Pulmonary Edema Research Articles

Neurogenic pulmonary edema: a case report and literature review

Neurogenic pulmonary edema: a case report and literature review

Dexamethasone alleviates acute lung injury in a rat model with venovenous extracorporeal membrane oxygenation support

BackgroundIn recent years, dexamethasone (Dex) has been used to treat acute respiratory distress syndrome (ARDS) in patients with COVID-19 and achieved promising outcomes. Venovenous extracorporeal membrane oxygenation (VV ECMO) support...

Neutral Polysaccharide from Platycodonis Radix-Ameliorated PM2.5-Induced Lung Injury by Inhibiting the TLR4/NF-κB p65 Pathway and Regulating the Lung and Gut Microbiome.

Platycodonis radix (PR) has been reported to play a protective role in lung injury. However, much less is known about the protective effect and mechanism of its main component PR polysaccharides (PRPs) in particulate matter (PM2.5)-induced lung injury. Here, a neutral polysaccharide (MW: 244.56 kDa) was isolated from PR, mainly composed of Rha, Ara, Gal, Glc, Xyl, and Man. PRPs significantly improved PM2.5-induced pulmonary edema, oxidative damage, and cell apoptosis and downregulated inflammatory factor levels in bronchoalveolar lavage fluid. Mechanistically, PRPs reduced intestinal mucosal barrier damage, thereby lowering serum lipopolysaccharide levels and inhibiting the overactivation of the TLR4/NF-κB signaling pathway in the lung tissue. Notably, PRPs could optimize the composition of pulmonary and intestinal microbiota. Oral administration of PRPs resulted in enrichment of short-chain fatty acid (SCFA)-producing bacteria, thereby upregulating the levels of acetate, butyrate, and isovalerate. Taken together, PRPs have great potential in preventing and repairing the lung injury caused by PM2.5.

Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis

BackgroundSepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis.ResultsSepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival.ConclusionsTreatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis.

Deep learning model for detection acute cardiogenic pulmonary edema in cases of preeclampsia

<span lang="EN-US">The physiological changes during the pregnancy period increase the risk of developing pulmonary edema and acute respiratory failure. This condition falls under critical medical emergencies associated with maternal mortality. This study utilized a convolutional neural networks (CNN) architectural model employing chest Xray dataset images. CNN utilizes the convolution process by moving a convolutional kernel of a certain size across an image, allowing the computer to derive new representative information from the multiplication of portions of the image with the utilized filter.</span><span lang="EN-US">To simplify, the vanishing gradient issue occurs when information dissipates before reaching its destination due to the lengthy path between input and output layers. This study was developed model for detection acute cardiogenic pulmonary Edema in pre-eclampsia cases using chest Xray images, implemented using PyTorch, Keras, and MxNet. The validated model achieved its optimum with accuracy 90.65% and binary cross-entropy loss (BCELoss) value of 0.4538. It exhibited an improved sensitivity value of 83.514% using a 5% dataset and a specificity value of 57.273%. This indicates an increase in sensitivity value by 83.514% using a 5% data set and a specificity value of 57.273%. The research results demonstrate an improvement in accuracy compared to several similar studies that also utilized CNN models.</span>

Swimming-Induced Pulmonary Edema in a Member Participating in a Special Tactics Selection Course

Swimming-Induced Pulmonary Edema in a Member Participating in a Special Tactics Selection Course

Lung parenchymal and pleural findings on computed tomography after out-of-hospital cardiac arrest

