Intensive Care Medicine Experimental最新文献

{"title":"Tranexamic acid did not attenuate the acute rise in plasma syndecan-1 in a severely injured cohort: a laboratory analysis of the PATCH clinical trial.","authors":"Elissa M Milford, Dusan Marjanovic, Heidi Ho, Steven Wallis, Dominik F Draxler, Biswadev Mitra, Russell L Gruen, Robert Medcalf, Stephen Bernard, Colin McArthur, Marc Meagele, Brian Burns, Dashiell Gantner, Michael C Reade","doi":"10.1186/s40635-025-00784-2","DOIUrl":"10.1186/s40635-025-00784-2","url":null,"abstract":"<p><strong>Background: </strong>Injury to the vascular endothelium occurs in up to 34% of patients acutely following severe traumatic injury and can be quantified clinically by measuring the plasma concentration of syndecan-1 (SDC-1). Tranexamic acid (TXA) attenuates endothelial damage in animal and cell culture models and has been associated with lower SDC-1 levels after prehospital TXA administration. The aim of this study was to assess the association of prehospital TXA on SDC-1 levels in a more severely injured prehospital cohort.</p><p><strong>Methods: </strong>The PATCH-Trauma trial randomised patients to receive pre-hospital TXA or placebo. In this sub-cohort, SDC-1 was measured in blood samples collected on hospital admission, at 8 and 24 h. Relationships between SDC-1 levels over time, treatment groups, and outcomes were analyzed using regression modelling controlling for potential confounding factors.</p><p><strong>Results: </strong>There were 89 patients included, with 57 administered TXA and 32 administered placebo (per protocol). SDC-1 levels were available in 87 patients on arrival to hospital, 70 at 8 h, and 69 at 24 h. Patients had a median SDC-1 on admission of 106 ng/mL (IQR 88-137). There was no effect of TXA treatment on SDC-1 levels over the first 24 h of hospital admission, even after controlling for known confounders. There was no association between SDC-1 level at any time point and the development of deep vein thrombosis or sepsis, mortality at 28-days, or days alive and out of hospital, even after adjustment for confounding factors.</p><p><strong>Conclusion: </strong>Administration of TXA, initiated pre-hospital, did not affect SDC-1 levels in the first 24 h of hospital admission in this severely injured cohort. Further research is required to elucidate the mechanisms of the effect of TXA on the endothelium as well as the utility of SDC-1 as an endothelial biomarker.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"72"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608288","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":"Recruitment of renal functional reserve by intravenous amino acid loading in a sheep model of cardiopulmonary bypass.","authors":"Taku Furukawa, Alemayehu H Jufar, Clive N May, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Sally G Hood, Ian E Birchall, Jaishankar Raman, Pei Chen Connie Ow, Anton Trask-Marino, Lachlan F Miles, Rinaldo Bellomo, Yugeesh R Lankadeva","doi":"10.1186/s40635-025-00774-4","DOIUrl":"10.1186/s40635-025-00774-4","url":null,"abstract":"<p><strong>Background: </strong>Cardiopulmonary bypass (CPB) may decrease the renal functional reserve (RFR). However, the temporal changes in RFR after during the recovery period after CPB remains unknown. We assessed RFR before and then weekly after CPB over four weeks following CPB in non-anaesthetised sheep.</p><p><strong>Methods: </strong>In 10 Merino ewes, amino acids were infused before CPB and weekly for four weeks to assess RFR. At each assessment, we measured renal blood flow (RBF), renal oxygen delivery (RDO₂), creatinine clearance and medullary and cortical oxygenation. Histological assessment was performed at 4 weeks.