The role of hemoadsorption in cardiac surgery – a systematic review

BMC Cardiovascular Disorders, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 18, 2024

Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with emergence of new adsorptive devices, hemoadsorption increasingly applied during CPB cardiac surgery, for patients at different inflammatory risks, or postoperative complications. Clinical evidence so far not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess role perioperative by summarizing knowledge clinical setting.

Language: Английский

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Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury

Redox Biology, Journal Year: 2024, Volume and Issue: 74, P. 103231 - 103231

Published: June 7, 2024

Primary graft dysfunction (PGD) is a severe form of acute lung injury resulting from ischemia/reperfusion (I/R) in transplantation (LTx), associated with elevated post-transplant morbidity and mortality rates. Neutrophils infiltrating during reperfusion are identified as pivotal contributors to I/R by releasing excessive neutrophil extracellular traps (NETs) via NETosis. While alveolar macrophages (AMs) involved regulating chemotaxis infiltration, their role NETosis remains inadequately elucidated. Extracellular histones constitute the main structure NETs can activate AMs. In this study, we confirmed significant involvement histone-induced M1 phenotype AMs (M1-AMs) driving I/R. Using secretome analysis, public protein databases, transwell co-culture models neutrophils, Cathepsin C (CTSC) derived major mediator Further elucidating molecular mechanisms, found that CTSC induced through pathway dependent on NADPH oxidase-mediated production reactive oxygen species (ROS). could significantly p38 MAPK, phosphorylation oxidase subunit p47phox, thereby facilitating trafficking cytoplasmic subunits cell membrane activating oxidase. Moreover, up-regulated activated its substrate proteinase 3 (mPR3), an increased release NETosis-related inflammatory factors. Inhibiting revealed great potential mitigating These findings suggests may be crucial factor mediating I/R, targeting inhition represent novel intervention for PGD LTx.

Language: Английский

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Identification of Neutrophil Extracellular Trap-Related Gene Expression Signatures in Ischemia Reperfusion Injury During Lung Transplantation: A Transcriptome Analysis and Clinical Validation

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 981 - 1001

Published: Feb. 1, 2024

Purpose: Ischemia reperfusion injury (IRI) unavoidably occurs during lung transplantation, further contributing to primary graft dysfunction (PGD). Neutrophils are the end effectors of IRI and activated neutrophils release neutrophil extracellular traps (NETs) amplify damage. Nevertheless, potential contributions NETs in remain incompletely understood. This study aimed explore NET-related gene biomarkers transplantation. Methods: Differential expression analysis was applied identify differentially expressed genes (DEGs) for transplantation based on matrix data (GSE145989, 127003) downloaded from GEO database. The CIBERSORT weighted co-expression network (WGCNA) algorithms were utilized key modules associated with infiltration. Moreover, least absolute shrinkage selection operator regression random forest NET-associated hub genes. Subsequently, screened underwent validation an external dataset (GSE18995) nomogram model. Based clinical peripheral blood samples, immunofluorescence staining dsDNA quantification used assess NET formation, ELISA validate Results: Thirty-eight resulted intersection between 586 DEGs 75 brown module genes, primarily enriched leukocyte migration formation. four candidate (FCAR, MMP9, PADI4, S100A12) out via machine learning algorithms. Validation using model achieved better predictive value. Substantial formation demonstrated IRI, more pronounced observed patients PGD ≥ 2. S100A12, MMP9 all confirmed be up-regulated after through ELISA, higher levels S100A12 2 compared non-PGD patients. Conclusion: We identified three that provide new insights into early detection therapeutic targets Keywords: ischemia injury, traps, dysfunction, WGCNA,

Language: Английский

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Prolonged dialysis during ex vivo lung perfusion promotes inflammatory responses

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 22, 2024

lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in perfusate and, as a corrective measure, costly repeatedly replaced during standard care procedure. As an interesting alternative, hemodialyzer could be placed on circuit, which was previously shown rebalance composition and maintain function viability appearing impact global gene expression lung. Here, we assessed biological effects performing biochemical refined functional genomic analyses over 12h procedure pig model. We found that dialysis stabilized electrolytic parameters but enhanced protein several inflammatory cytokines promoted profile predicting higher endothelial activation already 6h immune cytokine signaling 12h. Therefore, epuration with dialyzer, while correcting features maintaining respiratory function, promotes responses tissue. This finding suggests modifying metabolite can have detrimental tissue response this strategy should not transferred such clinic.

Language: Английский

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Use of intraoperative haemoadsorption in patients undergoing heart transplantation: a proof‐of‐concept randomized trial