IntroductionLung injury and the acute respiratory distress syndrome (ARDS) are common after out-of-hospital cardiac arrest (OHCA), but the imaging characteristics of lung parenchymal and pleural abnormalities in these patients have not been well-characterized. We aimed to describe the incidence of lung parenchymal and pleural findings among patients who had return of spontaneous circulation (ROSC) and who underwent computed tomography (CT) of the chest after OHCA. MethodsThis was a retrospective cohort study conducted at two academic hospitals from 2014 to 2019. We included adults successfully resuscitated from OHCA who received a head-to-pelvis or dedicated chest CT scan. The composite primary outcome was the incidence of lung parenchymal and pleural abnormalities. CT scans were overread by attending radiologists and lung parenchymal and pleural findings were categorized based on predefined criteria. Data are presented as absolute numbers and percentages. We examined the associations between CPR duration, time to successful intubation, and outcome using multivariable analyses. ResultsWe evaluated 204 eligible patients. Mean age was 54 years and 33 % were women. An initial shockable rhythm was found in 27 % and in 72 patients (36 %) the presumed etiology of OHCA was cardiac. A total of 133 patients underwent head-to-pelvis CT and 71 patients had dedicated chest CT. The median time from 911 call to CT scan was 2.5 (IQR 2.0–3.4) hours. A total of 160 (78 %) of patients had abnormal lung parenchyma or pleural findings. Patients with longer CPR duration or longer time to successful intubation had a higher incidence of abnormal lung findings on CT. ConclusionOver three-quarters of patients who survived to the hospital post OHCA and received a chest CT had lung parenchymal or pleural abnormalities, the most common of which were aspiration, pulmonary edema, and consolidation/pneumonia. Future planned research will characterize the clinical impact of these findings and whether early chest CT could identify patients at risk for ARDS or other pulmonary complications.

Post-mortem distribution of MDPHP in a fatal intoxication case.

The synthetic cathinone (SC) 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP), is structurally correlated to the 3,4-methylenedioxypyrovalerone (MDPV). In recent years, the number of intoxication cases has increased even if little is known about the pharmacokinetics properties. The post-mortem (PM) distribution of MDPHP remains largely unexplored. In these reports, MDPHP levels were quantified in blood, gastric content and urine. This study aimed to describe the MDPHP PM distribution in several specimens, i.e. central and peripheral blood (CB and PB), right and left vitreous humor (rVH and lVH), gastric content (GCo), urine (U) and hair. The samples were collected from a cocaine-addicted 30-year-old man with a PM interval estimated in 3-4 h. Autopsy examination revealed unspecific findings, i.e. cerebral and pulmonary edema. No injection marks were observed. Toxicological analyses were performed using a multi-analytical approach: headspace gas chromatography for blood alcohol content (BAC); gas chromatography-mass spectrometry (GC-MS) for the main drugs of abuse; liquid chromatography-tandem mass spectrometry (LC-MS/MS) for benzodiazepines and new psychoactive substances (NPS). BAC was negative (0.02 g/L). MDPHP concentrations were: 1,639.99 ng/mL, CB; 1,601.90 ng/mL, PB; 12,954.13 ng/mL, U; 3,028.54 ng/mL, GCo; 1,846.45 ng/mL, rVH; 2,568.01 ng/mL, lVH; 152.38 (0.0-1.5 cm) and 451.33 (1.5-3.0 cm) ng/mg, hair. Moreover, hair segments were also positive for 3,4-dimethylmethcathinone (DMMC < limit of quantification: 0.01 ng/mg), α-PHP (0.59 ng/mg, 0.0-1.5 cm; 3.07 ng/mg, 1.5-3.0 cm), cocaine (6.58 ng/mg, 0.0-1.5 cm; 22.82 ng/mg, 1.5-3.0 cm), and benzoylecgonine (1.13 ng/mg, 0.0-1.5 cm; 4.30 ng/mg, 1.5-3.0 cm). MDPHP concentrations were significantly higher than those reported in the literature for fatal cases. For these reasons, the cause of death was probably the consumption of a lethal amount of MDPHP. Because CB and PB were similar, PM redistribution was not relevant.