</p><p><strong>Results: </strong>Before CPB, amino acid infusion increased RBF from (mean ± SD) 6.60 ± 1.64 to 8.56 ± 1.80 mL/kg/min, and RDO₂ from 0.80 ± 0.28 to 1.12 ± 0.37 mL O₂/kg/min. These renal macro-circulatory responses remained consistent across all weekly assessments after CPB. Amino acid infusion also increased creatinine clearance (from 62.5 ± 15.0 to 110 ± 30.6 mL/h pre-CPB) throughout the study period. RFR remained unchanged over time (P = 0.53). However, compared with pre-CPB values, medullary (33.9 ± 9.0 pre-CPB to 15.1 ± 13.2 mmHg at 4 weeks, P = 0.0068) and cortical tissue PO₂ (46.0 ± 14.2 to 17.2 ± 6.5 mmHg, P = 0.0029) decreased over time. Furthermore, the response of the medullary (but not cortical) PO₂ to amino acid infusion changed over time (P = 0.0064). While medullary PO₂ did not change in response to amino acid infusion pre-CPB and at one week after CPB, it appeared to fall from two weeks thereafter (P = 0.039 and 0.091 at weeks 2 and 3, respectively). Despite preserved RFR, sheep exposed to CPB showed greater peritubular inflammation, interstitial fibrosis and tubular casts compared with healthy controls (P = 0.007, 0.021, 0.007, respectively).</p><p><strong>Conclusions: </strong>In this large mammalian model of CPB, weekly amino acid administration consistently recruited RFR over four weeks, despite the presence of histological injury. However, it was associated with the development of renal medullary hypoxia after two weeks. These findings highlight the complexity of the pathophysiological response of the kidney to CPB.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"71"},"PeriodicalIF":2.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600327","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":"Immunobiological effects of tocilizumab across respiratory subphenotypes in COVID-19 ARDS.","authors":"Emma Rademaker, Daan F L Filippini, Jelle L G Haitsma Mulier, Marleen A Slim, Rombout B E van Amstel, Sivasubramanium V Bhavani, Nicole P Juffermans, Harm-Jan S de Grooth, Lennie P G Derde, Olaf L Cremer, Lieuwe D J Bos","doi":"10.1186/s40635-025-00779-z","DOIUrl":"10.1186/s40635-025-00779-z","url":null,"abstract":"<p><strong>Background: </strong>Two distinct longitudinal respiratory subphenotypes have recently been described in COVID-19-related acute respiratory distress syndrome (ARDS). These subphenotypes exhibit dynamic immunobiological changes that may help guide immunomodulatory interventions. However, the extent to which the immune response is determined by respiratory subphenotype in the presence of concurrent immunomodulatory treatment remains unclear. We investigated the independent and combined effects of respiratory subphenotype and tocilizumab on inflammatory response and clinical outcomes.</p><p><strong>Methods: </strong>We analyzed patients from existing COVID-19 biobanks who were consecutively admitted to the ICU and received more than 4 days of invasive mechanical ventilation between March 2020 and May 2022. Patients were classified into two previously described longitudinal respiratory subphenotypes-characterized by mechanical power, minute volume and ventilatory ratio-referred to as 'low-power' and 'high-power' subphenotypes. We analyzed how tocilizumab treatment and respiratory subphenotype were associated with endothelial and inflammatory plasma biomarkers on days 0, 4 and 7, as well as with mortality.</p><p><strong>Results: </strong>720 patients were included, of whom 464 (64%) and 256 (36%) were assigned to the low- and high-power subphenotypes, respectively. 108 (23%) of the low-power subphenotype patients received tocilizumab, and 43 (17%) of the high-power subphenotype. 427 patients had plasma samples available. The high-power subphenotype was associated with slightly higher SP-D, thrombomodulin and TNF-RI plasma concentrations on the day of intubation compared to the low-power subphenotype, along with a more rapid increase in IL-6 and TNF-RI levels in subjects who had received tocilizumab treatment (β = 0.14 log ng/ml, p = 0.022, and β = 0.06 log ng/ml, p = 0.014, respectively). Tocilizumab treatment accounted for four times more variance in IL-6 and angiopoietin-2 levels than subphenotype, while subphenotype explained only a small proportion of the variance and slightly more than tocilizumab for TNF-RI and thrombomodulin. Subphenotype did not modify the association between tocilizumab and mortality (IPTW adjusted hazard ratio 1.18; 95%CI 0.60-2.33).