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A study of structural changes in lung tissue during the formation of organ edema due to inhalation of a lipotropic poison, carbonic acid dichloride, showed the peculiarities of the formation of acute respiratory distress syndrome. The point of application of the poison is the distal bronchioles, whose epithelium is subject to dystrophic and necrotic changes followed by goblet metaplasia. The absorbed poison causes pronounced changes in blood microcirculation, steroid-resistant NO-mediated endothelial dysfunction with blood deposition in dilated capillaries, aggregation, and lysis of erythrocytes. Changes in the vascular bed in the interalveolar septa precede the formation of an acute inflammatory reaction with the accumulation of alveolar effusion and dystrophic changes in the alveolar epithelium with cell desquamation. Among the cells of the alveolar lining, type II alveolocytes are the most vulnerable. Plasma permeation of the connective tissue of the interalveolar septa interstitium is accompanied by their infiltration with polymorphonuclear leukocytes and activation of macrophages. Desquamation of epithelial cells of the distal bronchioles leads to obstruction of their lumens and, through the valve mechanism, contributes to overextension of the alveoli with the formation of emphysema and reduction of capillary blood circulation in the alveolar septa. The observed changes determined the directions for improving the treatment of poisoning by asphyxiating poisons. [ABSTRACT FROM AUTHOR]

Background: Quantification of pulmonary edema in patients with acute respiratory distress syndrome (ARDS) by chest computed tomography (CT) scan has not been validated in routine diagnostics due to its complexity and time-consuming nature. Therefore, the single-indicator transpulmonary thermodilution (TPTD) technique to measure extravascular lung water (EVLW) has been used in the clinical setting. Advances in artificial intelligence (AI) have now enabled CT images of inhomogeneous lungs to be segmented automatically by an intensive care physician with no prior radiology training within a relatively short time. Nevertheless, there is a paucity of data validating the quantification of pulmonary edema using automated lung segmentation on CT compared with TPTD. Methods: A retrospective study (January 2016 to December 2021) analyzed patients with ARDS, admitted to the intensive care unit of the Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, who underwent a chest CT scan and hemodynamic monitoring using TPTD at the same time. Pulmonary edema was estimated using manually and automated lung segmentation on CT and then compared to the pulmonary edema calculated from EVLW determined using TPTD. Results: 145 comparative measurements of pulmonary edema with TPTD and CT were included in the study. Estimating pulmonary edema using either automated lung segmentation on CT or TPTD showed a low bias overall (− 104 ml) but wide levels of agreement (upper: 936 ml, lower: − 1144 ml). In 13% of the analyzed CT scans, the agreement between the segmentation of the AI algorithm and a dedicated investigator was poor. Manual segmentation and automated segmentation adjusted for contrast agent did not improve the agreement levels. Conclusions: Automated lung segmentation on CT can be considered an unbiased but imprecise measurement of pulmonary edema in mechanically ventilated patients with ARDS. [ABSTRACT FROM AUTHOR]

Background: Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods: This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results: Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions: The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources. [ABSTRACT FROM AUTHOR]

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE. [ABSTRACT FROM AUTHOR]

This narrative review delves into the intricate interplay between the lungs and the kidneys, with a focus on elucidating the pathogenesis of diseases influenced by immunological factors, acid–base regulation, and blood gas disturbances, as well as assessing the effects of various therapeutic modalities on these interactions. Key disorders, such as anti-glomerular basement membrane (anti-GBM) disease, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Anti-neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV), are also examined to shed light on their underlying mechanisms. This review also explores the relationship between acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), emphasizing how inflammatory mediators can lead to systemic damage and impact multiple organs. In ARDS, fluid overload exacerbates pulmonary edema, while imbalances in blood volume, such as hypovolemia or hypervolemia, can precipitate renal dysfunction. The review highlights how mechanical ventilation strategies can compromise renal blood flow, trigger systemic inflammation, and induce hemodynamic and neurohormonal alterations, all contributing to lung and kidney damage. The impact of extracorporeal membrane oxygenation (ECMO) on lung–kidney interactions is evaluated, highlighting its role in severe respiratory failure and its renal implications. Emerging therapies, such as mesenchymal stem cells and extracellular vesicles, are discussed as promising avenues to mitigate organ damage and enhance outcomes in critically ill patients. Overall, this review offers a nuanced exploration of lung–kidney dynamics, bridging historical insights with contemporary perspectives. It underscores the clinical significance of these interactions in critically ill patients and advocates for integrated management approaches to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES). Results: Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44–5.25] vs. 5.33 [5.06–6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41–4.75] vs. 4.51 [4.47–4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1–7] vs. 14 [12–16] vessels per recording, p = 0.008; HES: 4 [2–6] vs. 12 [10–13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1–9] vs. HES: 1 [0–4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0–5.0] mL vs. 9 [4.5–10.0], p < 0.001) and phenylephrine (20 [0–40] µg vs. 90 [40–200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13–25] vs. 33 [24–51] ng/mL, p = 0.006), interleukin-10 (434 [295–782] vs. 2120 [1309–3408] pg/ml, p < 0.0001), syndecan-1 (5 [3–7] vs. 15 [11–16] ng/mL, p < 0.001) and NGAL (555 [375–1078] vs. 2200 [835–3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES. Conclusion: CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming. [ABSTRACT FROM AUTHOR]

Background: Haemoglobin variation (ΔHb) induced by fluid transfer through the intestitium has been proposed as a useful tool for detecting hydrostatic pulmonary oedema (HPO). However, its use in the emergency department (ED) setting still needs to be determined. Methods: In this observational retrospective monocentric study, ED patients admitted for acute dyspnoea were enrolled. Hb values were recorded both at ED presentation (T0) and after 4 to 8 h (T1). ΔHb between T1 and T0 (ΔHbT1-T0) was calculated as absolute and relative value. Two investigators, unaware of Hb values, defined the cause of dyspnoea as HPO and non-HPO. ΔHbT1-T0 ability to detect HPO was evaluated. A machine learning approach was used to develop a predictive tool for HPO, by considering the ability of ΔHb as covariate, together with baseline patient characteristics. Results: Seven-hundred-and-six dyspnoeic patients (203 HPO and 503 non-HPO) were enrolled over 19 months. Hb levels were significantly different between HPO and non-HPO patients both at T0 and T1 (p < 0.001). ΔHbT1-T0 were more pronounced in HPO than non-HPO patients, both as relative (-8.2 [-11.2 to -5.6] vs. 0.6 [-2.1 to 3.3] %) and absolute (-1.0 [-1.4 to -0.8] vs. 0.1 [-0.3 to 0.4] g/dL) values (p < 0.001). A relative ΔHbT1-T0 of -5% detected HPO with an area under the receiver operating characteristic curve (AUROC) of 0.901 [0.896–0.906]. Among the considered models, Gradient Boosting Machine showed excellent predictive ability in identifying HPO patients and was used to create a web-based application. ΔHbT1-T0 was confirmed as the most important covariate for HPO prediction. Conclusions: ΔHbT1-T0 in patients admitted for acute dyspnoea reliably identifies HPO in the ED setting. The machine learning predictive tool may represent a performing and clinically handy tool for confirming HPO. [ABSTRACT FROM AUTHOR]