Causal relationship between lipidome and acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS), with high morbidity and mortality, is a common clinical syndrome of acute respiratory failure caused by diffuse lung inflammation and edema. ARDS can precipitate in various ways. The complex pathophysiology of ARDS involves the activation and dysregulation of multiple metabolisms and immune responses. Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of 179 genetically predicted lipid species and ARDS (375 cases, 406,518 controls) was performed and validated in plasma and pulmonary edema fluid from 24 patients. Furthermore, we used a two-step MR to quantify the effect of immune cell-mediated lipids on ARDS. We identified 8 lipids (Cholesterol, Phosphatidylcholine (14:0_16:0), Phosphatidylcholine (16:0_20:5), Phosphatidylcholine (18:0_18:2), Phosphatidylethanolamine (18:1_18:1), Triacylglycerol (51:2), Triacylglycerol (52:4), and Triacylglycerol (54:3) ) associated with ARDS. The proportions of genetically-predicted lipids mediated by the four types of immune cells were determined. Sensitivity analysis did not reveal any obvious pleiotropy or heterogeneity. Our study demonstrates the power of multivariate genetic analysis in correlated lipidomic data and reveals genetic links between ARDS and lipid species beyond standard lipids.

Celostna ultrazvočna ocena kongestije pri bolnikih s srčnim popuščanjem – kaj moramo vedeti?

In clinical practice, the assessment of congestion in patients with heart failure is most often based on history, clinical examination, and chest X-ray. Clinical symptoms and signs of congestion or signs of congestion on the radiograph appear only in moderate or severe congestion, which can lead to a delay in the diagnosis and appropriate treatment of patients with heart failure. Ultrasound assessment of pulmonary and systemic venous congestion enables more accurate and early identification of congestion, enables better adjustment of diuretic therapy, and represents an important risk assessment for predicting the treatment outcome in patients with heart failure. For clinical use, ultrasound evaluates systemic venous congestion in the inferior vena cava, internal jugular, hepatic, portal, and interlobar renal veins. In contrast, pulmonary congestion is evaluated with lung ultrasound. Due to the ease of implementation and interpretation, the ultrasound assessment of congestion is accessible to both beginners and those who are not skilled in ultrasound examination of the heart and opens the possibility of using the method to a wide range of doctors who encounter patients with heart failure. In the article, we present individual ultrasound methods for assessing systemic venous and pulmonary congestion, their advantages and disadvantages, and explain the interpretation of the obtained values.

Extraction of clinical data on major pulmonary diseases from unstructured radiologic reports using a large language model.

Despite significant strides in big data technology, extracting information from unstructured clinical data remains a formidable challenge. This study investigated the utility of large language models (LLMs) for extracting clinical data from unstructured radiological reports without additional training. In this retrospective study, 1800 radiologic reports, 600 from each of the three university hospitals, were collected, with seven pulmonary outcomes defined. Three pulmonology-trained specialists discerned the presence or absence of diseases. Data extraction from the reports was executed using Google Gemini Pro 1.0, OpenAI's GPT-3.5, and GPT-4. The gold standard was predicated on agreement between at least two pulmonologists. This study evaluated the performance of the three LLMs in diagnosing seven pulmonary diseases (active tuberculosis, emphysema, interstitial lung disease, lung cancer, pleural effusion, pneumonia, and pulmonary edema) utilizing chest radiography and computed tomography scans. All models exhibited high accuracy (0.85-1.00) for most conditions. GPT-4 consistently outperformed its counterparts, demonstrating a sensitivity of 0.71-1.00; specificity of 0.89-1.00; and accuracy of 0.89 and 0.99 across both modalities, thus underscoring its superior capability in interpreting radiological reports. Notably, the accuracy of pleural effusion and emphysema on chest radiographs and pulmonary edema on chest computed tomography scans reached 0.99. The proficiency of LLMs, particularly GPT-4, in accurately classifying unstructured radiological data hints at their potential as alternatives to the traditional manual chart reviews conducted by clinicians.