</p><p><strong>Conclusion: </strong>Respiratory subphenotypes showed varying TNF-RI and IL-6 responses to tocilizumab, but these differences were only minor compared to the drug's overall immunobiological effect. This suggests that respiratory subphenotype should not determine tocilizumab treatment decisions.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"70"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591107","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":"Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients.","authors":"L Felipe Damiani, Roque Basoalto, Vanessa Oviedo, Leyla Alegria, Dagoberto Soto, M Consuelo Bachmann, Yorschua Jalil, Cesar Santis, David Carpio, Rodrigo Ulloa, Daniel Valenzuela, Magdalena Vera, Marcus J Schultz, Jaime Retamal, Alejandro Bruhn, Guillermo Bugedo","doi":"10.1186/s40635-025-00782-4","DOIUrl":"10.1186/s40635-025-00782-4","url":null,"abstract":"<p><strong>Background: </strong>The respiratory rate (RR) is a key determinant of the mechanical power of ventilation (MP). The effect of reducing the RR on MP and its potential to mitigate ventilator-induced lung injury remains unclear.</p><p><strong>Objectives: </strong>To compare invasive ventilation using a lower versus a higher RR with respect to MP and plasma biomarkers of lung injury in COVID-19 ARDS patients.</p><p><strong>Methods: </strong>In a randomized cross-over clinical study in COVID-19 ARDS patients, we compared ventilation using a lower versus a higher RR in time blocks of 12 h. Patients were ventilated with tidal volumes of 6 ml/kg predicted body weight, and positive-end-expiratory pressure and fraction of inspired oxygen according to an ARDS network table. Respiratory mechanics and hemodynamics were assessed at the end of each period, and blood samples were drawn for measurements of inflammatory cytokines, epithelial and endothelial lung injury markers. In a subgroup of patients, we performed echocardiography and esophageal pressure measurements.</p><p><strong>Results: </strong>We enrolled a total of 32 patients (26 males [81%], aged 52 [44-64] years). The median respiratory rate during ventilation with a lower and a higher RR was 20 [16-22] vs. 30 [26-32] breaths/min (p < 0.001), associated with a lower median minute ventilation (7.3 [6.5-8.5] vs. 11.6 [10-13] L/min [p < 0.001]) and a lower median MP (15 [11-18] vs. 25 [21-32] J/min [p < 0.001]). No differences were observed in any inflammatory (IL-6, IL-8, and TNF-R1), epithelial (s-RAGE and SP-D), endothelial (Angiopoietin-2), or pro-fibrotic activity (TGF-ß) marker between high or low RR. Cardiac function by echocardiography, and respiratory mechanics using esophageal pressure measurements were also not different.</p><p><strong>Conclusions: </strong>Reducing the respiratory rate decreases mechanical power in COVID-19 ARDS patients but does not reduce plasma lung injury biomarkers levels in this cross-over study. Study registration This study is registered at clinicaltrials.gov (study identifier NCT04641897).</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"69"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591195","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":"What can the machine teach us?","authors":"Edward J Schenck","doi":"10.1186/s40635-025-00775-3","DOIUrl":"10.1186/s40635-025-00775-3","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"68"},"PeriodicalIF":2.