Heart–lungs interactions are related to the interplay between the cardiovascular and the respiratory system. They result from the respiratory-induced changes in intrathoracic pressure, which are transmitted to the cardiac cavities and to the changes in alveolar pressure, which may impact the lung microvessels. In spontaneously breathing patients, consequences of heart–lungs interactions are during inspiration an increase in right ventricular preload and afterload, a decrease in left ventricular preload and an increase in left ventricular afterload. In mechanically ventilated patients, consequences of heart–lungs interactions are during mechanical insufflation a decrease in right ventricular preload, an increase in right ventricular afterload, an increase in left ventricular preload and a decrease in left ventricular afterload. Physiologically and during normal breathing, heart–lungs interactions do not lead to significant hemodynamic consequences. Nevertheless, in some clinical settings such as acute exacerbation of chronic obstructive pulmonary disease, acute left heart failure or acute respiratory distress syndrome, heart–lungs interactions may lead to significant hemodynamic consequences. These are linked to complex pathophysiological mechanisms, including a marked inspiratory negativity of intrathoracic pressure, a marked inspiratory increase in transpulmonary pressure and an increase in intra-abdominal pressure. The most recent application of heart–lungs interactions is the prediction of fluid responsiveness in mechanically ventilated patients. The first test to be developed using heart–lungs interactions was the respiratory variation of pulse pressure. Subsequently, many other dynamic fluid responsiveness tests using heart–lungs interactions have been developed, such as the respiratory variations of pulse contour-based stroke volume or the respiratory variations of the inferior or superior vena cava diameters. All these tests share the same limitations, the most frequent being low tidal volume ventilation, persistent spontaneous breathing activity and cardiac arrhythmia. Nevertheless, when their main limitations are properly addressed, all these tests can help intensivists in the decision-making process regarding fluid administration and fluid removal in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasonography (LUS) is a non-invasive imaging method used to diagnose and monitor conditions such as pulmonary edema, pneumonia, and pneumothorax. It is precious where other imaging techniques like CT scan or chest X-rays are of limited access, especially in low- and middle-income countries with reduced resources. Furthermore, LUS reduces radiation exposure and its related blood cancer adverse events, which is particularly relevant in children and young subjects. The score obtained with LUS allows semi-quantification of regional loss of aeration, and it can provide a valuable and reliable assessment of the severity of most respiratory diseases. However, inter-observer reliability of the score has never been systematically assessed. This study aims to assess experienced LUS operators' agreement on a sample of video clips showing predefined findings. Methods: Twenty-five anonymized video clips comprehensively depicting the different values of LUS score were shown to renowned LUS experts blinded to patients' clinical data and the study's aims using an online form. Clips were acquired from five different ultrasound machines. Fleiss-Cohen weighted kappa was used to evaluate experts' agreement. Results: Over a period of 3 months, 20 experienced operators completed the assessment. Most worked in the ICU (10), ED (6), HDU (2), cardiology ward (1), or obstetric/gynecology department (1). The proportional LUS score mean was 15.3 (SD 1.6). Inter-rater agreement varied: 6 clips had full agreement, 3 had 19 out of 20 raters agreeing, and 3 had 18 agreeing, while the remaining 13 had 17 or fewer people agreeing on the assigned score. Scores 0 and score 3 were more reproducible than scores 1 and 2. Fleiss' Kappa for overall answers was 0.87 (95% CI 0.815–0.931, p < 0.001). Conclusions: The inter-rater agreement between experienced LUS operators is very high, although not perfect. The strong agreement and the small variance enable us to say that a 20% tolerance around a measured value of a LUS score is a reliable estimate of the patient's true LUS score, resulting in reduced variability in score interpretation and greater confidence in its clinical use. [ABSTRACT FROM AUTHOR]

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine quantitative ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate (p = 1e−4 for edema and p = 3e−7 for fibrosis) to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a clinical condition occurs due to severe systemic inflammatory response for clinical stimulus like pneumonia, sepsis, trauma, aspiration, inhalation of toxic gases, and pancreatitis. Disruption of alveolar barriers, activation of macrophages, infiltration of neutrophils, and proinflammatory cytokines are the vital events occurs during ALI. The drugs which inhibit these inflammatory response can protect lungs from inflammatory insults. In this study, we examined the potency of phytochemical coronarin, a diterpene which have been proven to possess anti-inflammatory, antioxidant, antiangiogenic, and antitumor activities. Healthy BALB/c mice were induced to acute lung injury with intra-tracheal administration of LPS and then treated with 5 and 10 mg/kg concentration of coronarin. The wet/dry lung weight of mice were estimated to assess the induction of pulmonary edema. BALF fluid was analyzed for protein concentrations and immune cells count. Myeloperoxidase activity and levels of chemokines MCP-2 and MIP-2, iNOS, COX-2, and PGE-2 were quantified to assess the immunomodulatory effect of coronarin against LPS-induced ALI. The levels of proinflammatory cytokines was measured to examine the anti-inflammatory property of coronarin, and it was confirmed with histopathological analysis of the lung tissue. Murine RAW 264.7 cells were utilized for the in vitro analysis. Cell cytoxicity and cytoprotective property of coronarin was assessed with MTT assay in LPS-treated Murine RAW 264.7. The anti-inflammatory property of coronarin was further confirmed in in vitro condition by estimating the levels of pro-inflammatory cytokines in coronarin-treated and untreated LPS-induced cells. Overall, our in vivo and in vitro results confirm coronarin significantly inhibited the infiltration of neutrophils prevented immunodulatory activity and synthesis of proinflammatory cytokines and alleviated the acute lung injury induced by LPS. Coronarin is a potent anti-inflammatory drug which can be subjected to further research to be prescribed as drug for ALI. [ABSTRACT FROM AUTHOR]