Transcriptome analysis revealed that ischemic post-conditioning suppressed the expression of inflammatory genes in lung ischemia-reperfusion injury

IntroductionIschemic post-conditioning (I-post C) is a recognized therapeutic strategy for lung ischemia/reperfusion injury (LIRI). However, the specific mechanisms underlying the lung protection conferred by I-post C remain unclear. This study aimed to investigate the protective mechanisms and potential molecular regulatory networks of I-post C on lung tissue.MethodsTranscriptome analysis was performed on rat lung tissues obtained from Sham, ischemia-reperfusion (IR), and I-post C groups using RNA-seq to identify differentially expressed genes (DEGs). Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted to elucidate significantly enriched pathways in the IR and I-post C groups. Additionally, protein-protein interaction (PPI) network analysis was carried out to examine associations among the DEGs. Pathological changes in lung tissues were assessed using hematoxylin-eosin (H&amp;amp;E) staining. The expression levels of CXCL1 and CXCL6 in the IR and I-post C groups were evaluated through immunofluorescence and Western blotting.ResultsOur results showed that I-post C significantly attenuated both pulmonary edema and inflammatory cell infiltration. Transcriptome analysis identified 38 DEGs in the I-post C group compared to the IR group, comprising 21 upregulated and 17 downregulated genes. Among these, seven inflammation-related DEGs exhibited co-expression patterns with the Sham and IR groups, with notable downregulation of Cxcl1 and Cxcl6. GO analysis primarily linked these DEGs to neutrophil activation, chemotaxis, cytokine activity, and CCR chemokine receptor binding. KEGG analysis revealed enriched pathways, including the IL-17, TNF, and NF-κB signaling pathways. GSEA indicated downregulation of neutrophil chemotaxis and the IL-17 signaling pathway, correlating with reduced expression of Cxcl1 and Cxcl6. Validation of Cxcl1 and Cxcl6 mRNA expression via immunofluorescence and Western blotting supported the RNA-seq findings. Furthermore, a PPI network was constructed to elucidate interactions among the 29 DEGs.ConclusionsThrough RNA-Seq analysis, we concluded that I-post C may reduce inflammation and suppress the IL-17 signaling pathway, thereby protecting against lung damage caused by LIRI, potentially involving neutrophil extracellular traps.

Impact of Fluid Balance on the Development of Lung Injury.

The pathophysiological relationship between fluid administration, fluid balance, and mechanical ventilation in the development of lung injury is unclear. To quantify the relative contribution of mechanical power and fluid balance in the development of lung injury. Thirty-nine healthy female pigs, divided into four groups, were ventilated for 48 hours with high (~18J/min) or low (~6J/min) mechanical power; and high (~4L) or low (~1L) targeted fluid balance. We measured physiological variables e.g., end-expiratory lung gas volume, respiratory-system mechanics, gas-exchange and hemodynamics, and pathological variables, i.e., lung weight, wet-to-dry ratio, and histology score of lung injury. End-expiratory lung gas volume, respiratory system elastance, strain and oxygenation significantly worsened in the two groups assigned to receive high fluid balance, irrespective of the mechanical power received. All four groups had similar lung weight (i.e., lung edema), lung wet-to-dry ratio and pathological variables. Animals with higher fluid balance developed more ascites, which was associated with a decrease in end-expiratory lung gas volume. In conclusion, our study did not detect a significant difference in lung injury between high and low mechanical power. Some damage is directly attributable to mechanical power, while additional injury appears to result indirectly from high fluid balance, which reduces end-expiratory lung gas volume, with ascites playing an important role in this process.