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575387","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":"29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial.","authors":"Evdoxia Kyriazopoulou, Antigone Kotsaki, Asimina Safarika, Garyfallia Poulakou, Haralampos Milionis, Simeon Metallidis, Georgios Adamis, Archontoula Fragkou, Aggeliki Rapti, Pierluigi Del Vecchio, Ioannis Kalomenidis, Danae Kitzoglou, Andrea Angheben, Ilias Kainis, Konstantina Iliopoulou, Francesco Saverio Serino, Petros Bakakos, Vassiliki Tzavara, Sofia Ioannou, Lorenzo Dagna, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Matteo Bassetti, Vasileios Kotsis, George Tsoukalas, Carlo Selmi, Sofia Nikolakopoulou, Michael Samarkos, Michael Doumas, Aikaterini Masgala, Ilias Papanikolaou, Aikaterini Argyraki, Karolina Akinosoglou, Styliani Symbardi, Periklis Panagopoulos, George N Dalekos, Oliver Liesenfeld, Timothy E Sweeney, Purvesh Khatri, Evangelos J Giamarellos-Bourboulis","doi":"10.1186/s40635-025-00777-1","DOIUrl":"10.1186/s40635-025-00777-1","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers based on host response signatures are currently under development for the critically ill. We applied a 29-mRNA classifier for the diagnosis and prognosis of suspected acute infection and sepsis (TriVerity^™, Inflammatix Inc.) in patients hospitalized with COVID-19.</p><p><strong>Methods: </strong>We applied three scores from locked classifiers (IMX-BVN-4 and IMX-SEV-4) from the 29-mRNA TriVerity^™ blood test in participants of the SAVE-MORE randomized clinical trial (ClinicalTrials.gov NCT04680949) at baseline and days 4 and 7 of treatment, to classify bacterial infection, viral infection and decompensation. Participants were adults hospitalized with confirmed COVID-19 pneumonia and plasma soluble urokinase plasminogen activator receptor (suPAR) levels of ≥ 6 ng/ml, randomized to placebo or anakinra treatment.</p><p><strong>Results: </strong>A total of 471 patients were studied. At baseline nearly 90% had a Very Low or Low IMX-BVN-4 Bacterial Score and Moderate, High or Very High IMX-BVN-4 Viral Score. Anakinra treatment had an effect on the expression of genes indicating IMX-SEV-4 High or Very High scores after a 7 day treatment compared to baseline (12.9% of anakinra-treated patients continued being classified as high severity vs 20.4% of placebo-treated patients, p 0.046).</p><p><strong>Conclusions: </strong>The classifiers were well tested in COVID-19 pneumonia and may become a useful tool for hospitalized patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"67"},"PeriodicalIF":2.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527827","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":"Digital twins suggest a mechanistic basis for differing responses to increased flow rates during high-flow nasal cannula therapy.","authors":"Hossein Shamohammadi, Sina Saffaran, Roberto Tonelli, Valentina Chiavieri, Giacomo Grasselli, Enrico Clini, Tommaso Mauri, Declan G Bates","doi":"10.1186/s40635-025-00773-5","DOIUrl":"10.1186/s40635-025-00773-5","url":null,"abstract":"<p><strong>Background: </strong>Inconsistent responses to increased flow rates have been observed in patients with acute hypoxemic respiratory failure (AHRF) treated with high-flow nasal cannula (HFNC) therapy, with a significant minority in two recent studies exhibiting increased respiratory effort at higher flow rates. Digital twins of patients receiving HFNC could help understand the physiological basis for differing responses.</p><p><strong>Methods: </strong>Patient data were collated from previous studies in AHRF patients who were continuously monitored with electrical impedance tomography and oesophageal manometry and received HFNC at flow rates of 30, 40 or 45 L/min. Patients, based on their responses to an increase in flow rate to 60 L/min, were categorised into two groups: five responders with reduced oesophageal pressure swings ΔP_es (- 3.1 cmH₂O on average), and five non-responders with increased ΔP_es (+ 2.0 cmH₂O on average). Two cohorts of digital twins were created based on these data using a multi-compartmental mechanistic cardiopulmonary simulator. Digital twins' responses to increased HFNC flow rates (60 L/min) were simulated with constant respiratory effort to assess changes in gas exchange and lung mechanics, and with varying respiratory effort to quantify their combined effects on lung mechanics and P-SILI indicators.