Purpose: To determine the safety and efficacy associated with drainage volumes greater than 1,500 mL in a single, unilateral thoracentesis without pleural manometry measurements. Materials and Methods: This retrospective, single-institution study included 872 patients (18 years and older) who underwent ultrasound-guided thoracentesis. Patient and procedures data were collected including demographics, number of and laterality of thoracenteses, volume and consistency of fluid removed, and whether clinical or radiologic evidence of re-expansion pulmonary edema (REPE) developed within 24 h of thoracentesis. Fisher's exact test was used to test the significance of the relationship between volume of fluid removed and evidence of REPE. Results: A total of 1376 thoracenteses were performed among the patients included in the study. The mean volume of fluid removed among all procedures was 901.1 mL (SD = 641.7 mL), with 194 (14.1%) procedures involving the removal of ≥ 1,500 mL of fluid. In total, six (0.7%) patients developed signs of REPE following thoracentesis, five of which were a first-time thoracentesis. No statistically significant difference in incidence of REPE was observed between those with ≥ 1,500 mL of fluid removed compared to those with < 1,500 mL of fluid removed (p-value = 0.599). Conclusions: Large-volume thoracentesis may safely improve patients' symptoms while preventing the need for repeat procedures. [ABSTRACT FROM AUTHOR]

The article discusses the anesthesia management of a 30-year-old pregnant patient with severe post-rheumatic mitral stenosis undergoing a cesarean section. The patient was stabilized pharmacologically and underwent a cesarean section under general anesthesia, followed by percutaneous mitral commissurotomy two weeks later. The patient's hemodynamic stability was maintained during the surgery, and she was discharged without complications after the procedure. The article emphasizes the importance of a multidisciplinary approach and careful planning for safe delivery in such challenging cases. [Extracted from the article]

Background: ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. Methods: The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. Conclusion: Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic progenitor cells are infused intravenously, known as hematopoietic stem cell transplantation. The range of pulmonary problems after transplantation of hematopoietic stem cells varies significantly from infectious to non-infectious aetiologies. Objectives: To study noninfectious respiratory complications in patients subjected to allogeneic bone marrow transplants. Patients and methods: This retrospective study was carried out on 1000 patients with hematopoietic stem-cell transplantations. These patients were presented with respiratory symptoms suggestive of pulmonary complications following bone marrow transplant. Result: The number of patients in this period was 1000 patients, and 247 of them had non-infectious pulmonary complications. Number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, graft-versus-host disease (GVHD), pulmonary edema, Bronchiolitis obliterans with GVHD, Chemotherapy pneumonitis, Idiopathic pneumonia syndrome and Thoracic air leak syndrome to all number of cases were twenty-five (2.5%), sixteen (1.6%), eighty-one (8.1) sixty-four (25.9%), nineteen (1.9%), twenty-one (2.1%), thirteen (1.3%) and eight (0.8%) respectively, but number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, GVHD, pulmonary edema, bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome to all complicated cases only were twenty-five (10.1%), sixteen (6.5%), eighty-one (32.8%), sixty-four (25.9 %), nineteen (7.7%), twenty-one (8.5 %), thirteen (5.3 %) and eight (3.2%) respectively. Conclusions: Noninfectious respiratory complications included GVHD, pulmonary edema, bronchiolitis obliterans and diffuse alveolar hemorrhage bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome. Some of them occurred early, and some occurred late. The incidence of non-infectious respiratory complications is affected by increased patient age and female gender. [ABSTRACT FROM AUTHOR]

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Background: Dengue is the most common arboviral illness reported globally, endemic to most tropical and sub-tropical regions of the world. Dengue Shock Syndrome is a rare complication of severe Dengue infection resulting in haemorrhagic complications and refractory hypotension. We report on a case of severe dengue diagnosed in a patient with major trauma and illustrate some of the potential challenges and considerations in the clinical management of such cases. Case Presentation: A 49-year-old female presented following a road trauma incident with multiple abdominal injuries requiring urgent laparotomy. Her recovery in Intensive Care Unit was complicated by the development of Dengue Shock Syndrome characterised by a falling haemoglobin and platelet count, multiorgan dysfunction and prolonged hospital stay. Conclusions: Dengue Shock Syndrome may complicate fluid management and bleeding control in major trauma cases. Awareness of Dengue, particularly in endemic areas and returned travellers may help facilitate early diagnosis and management of complications. [ABSTRACT FROM AUTHOR]

The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney–lung and lung–kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments. Here, the authors review the current understanding of interorgan crosstalk mechanisms, with a focus on interorgan communication in the kidney–lung axis during acute or chronic disease of the kidney or lung. Key points: Interorgan communication networks consist of soluble circulating factors, the immune system and the nervous system, and involve neuro-immune and neuro-endocrine interactions. Acute kidney injury (AKI) causes long-recognized complications, such as uraemia and volume overload, and less well understood "non-traditional" complications, such as remote organ dysfunction and immune dysfunction, which contribute to increased morbidity and mortality. AKI-induced remote lung inflammation depends on the actions of soluble circulating factors that are released by the kidney and other organs, including osteopontin, HMGB1, IL-6, IL-8 and TNF, and of immune cells, including neutrophils, monocytes, macrophages and T cells. Primary lung injury due to infection, acid aspiration, ischaemia–reperfusion injury or barotrauma can lead to AKI in rodents and humans; some of the mechanisms of lung–kidney crosstalk are similar to those implicated in kidney–lung crosstalk, but more mechanistic studies are required. Studies in preclinical models and correlative evidence from clinical studies suggest a bidirectional detrimental relationship between chronic kidney disease and chronic lung disease; however, the molecular mechanisms are largely unknown. [ABSTRACT FROM AUTHOR]