Impact of vitamin D on hyperoxic acute lung injury in neonatal mice

BackgroundProlonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice.MethodsC57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O2) conditions for 6 days. Control, low (5 ng/neonate) and high (25 ng/neonate) doses of VitD were administered daily beginning at day 2 via oral gavage. Lung tissue was analyzed for edema, changes in pulmonary structure and function, and inflammatory cytokine expression.ResultsNeonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant changes in cytokine expression were observed between untreated and VitD neonates. While changes in surfactant protein mRNA expression were impacted by hyperoxia and VitD administration, no significant changes in alveolar type II cell percentages were observed. At 3 weeks, mice in hyperoxia treated with VitD had greater lung compliance, diminished airway reactivity and improved weight gain.ConclusionsHigh dose VitD significantly limited harmful effects of HALI. These results suggest that supplementation of VitD to neonatal mice during hyperoxia exposure provides both short-term and long-term protective benefits against HALI.

Design, synthesis and bioactivity evaluation of cinnamic acid derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury

Acute lung injury (ALI), a common critical disease in clinical practice, has a mortality rate as high as 30–40 %, yet currently, no effective treatment methods are available. Research on ALI indicated that inhibition of overexpressed inflammatory factors might be a potential treatment for ALI. In this study, a series of cinnamic acid derivatives were obtained by introducing diverse aminothiazole fragments into the natural product cinnamic acid. Among these derivatives, compound 22 displayed excellent activity of inhibiting the release of IL-6 in J774A.1 cells. Moreover, it also ameliorated the LPS-induced ALI in mouse model by suppressing cytokine expression, reducing lung edema and macrophage infiltration. These findings indicated that compound 22 might provide a new lead structure for the development of drugs for ALI.

Evaluating the use of tunneled hemodialysis catheters in the treatment of acute kidney disease patients requiring hemodialysis: a case-control study.

Tunneled hemodialysis catheters (TDCs) are increasingly used in the emergency management of severe acute kidney disease (AKD). This study aimed to evaluate the effectiveness of TDCs in AKD patients requiring hemodialysis. A case-control study was conducted in Khartoum, Sudan between February and September 2020. Adult patients admitted to the Baraha Medical City Intensive Care Unit with AKD due to non-infectious causes, and requiring hemodialysis were enrolled. Patients were randomly assigned to undergo hemodialysis using either tunneled or non-tunneled hemodialysis catheters (NTDCs). The performance and complications associated with TDCs were assessed during the hospital stay, after discharge, and until catheter removal. Data were analyzed using SPSS. A total of 122 patients with a mean age of 60.4 ± 5.7years were included. AKD was primarily due to acute tubular necrosis (67.2%) and interstitial nephritis (16.4%). Indications for hemodialysis were mostly acute pulmonary edema (64.8%) and symptomatic uremia (27.9%). TDCs were used in 54 (44.3%) patients, while NTDCs were used in 68 (55.7%). The right internal jugular vein was the most common insertion site (95.9%). TDCs were associated with significantly higher blood flow (P < 0.0001) and lower rates of exit site infections (P = 0.034), catheter-related bacteremia (P = 0.011), and catheter malfunction (P = 0.001). They showed a significantly longer functional duration compared to NTDCs (P < 0.0001). TDCs appear to be a safer and more effective option for AKD patients requiring urgent and prolonged hemodialysis, with fewer complications and longer catheter function.

Galectin-3 disrupts tight junctions of airway epithelial cell monolayers by inducing expression and release of matrix metalloproteinases upon influenza a infection.

Galectins are β-galactosyl-binding lectins with key roles in early development, immune regulation, and infectious disease. Influenza A virus (IAV) infects the airway epithelia, and in severe cases may lead to bacterial superinfections and hypercytokinemia, and eventually, to acute respiratory distress syndrome (ARDS) through the breakdown of airway barriers. The detailed mechanisms involved, however, remain poorly understood. Our prior in vivo studies in a murine model system revealed that upon experimental IAV and pneumococcal primary and secondary challenges, respectively, galectin-1 and galectin-3 (Gal-3) are released into the airway and bind to the epithelium that has been desialylated by the viral neuraminidase, contributing to secondary bacterial infection and hypercytokinemia leading to the clinical decline and death of the animals. Here we report the results of in vitro studies that reveal the role of the extracellular Gal-3 in additional detrimental effects on the host by disrupting the integrity of the airway epithelial barrier. IAV infection of the human airway epithelia cell line A549 increased release of Gal-3 and its binding to the A549 desialylated cell surface, notably to the transmembrane signaling receptors CD147 and integrin-β1. Addition of recombinant Gal-3 to A549 monolayers resulted in enhanced expression and release of matrix metalloproteinases, leading to disruption of cell-cell tight junctions, and a significant increase in paracellular permeability. This study reveals a critical mechanism involving Gal-3 that may significantly contribute to the severity of IAV infections by promoting disruption of tight junctions and enhanced permeability of the airway epithelia, potentially leading to lung edema and ARDS.