</p><p><strong>Results: </strong>The digital twins accurately replicated patient-specific responses at all flow rates. Responder digital twins showed a mean 20 mL/cmH₂O increase in lung compliance at higher flow rates, versus a 6 mL/cmH₂O decrease in compliance with non-responders. In digital twins of responders versus non-responders, increased flow rates produced a mean change in lung stress of - 1.5 versus + 1.2 cmH₂O, in dynamic lung strain of - 8.8 versus + 16.4%, in driving pressure of - 1.3 versus + 1.1 cmH₂O, and in mechanical power of - 0.8 versus + 1.2 J/min. Higher flow rate dependent positive end-expiratory pressure in digital twins of non-responders did not cause recruitment, and reduced tidal volumes due to higher functional residual capacities-to compensate for the resulting worsened gas-exchange, non-responders increased their respiratory effort, in turn increasing patient self-inflicted lung injury (P-SILI) indicators. In digital twins of responders, reductions in tidal volumes due to higher FRCs resulting from increased PEEP were outweighed by alveolar recruitment. This increased compliance and improved gas exchange, permitting reduced respiratory effort and decreases in P-SILI indicators.</p><p><strong>Conclusions: </strong>Failure to reduce spontaneous respiratory efforts in response to increased HFNC flow rates could be due to a deterioration in lung mechanics, with an attendant risk of P-SILI.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"66"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505641","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":"Animal models of critical care illnesses: current reality, future directions.","authors":"John F Fraser, Shigeaki Inoue, Yongming Yao, Marcin F Osuchowski","doi":"10.1186/s40635-025-00776-2","DOIUrl":"10.1186/s40635-025-00776-2","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"65"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484291","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":"Citrate regional anticoagulation of 500 ml/min of extracorporeal blood flow: an experimental study.","authors":"Sebastiano Maria Colombo, Luigi Vivona, Michele Battistin, Vittorio Scaravilli, Alessandro Galli, Chiara Anzanello, Elisa Cipriani, Francesca Gori, Serena Todaro, Carlo Valsecchi, Daniele Dondossola, Anna Paola Marcello, Andrea Carlin, Antonio Pesenti, Giacomo Grasselli, Alberto Zanella","doi":"10.1186/s40635-025-00771-7","DOIUrl":"10.1186/s40635-025-00771-7","url":null,"abstract":"<p><strong>Background: </strong>Regional citrate anticoagulation (RCA) is the most widespread technique which allows to perform extracorporeal treatments, avoiding the complications of systemic anticoagulation. Due to limited citrate clearance, RCA may be applied only to low extracorporeal blood flows (i.e., BF < 200 ml/min). In this proof of concept study, we developed an innovative RCA technique based on Ion Exchange Resin (i-ER) technology capable of regionally anticoagulating BF up to 500 mL/min.</p><p><strong>Methods: </strong>Six healthy swine (41.0 ± 3.1 kg) were sedated, mechanically ventilated, and connected to a prototype extracorporeal circuit for continuous renal replacement therapy featuring a citrate-removal stage based on absorbent materials and replacement fluids. Blood flow was 500 ml/min. Sodium citrate was continuously infused at the circuit inlet (5 mmol/L). Heparin was continuously infused. Citrate concentration and Kaolin Heparinase thromboelastography (KH-TEG) were measured on arterial blood, extracorporeal blood downstream the citrate infusion port, and downstream the citrate-removal stage. Samples were collected at baseline, 2, 8, 15, 30, 45, 60, 90, and 120 min for citrate and at baseline, 2, 30, 60, and 120 min for KH-TEG. Calcium chloride was infused to maintain systemic ionized calcium within the physiological range. The experiment lasted 2 h.</p><p><strong>Results: </strong>During the whole experiment, KH-TEG in the artery showed normal coagulation: reaction time (R) was 8.30[6.80-10.10] min, with Maximum Amplitude (MA) of 71.70[67.90-77.00] mm, while in the extracorporeal circuit, KH-TEG showed no sign of clot formation R > 60 min, MA = 0 mm. Citrate concentrations in blood samples were stable within 30 min, then slowly increased. The efficacy of the citrate-removal dropped from 93.8 ± 3.4% to 48.3 ± 1.5% at the beginning (2 min) and at the end (2 h), respectively (p < 0.001), due to loss of efficiency of the iERs.