Purpose: Neurogenic pulmonary edema (NPE) combined with Takotsubo cardiomyopathy (TCM) is a rare condition associated with aneurysmal subarachnoid hemorrhage (aSAH). Although several mechanisms have been proposed, the pathophysiology and management strategies are not yet fully established. We aimed to determine the radiological and clinical outcomes of patients with NPE and with TCM after aSAH to propose management strategies. Methods: We analyzed the data of 564 patients with aSAH recorded at a single medical center from February 2015 to July 2022. This study retrospectively investigated the incidence and demographics of SAH combined with both NPE and TCM and the clinical outcomes of the patients. Correlating factors, independently associated with NPE-TCM, were also investigated. Results: During the 7 years, 11 (2.0%) of 564 patients had NPE complicated with TCM after aSAH. Seven of 11 (63.6%) patients had poor-grade SAH (Hunt–Hess Grade 4 to 5). Three of 11 patients had a posterior circulation in the NPE-TCM group. The most prevalent treatment option was endovascular coil embolization, except for one case of clip. Long-term outcomes were favorable in 6 of 11 patients, and there was one case of mortality. Age, troponin I level, and alveolar-arterial oxygen gradient were correlating factors of NPE-TCM. Conclusion: Although NPE-TCM represents a rare complication associated with aSAH, achieving active resolution of underlying neurological causes through early and appropriate treatment may contribute to a favorable prognosis. Considering the limited incidence of SAH complicated with NPE-TCM, a multi-center study may be needed. [ABSTRACT FROM AUTHOR]

Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO2/FiO2 ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO2/FiO2 ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype. [ABSTRACT FROM AUTHOR]

Background: Immersion Pulmonary Edema (IPE) is a common and potentially serious diving accident that can have significant respiratory and cardiac consequences and, in some cases, be fatal. Our objective was to characterize cases of IPE among military trainees and recreational divers and to associate their occurrence with exposure and individual background factors such as age and comorbidity. We conducted a retrospective analysis on the medical records and diving parameters of all patients who were treated for IPE at the Hyperbaric Medicine Department of Sainte-Anne Military Hospital in Toulon, France, between January 2017 and August 2019. In total, 57 subjects were included in this study, with ages ranging from 20 to 62 years. These subjects were divided into two distinct groups based on exposure categories: (1) underwater/surface military training and (2) recreational scuba diving. The first group consisted of 14 individuals (25%) with a mean age of 26.5 ± 2.6 years; while, the second group comprised 43 individuals (75%) with a mean age of 51.2 ± 7.5 years. All divers under the age of 40 were military divers. Results: In 40% of cases, IPE occurred following intense physical exercise. However, this association was observed in only 26% of recreational divers, compared to 86% of military divers. Among civilian recreational divers, no cases of IPE were observed in subjects under the age of 40. The intensity of symptoms was similar between the two groups, but the duration of hospitalization was significantly longer for the recreational subjects. Conclusion: It seems that the occurrence of IPE in young and healthy individuals requires their engagement in vigorous physical activity. Additionally, exposure to significant ventilatory constraints is a contributing factor, with the intensity of these conditions seemingly exclusive to military diving environments. In contrast, among civilian recreational divers, IPE tends to occur in subjects with an average age twice that of military divers. Moreover, these individuals exhibit more prominent comorbidity factors, and the average level of environmental stressors is comparatively lower. Key points: In the case of young, well-trained military divers without cardiovascular pathology, we have observed that the occurrence of IPE requires the simultaneous presence of intense finning exercise and/or a high negative Static Lung Load (SSL) during immersion. However, among civilian recreational divers, no instances of IPE were observed in individuals under the age of 40. In civilian divers, IPE appears to be more common among those who are older than their military counterparts (Average age/medians: 51.2 ± 7.5 years) and may possess cardiovascular risk factors. Even milder environmental constraints (associated with a low negative SLL) seem sufficient to induce IPE in this particular group of divers. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effect of freediving depth on risk for hypoxic blackout by recording arterial oxygen saturation (SpO2) and heart rate (HR) during deep and shallow dives in the sea. Methods: Fourteen competitive freedivers conducted open-water training dives wearing a water-/pressure proof pulse oximeter continuously recording HR and SpO2. Dives were divided into deep (> 35 m) and shallow (10–25 m) post-hoc and data from one deep and one shallow dive from 10 divers were compared. Results: Mean ± SD depth was 53 ± 14 m for deep and 17 ± 4 m for shallow dives. Respective dive durations (120 ± 18 s and 116 ± 43 s) did not differ. Deep dives resulted in lower minimum SpO2 (58 ± 17%) compared with shallow dives (74 ± 17%; P = 0.029). Overall diving HR was 7 bpm higher in deep dives (P = 0.002) although minimum HR was similar in both types of dives (39 bpm). Three divers desaturated early at depth, of which two exhibited severe hypoxia (SpO2 ≤ 65%) upon resurfacing. Additionally, four divers developed severe hypoxia after dives. Conclusions: Despite similar dive durations, oxygen desaturation was greater during deep dives, confirming increased risk of hypoxic blackout with increased depth. In addition to the rapid drop in alveolar pressure and oxygen uptake during ascent, several other risk factors associated with deep freediving were identified, including higher swimming effort and oxygen consumption, a compromised diving response, an autonomic conflict possibly causing arrhythmias, and compromised oxygen uptake at depth by lung compression possibly leading to atelectasis or pulmonary edema in some individuals. Individuals with elevated risk could likely be identified using wearable technology. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: We report a case in which veno-venous extracorporeal membrane oxygenation (V-V ECMO) saved the life of a patient who developed severe hypoxemia due to unusual unilateral pulmonary edema (UPE) after cardiopulmonary bypass (CPB). Case presentation: A 69-year-old man underwent aortic valve replacement and coronary artery bypass grafting. Following uneventful weaning off CPB, he developed severe hypoxemia. The ratio of arterial oxygen tension to inspired oxygen fraction (PaO2/FiO2) decreased from 301 mmHg 5 min after CPB to 42 mmHg 90 min after CPB. A chest X-ray revealed right-sided UPE. Immediately established V-V ECMO increased PaO2/FiO2 to 170 mmHg. Re-expansion pulmonary edema (REPE) was likely, as the right lung remained collapsed during CPB following the accidental opening of the right chest cavity during graft harvesting. Conclusions: V-V ECMO was effective in improving oxygenation and saving the life of a patient who had fallen into unilateral REPE unusually developing after conventional CPB. [ABSTRACT FROM AUTHOR]

