kitai, Atsuhiro Tsubaki","doi":"10.1186/s40635-025-00722-2","DOIUrl":"https://doi.org/10.1186/s40635-025-00722-2","url":null,"abstract":"<p><strong>Background: </strong>Vital signs help determine the safety of early mobilization in critically ill patients in intensive care units. However, none of these variables directly assess cerebral circulation. Therefore, we aimed to investigate the relationship of regional cerebral oxygen saturation (rSO₂) and vital signs with in-hospital death in critically ill patients.</p><p><strong>Methods: </strong>This prospective study included critically ill patients admitted to the Uonuma Kikan Hospital Emergency Center who received physical therapy between June 2020 and December 2022. We continuously measured rSO₂ during the initial mobilization using a wearable brain near-infrared spectroscopy device. With in-hospital death as the primary endpoint, the association between rSO₂ and in-hospital death was assessed in Analysis 1 to determine the rSO₂ cut-off value that predicts in-hospital death. In Analysis 2, patients were categorised into survival and non-survival groups to examine the temporal changes in vital signs and rSO₂ associated with postural changes during mobilization.</p><p><strong>Results: </strong>Of the 132 eligible patients, 98 were included in Analysis 1, and 70 were included in Analysis 2. Analysis 1 demonstrated that lower premobilization rSO₂ was independently associated with in-hospital death (odds ratio 0.835, 95% confidence interval 0.724-0.961, p = 0.012). Receiver operating characteristic curve analysis identified an optimal rSO₂ cut-off value of 57% for predicting in-hospital death (area under the curve 0.818, sensitivity 73%, specificity 83%). Analysis 2 showed that rSO₂ changes during mobilization were unrelated to changes in vital signs, suggesting rSO₂ as an independent prognostic marker.</p><p><strong>Conclusions: </strong>The results suggest that rSO₂ measured during initial mobilization is associated with in-hospital death in critically ill patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"13"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dexmedetomidine alleviates acute kidney injury in a rat model of veno-arterial extracorporeal membrane oxygenation.","authors":"Min Yu, Shilin Wei, Xueyang Shen, Junjie Ying, Dezhi Mu, Xiangyang Wu, Yongnan Li","doi":"10.1186/s40635-025-00720-4","DOIUrl":"10.1186/s40635-025-00720-4","url":null,"abstract":"<p><strong>Background: </strong>Although extracorporeal membrane oxygenation (ECMO) is an effective technique for life support, the incidence of acute kidney injury (AKI) during ECMO support remains high. Dexmedetomidine (DEX), which has been widely used for sedation during ECMO, possesses several properties that help reduce the occurrence of AKI. This study aimed to investigate the protective effect of DEX on kidney function during ECMO.</p><p><strong>Methods: </strong>A total of 18 male Sprague-Dawley (SD) rats were randomly divided into three groups: Sham, ECMO, and ECMO + DEX groups. ECMO was established through the right jugular vein for venous drainage and right femoral artery for arterial infusion and lasts for four hours. Hematoxylin and eosin staining was used to evaluate the kidney Paller score for the rats in each group. Enzyme-linked immunosorbent assay was used to measure the levels of kidney injury biomarkers and cytokines in the serum. Reagent kits were used to measure the blood urea nitrogen (BUN) and creatinine (Cr) levels, which helped determine kidney function. Immunohistochemical staining was used to evaluate neutrophil infiltration in the kidney.</p><p><strong>Results: </strong>The pathological Paller score was substantially lower in the ECMO + DEX group. The levels of Kidney Injury Molecule-1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) were also significantly reduced. The kidney functionality, as indicated by BUN and Cr, was significantly improved compared with the ECMO group. The levels of cytokines IL-6, IL-1β, and TNF-α, were also significantly decreased in the ECMO + DEX group.</p><p><strong>Conclusion: </strong>This study demonstrated that dexmedetomidine could reduce inflammatory response and alleviate AKI during ECMO support.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"12"},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring timely and safe discharge from ICU: a comparative study of machine learning predictions and clinical practices.","authors":"Chao Ping Wu, Rachel Benish Shirley, Alex Milinovich, Kaiyin Liu, Eduardo Mireles-Cabodevila, Hassan Khouli, Abhijit Duggal, Anirban Bhattacharyya","doi":"10.1186/s40635-025-00717-z","DOIUrl":"10.1186/s40635-025-00717-z","url":null,"abstract":"<p><strong>Background: </strong>The discharge practices from the intensive care unit exhibit heterogeneity and the recognition of eligible patients for discharge is often delayed. Recognizing the importance of safe discharge, which aims to minimize readmission and mortality, we developed a dynamic machine-learning model. The model aims to accurately identify patients ready for discharge, offering a comparison of its effectiveness with physician decisions in terms of safety and discrepancies in discharge readiness assessment.