</p><p><strong>Conclusions: </strong>This study demonstrates that iER-based RCA is a feasible and effective technique for regional anticoagulation of extracorporeal blood flow up to 500 mL/min for 60 min without significant complications.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"64"},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475110","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":"Physiology, imaging and proteomics of non-ventilated vs. non-perfused lung injury: an experimental study.","authors":"Anna Damia, Ines Marongiu, Elena Spinelli, Francesco Damarco, Clarissa Uslenghi, Giovanni Lorenzo Rumi, Michele Battistin, Caterina Lonati, Alessandra Maria Storaci, Gianluca Lopez, Maria Rosaria De Filippo, Fabiana Madotto, Cristina Banfi, Alice Mallia, Lorenzo Rosso, Valentina Vaira, Tommaso Mauri","doi":"10.1186/s40635-025-00772-6","DOIUrl":"10.1186/s40635-025-00772-6","url":null,"abstract":"<p><strong>Background: </strong>The exclusion of one lung from ventilation or pulmonary artery perfusion triggers pathological mechanisms that can lead to lung injury. Although the final effect is similar for both insults, the underlying mechanisms may differ. Primary aim of this study was to compare severity of lung injury between non-ventilated (NVLI) and non-perfused (NPLI) lung injury. Secondary aims were to compare physiologic, imaging and proteomic signatures of NVLI vs NPLI.</p><p><strong>Methods: </strong>Sedated and paralyzed healthy female piglets (weight = 36 ± 5 kg) were mechanically ventilated for 24 h after left pulmonary artery ligation (NPLI group, n = 11) or exclusion from ventilation of the left lung (NVLI group, n = 10). Physiological data including electrical impedance tomography imaging of regional ventilation and perfusion were collected. Histological scoring was performed blindly as well as proteomic analysis of broncho-alveolar lavage (BAL) fluids and lung tissue samples at the end of the experiment.</p><p><strong>Results: </strong>The left lung of both groups received similarly low fraction (< 20%) of blood flow. The left side of the NPLI group was characterized by ventilation distributed only to the dead space and high ventilation/perfusion compartments, while the left lung of the NVLI group was characterized by perfusion only to the shunt compartment. The left lung of the NVLI group showed severe pulmonary vascular dysfunction (pulmonary vascular resistance > 2000 dyne/s/cm^-5), while the left lung of the NPLI group was ventilated with raising inspiratory stress (driving pressure > 20 cmH₂O at the end of the experiment and progressive decline in left lung compliance). The histologic lung injury score was higher for the left lung of the NVLI group compared to the left lung of the NPLI (left histological score: 10.3 ± 2.0 vs 6.4 ± 1.6, p < 0.0001), and pro-inflammatory alveolar cytokines were similarly more expressed in the left lung of the NVLI versus NPLI group (IL-1β: 418 ± 416 vs 53 ± 71, p < 0.001; IL-6: 406 ± 455 vs 99 ± 93, p = 0.036). Proteomic analysis showed signature specific for the two injuries, with two proteins, namely PRDX5 and DCTN1, being upregulated in NVLI left lung compared with the left NPLI lung. The right lung developed injury only in the NVLI group (right histological score: 5.5 ± 1.9 vs 3.0 ± 0.7, p < 0.001).</p><p><strong>Conclusions: </strong>Lung injury is more severe in terms of lung histological score in the collapsed lung of the NVLI group and involves also contralateral areas. At the mechanistic level, NVLI has specific physiologic mechanisms like vascular dysfunction and inflammation and presents unique proteomic profile in comparison to NPLI.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475111","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}