Background: Acute post-streptococcal glomerulonephritis (APSGN) is common in developing countries with a high hospitalization rate. Most patients have acute nephritic syndrome features, although some occasionally present with unusual clinical features. This study aims to describe and analyze clinical features, complications, and laboratory parameters in children diagnosed with APSGN at presentation, 4 and 12 weeks later, in a resource-limited setting. Methods: This cross-sectional study was conducted among children < 16 years with APSGN between January 2015 and July 2022. Hospital medical records and outpatient cards were reviewed for clinical findings, laboratory parameters, and kidney biopsy results. Descriptive analysis of multiple categorical variables was performed using SPSS version 16.0 and presented as frequencies and percentages. Results: The study included 77 patients. Most (94.8%) were older than five years, and age group 5–12 years had highest prevalence (72.7%). Boys were affected more frequently than girls (66.2% vs. 33.8%). Edema (93.5%), hypertension (87%), and gross hematuria (67.5%) were the most frequent presenting symptoms, and pulmonary edema (23.4%) was the most common severe complication. Anti-DNase B and anti-streptolysin O titers were positive in 86.9% and 72.7%, respectively, and 96.1% had C3 hypocomplementemia. Most clinical features resolved in three months. However, at 3 months, 6.5% of patients had persistent hypertension, impaired kidney function, and proteinuria alone or in combination. Most patients (84.4%) had an uncomplicated course; 12 underwent kidney biopsy, 9 required corticosteroids, and 1 required kidney replacement therapy. There was no mortality during the study period. Conclusion: Generalized swelling, hypertension, and hematuria were most common presenting features. Persistent hypertension, impaired kidney function, and proteinuria persisted in a small proportion who had a significant clinical course and required kidney biopsy. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS. Objectives: This study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS. Methods: In this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS–ARDS), an 8-region anterior–lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated. Results: 26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS (r = 0.54), LUS–ARDS (r = 0.58) and anterior–lateral score (r = 0.54) correlated significantly with EVLWi, while the B-line score did not (r = 0.32). ∆global LUS (r = 0.49) and ∆anterior–lateral LUS (r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior–lateral and 0.85 for the LUS–ARDS score. Conclusions: Overall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate–to–severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering pleural morphology may be of added value. Trial registration: ClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020–005447-23. [ABSTRACT FROM AUTHOR]

Negative-pressure pulmonary edema (NPPE) is a rare respiratory complication due to acute upper airway obstruction occurring shortly after extubation. We report a case of NPPE in young adult patient who underwent an eventful general anesthesia. The patient presented laryngospasm followed by acute respiratory distress with pink frothy sputum. The NPPE was initially misdiagnosed, and a preventable tracheostomy was performed. NPPE was managed with mechanical ventilation and diuretics, and the patient had full recovery. Every anesthesiologist should be aware of the diagnosis of NPPE. Early recognition and management are essential to prevent the morbidity associated with NPPE in young healthy patients. [ABSTRACT FROM AUTHOR]

Drowning is the leading cause of death by accident of everyday life in people under 25 years of age. Xenobiotics are frequently involved in drowning cases but their influence on the diagnosis of fatal drowning has not been studied so far. This preliminary study aimed to assess the influence of an alcohol and/or a drug intoxication on the autopsy signs of drowning, and on the results of diatom analyses in drowning deaths. Twenty-eight autopsy cases of drowning including 19 freshwater drownings, 6 seawater drownings, and 3 brackish water drownings were prospectively included. Toxicological and diatom tests were performed in each case. The influence of alcohol and other xenobiotics on drowning signs and diatom analyses was assessed separately then in combination through a global toxicological participation score (GTPS). Diatom analyses showed positive results in lung tissue in every case. No significant association was found between the degree of intoxication and the diatom concentration in the organs, even after considering freshwater drowning cases only. The vast majority of the traditional autopsy signs of drowning were not significantly affected by the individual toxicological status either, with the exception of lung weight which tended to raise in case of intoxication, probably due to the pulmonary edema and congestion increase. Further research on larger autopsy samples is needed to confirm the results of this exploratory study. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0–6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage is a medical emergency that necessitates direct transfer to a tertiary referral center specialized in the diagnosis and treatment of this condition. The initial hours after aneurysmal rupture are critical for patients with aneurysmal subarachnoid hemorrhage, both in terms of rebleeding and combating the effect of early brain injury. No good treatment options are available to reduce the risk of rebleeding before aneurysm occlusion. Lowering the blood pressure may reduce the risk of rebleeding but carries a risk of inducing delayed cerebral ischemia or aggravating the consequences of early brain injury. Early brain injury after aneurysmal rupture has an important effect on final clinical outcome. Proper cerebral perfusion is pivotal in these initial hours after aneurysmal rupture but threatened by complications such as neurogenic pulmonary edema and cardiac stunning, or by acute hydrocephalus, which may necessitate early drainage of cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

We studied the effect of a new indolinone derivative GRS on animal survival and on functioning and histological structure of the lungs in rats with experimental pneumonitis. The rats of experimental groups were intratracheally administered 0.5% aqueous solution of carrageenan under intramuscular anesthesia. Compound GRS (10 mg/kg; a suspension in 0.5% aqueous solution of carboxymethyl cellulose) was orally administered for 4 days starting from the day of carrageenan administration; another rat group received the aqueous solution of carboxymethyl cellulose alone. Control rats received intratracheally isotonic solution of sodium chloride. Animal mortality was registered over 5 days; on day 5, the respiratory parameters were measured, the lungs were weighed, pulmonary edema was evaluated, and histological structure of the lungs was studied. GRS compound improved survival of animals with modeled pneumonitis, restored the respiratory parameters to the level of control animals, and reduced pulmonary edema by 35% and the severity of histological damage score in the lungs by 17% (p<0.05). [ABSTRACT FROM AUTHOR]