Useful central mechanical circulatory support system for critical biventricular heart failure associated with high pulmonary vascular resistance.

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) is a powerful life-saving tool; however, it can sometimes induce severe pulmonary edema in patients with critical heart failure. We report favorable outcomes in critically ill patients by using a central ECMO system with an innovative blood perfusion method. We analyzed 10 patients with severe heart failure and pulmonary edema who were treated with the central ECMO system at our institution between April 2022 and October 2023. The system consists of central cannulation with two inflows from the right atrium and left ventricle, and two outflows to the aorta and pulmonary artery, connected by two Y-connectors to a single ECMO circuit (RALV-AOPA ECMO). In this system, blood flow to the pulmonary artery is adjusted and mean pulmonary artery pressure is limited to <20 mm Hg, which reduces right ventricular afterload and prevents the worsening of pulmonary edema and hemorrhage. Six patients were diagnosed with fulminant lymphocytic myocarditis, and four were diagnosed with coronavirus disease 2019-related myocardial injury. The ejection fraction was 6.5 ± 4.1%. The average intraoperative pulmonary vascular resistance was 4.6 ± 1.3 Wood units. After 24 h, the mean pulmonary arterial pressure was 12.8 ± 4.3 mm Hg, and pulmonary vascular resistance was 1.5 ± 0.3 Wood units. The duration of central RALV-AOPA ECMO was 3.7 ± 2.1 days. Finally, six patients were weaned, three received HeartMate3, and one received heart transplantation. At follow-up, all patients remained alive (428 ± 208 days), and two patients experienced cerebrovascular accidents without any lasting sequelae. The central RALV-AOPA ECMO is an innovative system that achieves early improvement in pulmonary vascular resistance and is safe and feasible for patients with acute biventricular failure and pulmonary edema.

Neurogenic pulmonary edema caused by epileptic attack: a case report

Neurogenic pulmonary edema (NPE) is a life-threatening situation that progresses with acute respiratory distress caused by central neurological damage or injury. NPE may occur as a result of different central nervous system diseases and disorders, such as brain malignancies, traumatic brain injuries, infections, and convulsions. This case report was designed to highlight the causes, outcome, and treatment of NPE triggered by an epileptic attack.

Left ventricle unloading during veno-arterial extracorporeal membrane oxygenation: review with updated evidence.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to treat medically refractory cardiogenic shock and cardiac arrest, and its usage has increased exponentially over time. Although VA-ECMO has many advantages over other mechanical circulatory supports, it has the unavoidable disadvantage of increasing retrograde arterial flow in the afterload, which causes left ventricular (LV) overload and can lead to undesirable consequences during VA-ECMO treatment. Weak or no antegrade flow without sufficient opening of the aortic valve increases the LV end-diastolic pressure, and that can cause refractory pulmonary edema, blood stagnation, thrombosis, and refractory ventricular arrhythmia. This hemodynamic change is also related to an increase in myocardial energy consumption and poor recovery, making LV unloading an essential management issue during VA-ECMO treatment. The principal factors in effective LV unloading are its timing, indications, and modalities. In this article, we review why LV unloading is required, when it is indicated, and how it can be achieved.