</p><p><strong>Methods: </strong>This retrospective study uses data from patients in the medical ICU from 2015-to-2019 to develop ML models. The models were based on dynamic ICU-readily available features such as hourly vital signs, laboratory results, and interventions and were developed using various ML algorithms. The primary outcome was the hourly prediction of ICU discharge without readmission or death within 72 h post-discharge. These outcomes underwent subsequent validation within a distinct cohort from the year 2020. Additionally, the models' performance was assessed in comparison to physician judgments, with any discrepancies between the two carefully analyzed.</p><p><strong>Result: </strong>In the 2015-to-2019 cohort, the study included 17,852 unique ICU admissions. The LightGBM model outperformed other algorithms, achieving a AUROC of 0.91 (95%CI 0.9-0.91) and performance was held in the 2020 validation cohort (n = 509) with an AUROC of 0.85 (95%CI 0.84-0.85). The calibration result showed Brier score of 0.254 (95%CI 0.253-0.255). The physician agreed with the models' discharge-readiness prediction in 84.5% of patients. In patients discharged by physicians but not deemed ready by our model, the relative risk of 72-h post-ICU adverse outcomes was 2.32 (95% CI 1.1-4.9). Furthermore, the model predicted patients' readiness for discharge between 5 (IQR: 2-13.5) and 9 (IQR: 3-17) hours earlier in our selected thresholds.</p><p><strong>Conclusion: </strong>The study underscores the potential of ML models in predicting patient discharge readiness, mirroring physician behavior closely while identifying eligible patients earlier. It also highlights ML models can serve as a promising screening tool to enhance ICU discharge, presenting a pathway toward more efficient and reliable critical care decision-making.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"10"},"PeriodicalIF":2.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: the ups and downs of passive leg raising.","authors":"Rogério da Hora Passos, Fernanda Oliveira Coelho, Bruno Zawadzki","doi":"10.1186/s40635-025-00718-y","DOIUrl":"10.1186/s40635-025-00718-y","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"11"},"PeriodicalIF":2.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capillary refill time paradoxically decreases in a blood loss shock model.","authors":"Hugo Gustavsson, Frida Meyer, Sara Fahlander, Birgitta Ölwegård, Hanna Jonasson, Rani Toll, Joakim Henricson, Daniel Wilhelms","doi":"10.1186/s40635-025-00714-2","DOIUrl":"10.1186/s40635-025-00714-2","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate whether changes in capillary refill (CR) time precede macrovascular signs of deterioration in a human model of blood loss shock. The study was conducted at the Department of Emergency Medicine in Linköping, Sweden, and involved 42 healthy volunteers aged 18-45. Participants were randomized into two provocations of applied lower body negative pressure (LBNP): a stepwise escalation protocol and a direct application protocol, to simulate gradual and acute blood loss. The main outcome measure was CR time. Systolic, diastolic, and mean arterial pressures, heart rate, cardiac output, and systemic vascular resistance were measured continuously. CR time was assessed on the finger pulp using a standardized pressure and measured with a polarized reflectance imaging system.</p><p><strong>Results: </strong>The provocation elicited pre-syncope reactions and clear decrease in blood pressure for all participants, yet two-thirds of the participants in both protocols reacted with shorter CR times at maximum provocation, and the overall median CR time decreased by 0.2 s (Wilcoxon W = - 395.0, range: - 6.3 to 3.2, IQR - 1.3 to 0.1, P = 0.0070). Participants with shorter CR times exhibited comparatively greater increases in systemic vascular resistance and a more pronounced decrease in cardiac output.</p><p><strong>Conclusions: </strong>Our findings reveal that finger CR time paradoxically decreases in a majority of healthy volunteers in a lower body negative pressure model of blood loss, challenging traditional assumptions about the CR test's reliability as a shock indicator in its present interpretation.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"8"},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.","authors":"Jarrod L Thomas, Kirsty C McGee, Anower Hossain, Gavin D Perkins, Anthony C Gordon, Duncan Young, Danny McAuley, Mervyn Singer, Ranjit Lall, Tina Kramaric, Janet M Lord, Tony Whitehouse, Luis A J Mur","doi":"10.1186/s40635-024-00708-6","DOIUrl":"10.1186/s40635-024-00708-6","url":null,"abstract":"<p><strong>Purpose: </strong>The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers.</p><p><strong>Methods: </strong>Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect).</p><p><strong>Results: </strong>Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, L-tryptophan, L-alanine, 2,2,2-trichloroethanol, lactic acid and D-glucose.</p><p><strong>Conclusions: </strong>In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. D-Glucose, lactic acid, succinic acid, L-alanine, L-tryptophan and trichloroethanol were pathways that may merit further investigation.</p><p><strong>Trial registration: </strong>EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ).</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"9"},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis.","authors":"Golschan Asgarpur, Franz Weber, Peggy Kiessling, Nilufar Akbari, Fabian Stroben, Bernadette Kleikamp, Charlotte Kloft, Sascha Treskatsch, Stefan Angermair","doi":"10.1186/s40635-025-00716-0","DOIUrl":"10.1186/s40635-025-00716-0","url":null,"abstract":"<p><strong>Purpose: </strong>CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22). There is limited clinical data on the effect of CS on the plasma concentrations of beta-lactams. We aimed to evaluate the statistical and clinical impact of CS in a post-filter CKRT-CS setting on the plasma concentrations of the antibiotics meropenem and piperacillin in critically ill patients.</p><p><strong>Methods: </strong>Patients admitted to the intensive care unit (ICU) who received a prolonged infusion of piperacillin or meropenem with CS-combined CKRT were included in this retrospective analysis. TDM (therapeutic drug monitoring) plasma blood samples were collected at three different points. The differences in antibiotic concentrations between Pre, Intra, and Post were statistically compared to evaluate the total and isolated contributions of CKRT and CS to antibiotic removal. CS, CKRT and combined clearance (CL) values were calculated. The hypothesis was that the CS filter would have no clinically relevant impact on antibiotic levels.</p><p><strong>Results: </strong>207 TDM samples were taken from 24 critically ill patients requiring beta-lactam antibiotics. Among these, 129 were meropenem samples, and 78 were piperacillin samples. A decrease in both antibiotic levels was observed between Pre and Intra, and Pre and Post, and the median relative difference between was >15% (meropenem: Pre-Intra 34.8%, Pre-Post 35.8%; piperacillin: Pre-Intra 41.1%, Pre-Post 34.7%), indicating a statistically and clinically significant effect of CKRT on both antibiotic exposures. No significant difference was observed between Intra and Post indicating no clinically relevant drug removal via the CS filter. Changes in CL attributed to CS were minimal, with combined CL differing by ≤8.60% compared to CKRT clearance.</p><p><strong>Conclusion: </strong>The application of CS does not appear to significantly affect plasma concentrations of meropenem and piperacillin in critically ill patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"7"},"PeriodicalIF":2.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel lung imaging techniques: new experimental insights in acute respiratory failure.","authors":"Mariangela Pellegrini, Maurizio Cereda","doi":"10.1186/s40635-024-00711-x","DOIUrl":"https://doi.org/10.1186/s40635-024-00711-x","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"5"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A murine model of acute and prolonged abdominal sepsis, supported by intensive care, reveals time-dependent metabolic alterations in the heart.","authors":"Bart Jacobs, Inge Derese, Sarah Derde, Sarah Vander Perre, Lies Pauwels, Greet Van den Berghe, Jan Gunst, Lies Langouche","doi":"10.1186/s40635-025-00715-1","DOIUrl":"10.1186/s40635-025-00715-1","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced cardiomyopathy (SICM) often occurs in the acute phase of sepsis and is associated with increased mortality due to cardiac dysfunction. The pathogenesis remains poorly understood, and no specific treatments are available. Although SICM is considered reversible, emerging evidence suggests potential long-term sequelae. We hypothesized that metabolic and inflammatory cardiac changes, previously observed in acute sepsis as potential drivers of SICM, partially persist in prolonged sepsis.</p><p><strong>Methods: </strong>In 24-week-old C57BL/6J mice, sepsis was induced by cecal ligation and puncture, followed by intravenous fluid resuscitation, subcutaneous analgesics and antibiotics, and, in the prolonged phase, by parenteral nutrition. Mice were killed after 5 days of sepsis (prolonged sepsis, n = 15). For comparison, we included acutely septic mice killed at 30 h (acute sepsis, n = 15) and healthy controls animals (HC, n = 15). Cardiac tissue was collected for assessment of inflammatory and metabolic markers through gene expression, metabolomic analysis and histological assessment.