Neurogenic pulmonary edema (NPE) is a life-threatening and severe complication in patients with spontaneous subarachnoid hemorrhage (SAH). The prevalence of NPE varies significantly across studies due to differences in case definitions, study populations, and methodologies. Therefore, a precise estimation of the prevalence and risk factors related to NPE in patients with spontaneous SAH is important for clinical decision-makers, policy providers, and researchers. We conducted a systematic search of the PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane Library databases from their inception to January 2023. Thirteen studies were included in the meta-analysis, with a total of 3,429 SAH patients. The pooled global prevalence of NPE was estimated to be 13%. Out of the eight studies (n = 1095, 56%) that reported the number of in-hospital mortalities of NPE among patients with SAH, the pooled proportion of in-hospital deaths was 47%. Risk factors associated with NPE after spontaneous SAH included female gender, WFNS class, APACHE II score ≥ 20, IL-6 > 40 pg/mL, Hunt and Hess grade ≥ 3, elevated troponin I, elevated white blood cell count, and electrocardiographic abnormalities. Multiple studies showed a strong positive correlation between the WFNS class and NPE. In conclusion, NPE has a moderate prevalence but a high in-hospital mortality rate in patients with SAH. We identified multiple risk factors that can help identify high-risk groups of NPE in individuals with SAH. Early prediction of the onset of NPE is crucial for timely prevention and early intervention. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO), an inorganic arsenical, is a toxic environmental contaminant. It is also a widely used chemical with industrial and medicinal uses. Significant public health risk exists from its intentional or accidental exposure. The pulmonary pathology of acute high dose exposure is not well defined. We developed and characterized a murine model of a single inhaled exposure to ATO, which was evaluated 24 h post-exposure. ATO caused hypoxemia as demonstrated by arterial blood-gas measurements. ATO administration caused disruption of alveolar-capillary membrane as shown by increase in total protein and IgM in the bronchoalveolar lavage fluid (BALF) supernatant and an onset of pulmonary edema. BALF of ATO-exposed mice had increased HMGB1, a damage-associated molecular pattern (DAMP) molecule, and differential cell counts revealed increased neutrophils. BALF supernatant also showed an increase in protein levels of eotaxin/CCL-11 and MCP-3/CCL-7 and a reduction in IL-10, IL-19, IFN-γ, and IL-2. In the lung of ATO-exposed mice, increased protein levels of G-CSF, CXCL-5, and CCL-11 were noted. Increased mRNA levels of TNF-a, and CCL2 in ATO-challenged lungs further supported an inflammatory pathogenesis. Neutrophils were increased in the blood of ATO-exposed animals. Pulmonary function was also evaluated using flexiVent. Consistent with an acute lung injury phenotype, respiratory and lung elastance showed significant increase in ATO-exposed mice. PV loops showed a downward shift and a decrease in inspiratory capacity in the ATO mice. Flow-volume curves showed a decrease in FEV0.1 and FEF50. These results demonstrate that inhaled ATO leads to pulmonary damage and characteristic dysfunctions resembling ARDS in humans. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a global public health burden, characterized by frequent emergency department (ED) visits and hospitalizations. Identifying successful strategies to avoid admissions is crucial for the management of acutely decompensated HF, let alone resource utilization. The primary challenge for ED management of patients with acute heart failure (AHF) lies in the identification of those who can be safely discharged home instead of being admitted. This is an elaborate decision, based on limited objective evidence. Thus far, current biomarkers and risk stratification tools have had little impact on ED disposition decision-making. A reliable definition of a low-risk patient profile is warranted in order to accurately identify patients who could be appropriate for early discharge. A brief period of observation can facilitate risk stratification and allow for close monitoring, aggressive treatment, continuous assessment of response to initial therapy and patient education. Lung ultrasound may represent a valid bedside tool to monitor cardiogenic pulmonary oedema and determine the extent of achieved cardiac unloading after treatment in the observation unit setting. Safe discharge mandates multidisciplinary collaboration and thoughtful assessment of socioeconomic and behavioural factors, along with a clear post-discharge plan put forward and a close follow-up in an outpatient setting. Ongoing research to improve ED risk stratification and disposition of AHF patients may mitigate the tremendous public health challenge imposed by the HF epidemic. [ABSTRACT FROM AUTHOR]

Background: Immersion pulmonary edema (IPE) is a frequent diving accident, and it is the primary cause of hospitalization for young military divers during training. The objective of this study was to identify immersion-induced parameters predicting individual susceptibility to IPE. Methods: Eighteen experienced male divers having completed at least 100 dives were recruited. Eight divers had previously been hospitalized for IPE (IPE), and the other ten had never developed IPE (non-IPE). The two groups were matched for age, BMI, and number of dives performed. Ventilatory function and overall compliance of the respiratory system (Crs) were measured on land and during head-out-of-water immersion. Subjects also performed 30 min of fin swimming in a channel at 33 m min−1. Following this exercise, the presence of extravascular lung water, revealed by ultrasound lung comets (ULC), was assessed. Results: In the whole group, the decrease in Crs upon immersion correlated with the immersion-induced alterations to expiratory reserve volume, ERV (r2 = 0.91; p < 0.001), inspiratory reserve volume, IRV (r2 = 0.94; p < 0.001), and tidal volume, Vt, changes (r2 = 0.43; p < 0.003). The number of ULC correlated strongly with immersion-induced changes in ventilatory function (r2 = 0.818; p < 0.001 for ERV, r2 = 0.849; p < 0.001 for IRV, r2 = 0.304; p = 0.0164 for Vt) and reduced Crs (r2 = 0.19; p < 0.001). The variations of ERV, IRV, and Crs at rest induced by head-out-of-water immersion and the number of ULC measured after swimming for 30 min were significantly greater in IPE subjects. Conclusion: In the face of similar immersion stresses, the extent of alterations to ventilatory function and the number of ULCs were very different between individuals but remained statistically correlated. These parameters were significantly greater in divers with a history of IPE. Alterations to pulmonary function and, in particular, to pulmonary compliance induced by head-out-of-water immersion, through their effects on work of breathing appear to allow the identification of divers with a greater susceptibility to developing IPE. Measurement of these parameters could therefore be proposed as a predictive test for the risk of developing IPE. Key Points: Immersion Pulmonary Edema (IPE) can occur in highly fit individuals, such as military divers and triathletes, and is the leading cause of hospitalization among young military divers during training. To preserve the health of young divers, predictive tests of individual susceptibility to IPE should be proposed, similar to those proposed for High Altitude Pulmonary Edema (HAPE). Our findings confirm the fundamental role of immersion-induced changes in lung function in the development of IPE. Alterations in pulmonary function, particularly pulmonary compliance, appear to allow for identification of divers with a higher susceptibility to developing IPE. [ABSTRACT FROM AUTHOR]

Copyright of Die Kardiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We investigated the agreement between remote dielectric sensing (ReDS) system, which is a recently introduced non-invasive technology to quantify the degree of pulmonary congestion, and lung ultrasound (LUS), which is a gold standard to assess the existence of severe pulmonary congestion. Consecutive patients who were hospitalized to examine the cause of heart failure and treat their heart failure in our institute were prospectively included. They received LUS and simultaneous ReDS measurements. Three or more B-lines at each LUS zone was assigned to B-profile positive, indicating the existence of significant pulmonary congestion. ReDS values ≥ 35% were defined as significant pulmonary congestion. A total of 19 heart failure patients were included (77 years, 13 men). Plasma B-type natriuretic peptide level was 131 (36, 416) pg/ml. Three patients had B-profile, indicating significant pulmonary congestion, and two of them had ≥ 35% of ReDS (sensitivity 66.7%, specificity 87.5%, and negative predictive value 93.3%). Most of the patients (79%) had lower B-lines below 3 and did not satisfy the criteria of B-profile, irrespective of wide ranges of ReDS values. ReDS system had as acceptable predictability as LUS in assessing the existence of significant pulmonary congestion. ReDS would be recommended to rule out significant pulmonary congestion or quantify the degree of less significant pulmonary congestion. [ABSTRACT FROM AUTHOR]

Background: Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. Methods: Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. Results: Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. Conclusions: This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adults for refractory cardiogenic shock has risen exponentially during the prior decade. Although VA-ECMO provides cardiopulmonary support, it can alter left ventricular (LV) loading conditions leading to LV distension, which makes the lungs susceptible to congestion and promotes intracardiac thrombosis. These conditions can be alleviated by pharmacologic and mechanical unloading, but gaps in knowledge remain on optimal timing and methods of this approach. This review provides an overview of the epidemiology of VA-ECMO, describes pathophysiology and methods for monitoring and reducing LV loading and summarizes contemporary studies examining the association between LV unloading and adverse events. We offer a simple protocol for implementing LV unloading during VA-ECMO to provide pulmonary protection and improve outcomes. [ABSTRACT FROM AUTHOR]

The clinical use of lung ultrasound (LUS) has made more efficient many diagnostic processes at bedside. The great power of LUS is a superior diagnostic sensitivity in many applications, when compared to chest radiography (CXR). The implementation of LUS in emergency is contributing to reveal a growing number of radio-occult pulmonary conditions. In some diseases, the superior sensitivity of LUS is a great advantage, like for pneumothorax and pulmonary edema. Diagnosing at bedside pneumothoraxes, pulmonary congestions, and COVID-19 pneumonia that are visible by LUS but undetected by CXR may be decisive for appropriate management, and even for saving lives. However, in other conditions, like bacterial pneumonia and small peripheral infarctions due to subsegmental pulmonary embolism, the high sensitivity of LUS does not always lead to advantages. Indeed, we doubt that it is always necessary to treat by antibiotics patients suspected of lower respiratory tract infection, who show radio-occult pulmonary consolidations, and to treat by anticoagulation patients with small subsegmental pulmonary embolism. The possibility that we are overtreating radio-occult conditions should be investigated with dedicated clinical trials. [ABSTRACT FROM AUTHOR]

Deaths at high altitudes may arise from a range of quite disparate entities including trauma (e.g. falls), environmental factors (e.g. hypothermia and hypoxia), and pre-existing medical conditions (e.g. coronary artery disease). Unique conditions include high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) which may contribute to lethal mechanisms or precipitate a traumatic event. Forensic issues that may arise in these cases are logistical problems due to remote locations, sometimes with failure to find a body, delay in discovery and/or repatriation, prior local autopsies being performed with embalming, and the non-specificity of pathology markers. Traumatic deaths involve blunt force impacts, falls, suffocation, crush asphyxia and hypothermia. The assessment of cases requires careful integration of the autopsy findings with the medical history of the decedent and an accurate description of their behaviour in the hours leading up to death. [ABSTRACT FROM AUTHOR]

Introduction: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar–capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions.Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar–capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions.The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E′, which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (− 26 ± 13 versus − 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction.After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar–capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise.Methods: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar–capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions.Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar–capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions.The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E′, which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (− 26 ± 13 versus − 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction.After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar–capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise.Results: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar–capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions.Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar–capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions.The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E′, which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (− 26 ± 13 versus − 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction.After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar–capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise.Conclusion: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar–capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions.Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar–capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions.The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E′, which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (− 26 ± 13 versus − 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction.After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar–capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EV-A71) is one of the major pathogens responsible for hand, foot, and mouth disease (HFMD). Many HFMD outbreaks have been reported throughout the world in the past decades. Compared with other viruses, EV-A71 infection is more frequently associated with severe neurological complications and even death in children. EV-A71 can also infect adults and cause severe complications and death, although such cases are very uncommon. Although fatal cases of EV-A71 infection have been reported, the underlying mechanisms of EV-A71 infection, especially the mode of viral spread into the central nervous system (CNS) and mechanisms of pulmonary edema, which is considered to be the direct cause of death, have not yet been fully clarified, and more studies are needed. Here, we first summarize the pathological findings in various systems of patients with fatal EV-A71 infections, focussing in detail on gross changes, histopathological examination, tissue distribution of viral antigens and nucleic acids, systemic inflammatory cell infiltration, and tissue distribution of viral receptors and their co-localization with viral antigens. We then present our conclusions about viral dissemination, neuropathogenesis, and the mechanism of pulmonary edema in EV-A71 infection, based on pathological findings. [ABSTRACT FROM AUTHOR]

Ascent to high altitude (> 3000 m height above sea level or m.a.s.l) exposes people to hypobaric atmospheric pressure and hypoxemia, which provokes mountain sickness and whose symptoms vary from the mild acute mountain sickness to the life-threatening, high-altitude pulmonary edema (HAPE). This study analysed the risk factors underlying HAPE in dwellers and travellers of the Ecuadorian Andes after sojourning over 3000 m height. A group of HAPE patients (N = 58) was compared to a NO HAPE group (N = 713), through demographic (ethnicity, sex, and age), red blood cell parameters (erythrocytes counts, hematocrit, median corpuscular volume, median corpuscular haemoglobin, and median corpuscular haemoglobin concentration (MCHC)), altitude (threshold: 3000 m.a.s.l.), and health status (vital signs) variables. Analysis of Deviance for Generalised Linear Model Fits (logit regression) revealed patterns of significant associations. High-altitude dwellers, particularly children and elder people, were HAPE-prone, while women were more tolerant of HAPE than men. Interestingly, HAPE prevalence was strongly related to an increment of MCH. The residence at middle altitude was inversely related to the odds of suffering HAPE. Ethnicity did not have a significant influence in HAPE susceptibility. Elevated MCHC emerges like a blood adaptation of Andean highlanders to high altitude and biomarker of HAPE risk. [ABSTRACT FROM AUTHOR]