</p><p><strong>Results: </strong>In prolonged sepsis, cardiac expression of IL-1β and IL-6 and macrophage infiltration remained upregulated (p ≤ 0.05). In contrast, tissue levels of Krebs cycle intermediates and adenosine phosphates were normal, whereas NADPH levels were low in prolonged sepsis (p ≤ 0.05). Gene expression of fatty acid transporters and of the glucose transporter Slc2a1 was upregulated in prolonged sepsis (p ≤ 0.01). Lipid staining and glycogen content were elevated in prolonged sepsis together with increased gene expression of enzymes responsible for lipogenesis and glycogen synthesis (p ≤ 0.05). Intermediate glycolytic metabolites (hexose-phosphates, GADP, DHAP) were elevated (p ≤ 0.05), but gene expression of several enzymes for glycolysis and mitochondrial oxidation of pyruvate, fatty-acyl-CoA and ketone bodies to acetyl-CoA were suppressed in prolonged sepsis (p ≤ 0.05). Key metabolic transcription factors PPARα and PGC-1α were downregulated in acute, but upregulated in prolonged, sepsis (p ≤ 0.05 for both). Ketone body concentrations were normal but ketolytic enzymes remained suppressed (p ≤ 0.05). Amino acid metabolism showed mild, mixed changes.</p><p><strong>Conclusions: </strong>Our results suggest myocardial lipid and glycogen accumulation and suppressed mitochondrial oxidation, with a functionally intact Krebs cycle, in the prolonged phase of sepsis, together with ongoing myocardial inflammation. Whether these alterations have functional consequences and predispose to long-term sequelae of SICM needs further research.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"6"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation into the influence of mild hypothermia on regulating ferroptosis through the P53-SLC7A11/GPX4 signaling pathway in sepsis-induced acute lung injury.","authors":"Liujun Tao, Jie Xu, Liangyan Jiang, Juntao Hu, Zhanhong Tang","doi":"10.1186/s40635-025-00713-3","DOIUrl":"10.1186/s40635-025-00713-3","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (S-ALI) significantly contributes to unfavorable clinical outcomes. Emerging evidence suggests a novel role for ferroptosis in the pathophysiology of ALI, though the precise mechanisms remain unclear. Mild hypothermia (32-34 °C) has been shown to inhibit inflammatory responses, reduce oxidative stress, and regulate metabolic processes. P53 has been reported to downregulate the transcriptional activity of solute carrier family 7 member 11 (SLC7A11), thereby limiting cystine uptake. This reduction in cystine availability compromises the activity of Glutathione peroxidase 4 (GPX4), a cystine-dependent enzyme, ultimately increasing cellular susceptibility to ferroptosis. However, it remains unclear whether mild hypothermia exerts protective effects through the P53-SLC7A11/GPX4 signaling pathway. This study investigates the influence of mild hypothermia on ferroptosis mediated by the P53-SLC7A11/GPX4 pathway in S-ALI.</p><p><strong>Methods: </strong>This study utilized both in vivo and in vitro models. In the vivo model, 64 Sprague-Dawley rats were employed, with 40 analyzed for survival outcomes. Sepsis was induced using the cecum ligation and puncture (CLP) method, after which rats were subjected to either normothermic (36-38 °C) or mild hypothermic (32-34 °C) conditions for a duration of 10 h. Twelve hours post-surgery, blood samples, bronchoalveolar lavage fluid, and lung tissue samples were harvested for histological analysis, measurement of inflammatory markers, wet/dry ratios, blood gas analysis, assessment of oxidative stress and ferroptosis, Western blotting, and RT-qPCR analysis. In the in vitro model, RLE-6TN cells were exposed to lipopolysaccharide (LPS) for 24 h under normothermic and mild hypothermic conditions. These cells were then evaluated for cell viability, inflammatory markers, oxidative stress levels, ferroptosis markers, as well as Western blot and RT-qPCR analyses.</p><p><strong>Results: </strong>CLP-induced sepsis led to elevated levels of inflammatory markers, increased lung injury scores, and heightened oxidative stress markers. These detrimental effects were significantly ameliorated by mild hypothermia. Furthermore, mild hypothermia reversed the modified expression of P53, SLC7A11, and GPX4 signaling molecules. Notably, mild hypothermia also improved the 5-day survival rate of CLP rats.</p><p><strong>Conclusion: </strong>Mild hypothermia attenuates S-ALI and modulates ferroptosis through the P53-SLC7A11/GPX4 signaling pathway.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"4"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}