Acute Lung Injury (ALI) due to inhaled pathogens causes high mortality. Underlying mechanisms are inadequately understood. Here, by optical imaging of live mouse lungs we show that a key mechanism is the viability of cytosolic Ca2+ buffering by the mitochondrial Ca2+ uniporter (MCU) in the lung's surfactant-secreting, alveolar type 2 cells (AT2). The buffering increased mitochondrial Ca2+ and induced surfactant secretion in wild-type mice, but not in mice with AT2-specific MCU knockout. In the knockout mice, ALI due to intranasal LPS instillation caused severe pulmonary edema and mortality, which were mitigated by surfactant replenishment prior to LPS instillation, indicating surfactant's protective effect against alveolar edema. In wild-type mice, intranasal LPS, or Pseudomonas aeruginosa decreased AT2 MCU. Loss of MCU abrogated buffering. The resulting mortality was reduced by spontaneous recovery of MCU expression, or by MCU replenishment. Enhancement of AT2 mitochondrial buffering, hence endogenous surfactant secretion, through MCU replenishment might be a therapy against ALI. Acute lung injury caused by inhalation of pathogens leads to mortality, but the mechanisms are unclear. Here, the authors show in mice that that loss of the mitochondrial calcium uniporter (MCU) of alveolar type 2 cells (AT2) impaired mitochondrial Ca2+ buffering and surfactant secretion, and increased mortality, in response to LPS instillation, suggesting the MCU as a potential therapeutic target in ALI. [ABSTRACT FROM AUTHOR]

Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24 h to normoxia or hypoxia (10% N2 in O2). They were infused with either 0.9% NaCl solution (normoxic/hypoxic controls) or relaxin at two doses (15 and 75 μg kg−1 day−1). After 24 h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35–40% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation. [ABSTRACT FROM AUTHOR]

We studied the content of aquaporin-5 (AQP5) and epithelial sodium channel (ENaC) in rat lungs during the development of toxic pulmonary edema (TPE) caused by intoxication with phosgene and perfluoroisobutylene (1.5 LC50). The lung body weight index (LBI) was calculated and histological examination of the lung tissues was performed. Localization and expression of AQP5 and ENaC were determined by immunohistochemistry. Intoxication led to a significant (p<0.05) increase in LBI and histological changes typical of TPE 1 and 3 h after the exposure. In 1 and 3 h after phosgene intoxication, the AQP5 and ENaC content significantly (p<0.05) increased in comparison with the control. Similar changes in the AQP5 and ENaC content were observed 1 and 3 h after exposure to perfluoroisobutylene. It was hypothesized that AQP5 plays an important role in the formation of TPE caused by intoxication with acylating pulmonotoxicants. An increase in the content of ENaC can be considered as a compensatory reaction of the body aimed at clearance of the alveolar fluid. [ABSTRACT FROM AUTHOR]

Previous studies have reported contradictory findings on the utility of remote physiological monitoring (RPM)-guided management of patients with chronic heart failure (HF). Multiple databases were searched for studies that evaluated the clinical efficacy of RPM-guided management versus standard of care (SOC) for HF patients. The primary outcome was HF-related hospitalization (HFH). The secondary outcomes were all-cause mortality, cardiovascular-related (CV) mortality, and emergency department (ED) visits. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using a random-effects model. A total of 16 randomized controlled trials, including 8679 HF patients (4574 managed with RPM-guided therapy vs. 4105 managed with SOC), were included in the final analysis. The average follow-up period was 15.2 months. There was no significant difference in HFH rate between the two groups (RR: 0.94; 95% CI: 0.84–1.07; P = 0.36). Similarly, there were no significant differences in CV mortality (RR 0.86, 95% CI 0.73–1.02, P = 0.08) or in ED visits (RR 0.80, 95% CI 0.59–1.08, P = 0.14). However, RPM-guided therapy was associated with a borderline statistically significant reduction in all-cause mortality (RR: 0.88; 95% CI: 0.78–1.00; P = 0.05). Subgroup analysis based on the strategy of RPM showed that both hemodynamic and arrhythmia telemonitoring–guided management can reduce the risk of HFH (RR: 0.79; 95% CI: 0.64–0.97; P = 0.02) and (RR: 0.79; 95% CI: 0.67–0.94; P = 0.008) respectively. Our study demonstrated that RPM-guided diuretic therapy of HF patients did not reduce the risk of HFH but can improve survival. Hemodynamic and arrhythmia telemonitoring–guided management could reduce the risk of HF-related hospitalizations. [ABSTRACT FROM AUTHOR]

Purpose: Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated AHF (ADHF) is then presented. Methods: Myocardial infarction (MI) was induced by occlusion of left anterior descending coronary artery in 17 male pigs (34 ± 4 kg). Two weeks later, ADHF was induced in the survived animals (n = 15) by occlusion of the circumflex coronary artery, associated with acute volume overload and increases in arterial blood pressure by vasoconstrictor infusion. After onset of ADHF, animals received 48-h iv infusion of either serelaxin (n = 9) or placebo (n = 6). The pathophysiology and progression of ADHF were described by combining evaluation of hemodynamics, echocardiography, bioimpedance, blood gasses, circulating biomarkers, and histology. Results: During ADHF, animals showed reduced left ventricle (LV) ejection fraction < 30%, increased thoracic fluid content > 35%, pulmonary edema, and high pulmonary capillary wedge pressure ~ 30 mmHg (p < 0.01 vs. baseline). Other ADHF-induced alterations in hemodynamics, i.e., increased central venous and pulmonary arterial pressures; respiratory gas exchanges, i.e., respiratory acidosis with low arterial PO2 and high PCO2; and LV dysfunction, i.e., increased LV end-diastolic/systolic volumes, were observed (p < 0.01 vs. baseline). Representative increases in circulating cardiac biomarkers, i.e., troponin T, natriuretic peptide, and bio-adrenomedullin, occurred (p < 0.01 vs. baseline). Finally, elevated renal and liver biomarkers were observed 48 h after onset of ADHF. Mortality was ~ 50%. Serelaxin showed beneficial effects on congestion, but none on mortality. Conclusion: This new model, resulting from a combination of chronic and acute MI, and volume and pressure overload, was able to reproduce all the typical clinical signs occurring during ADHF in a consistent and reproducible manner. [ABSTRACT FROM AUTHOR]