ESC Heart Failure, Journal Year: 2023, Volume and Issue: 11(2), P. 772 - 782

Published: Dec. 19, 2023

Abstract Aims The aim of this trial was to compare the clinical effects intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT). Methods and results In a randomized, controlled trial, OHT recipients were randomized receive or care. Outcomes vasoactive‐inotropic score (VIS), frequency vasoplegic syndrome (VS) first 24 h; post‐operative change procalcitonin (PCT) C‐reactive protein (CRP) levels; mycophenolic acid (MPA) concentration; organ dysfunction, major complications, adverse immunological events length in‐hospital stay 1‐year survival. Sixty (haemoadsorption group N = 30, control 25 plus 5 exclusions). Patients had lower median VIS rate VS (VIS: 27.2 [14.6–47.7] vs. 41.9 [22.4–63.2], P 0.046, VS: 20.0% 48.0%, 0.028, respectively), 6.4‐fold decrease odds early (OR: 0.156, CI: 0.029–0.830, 0.029), PCT levels, shorter mechanical ventilation (MV: [19–68.8] hours 65 [23–287] hours, 0.025, respectively) intensive unit (ICU stay: 8.5 [8.0–10.3] days 12 [8.5–18.0] days, 0.022, than group. experienced rates acute kidney injury (AKI: 36.7% 76.0%, 0.004, renal replacement therapy (RRT: 0% 16.0%, 0.037, per cent bilirubin level (PCB: 2.5 [−24.6 71.1] % 72.1 [11.2–191.4] %, 0.009, during period. MPA concentrations measured at pre‐defined time points comparable compared groups (MPA pre‐cardiopulmonary bypass: 2.4 [1.15–3.60] μg/mL 1.6 [1.20–3.20] μg/mL, 0.780, 120 min after cardiopulmonary bypass start: 1.1 [0.58–2.32] 0.9 [0.45–2.10] 0.786). cardiac allograft rejection, 30‐day mortality survival similar between groups. Conclusions Intraoperative associated with better haemodynamic stability, mitigated response, AKI RRT, more stable hepatic excretion, durations MV ICU stay. did not show any relevant adsorption effect on MPA. There no increase rejection related use.

Language: Английский

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Xenotransplantation of Mitochondria: A Novel Strategy to Alleviate Ischemia-Reperfusion Injury during Ex Vivo Lung Perfusion

The Journal of Heart and Lung Transplantation, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce incidence PGD is mitochondrial In this study, we explored delivery isolated mitochondria 4 hour ex vivo perfusion (EVLP) as means mitigate IRI. To provide fresh viable source mitochondria, well streamline workflow without need for muscle biopsies, investigated impact autologous, allogeneic xenogeneic settings, from mouse liver were utilized while autologous sources came pig skeletal biopsies. Treatment with increased P/F ratio reduced pulmonary peak pressure lungs during EVLP, compared any transplantation, indicating IRI mitigation. Extensive investigations using advanced light scanning electron microscopy did not reveal evidence acute rejection groups, safe xenotransplantation mitochondria. Future work needed further explore therapy combating where may serve fresh,

Language: Английский

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Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 2, 2023

In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) line with devices treatments yielded promising results within preclinical clinical studies, potential improve quality. Its main benefit is render marginal declined donor lungs suitable for transplantation, ultimately increasing pool available transplantation. addition, using such therapies machine could also increase time, facilitating logistical planning. Cytokine adsorption been demonstrated as a potentially safe effective therapy when applied EVLP circuit post-transplantation. However, mechanism by which this improves on molecular basis not yet fully understood.We hypothesized that there were characteristic inflammatory immunomodulatory differences between treated without cytokine adsorption, reflecting proteomic changes gene ontology pathways across inflammation-related proteins. study, we investigate mechanisms signaling how impacts function used during post-transplantation hemoperfusion porcine model. Lung tissues post-lung transplantation analyzed their profiles mass spectrometry.We found through set enrichment analysis immune processes coagulation significantly affected treatment after transplantation.In conclusion, showed are approach behind previously reported effects compared non-treated transplant recipients undergoing EVLP.

Language: Английский

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Mitigating the risk of inflammatory type primary graft dysfunction by applying an integrated approach to assess, modify and match risk factors in lung transplantation

Frontiers in Transplantation, Journal Year: 2024, Volume and Issue: 3

Published: Aug. 20, 2024

Long-term outcome following lung transplantation remains one of the poorest all solid organ transplants with a 1- and 5-year survival 85% 59% respectively for adult transplant recipients 50% patients developing chronic allograft dysfunction (CLAD) in first 5 years transplant. Reducing risk inflammatory type primary graft (PGD) is vital improving both short-term long-term due to association early inflammatory-mediated damage CLAD. PGD has multifactorial aetiology high-grade inflammatory-type result cumulative insults that may be incurred or more three variables continuum: donor lungs, recipient intraoperative process. We set out conceptual framework which uses fully integrated approach this continuum attempt identify and, where possible, modify specific donor, goal reducing an individual recipient. also consider concept risk-benefit matching allografts on basis PGD-risk compatibility. The use ex vivo perfusion (EVLP) extended preservation EVLP will explored as safe, non-injurious enable extensive testing lungs potential provide platform targeted therapeutic interventions allografts.

Language: Английский

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Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial

JMIR Research Protocols, Journal Year: 2023, Volume and Issue: 12, P. e52553 - e52553

Published: Oct. 2, 2023

Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains leading cause of early mortality and precipitates chronic allograft dysfunction, main factor in late after LTx. PGD develops within first 72 hours impairs oxygenation capacity lung, measured as partial pressure oxygen (PaO2)/fraction inspired (FiO2). Increasing PaO2/FiO2 ratio thus critical has an impact on survival. There a general lack effective treatments PGD. When transplanted not accepted by immune system recipient, systemic inflammatory response starts where cytokines play role initiating, amplifying, maintaining inflammation to Cytokine filtration can remove these from circulation, reducing inflammation. In proof-of-concept preclinical porcine model LTx, cytokine improved decreased feasibility study, we successfully treated patients undergoing LTx with (ClinicalTrials.gov; NCT05242289).The purpose this clinical trial demonstrate superiority improving outcome, based its effects ratio, plasma levels markers, incidence severity, function, kidney survival, quality life compared standard no filtration.This study Swedish national interventional randomized controlled involving 116 patients. Its objective investigate potential benefits when used conjunction Specifically, aims determine whether application filtration, administered duration 12 initial 24 following procedure, lead patient outcomes. This seeks assess various aspects recovery overall health ascertain positive intervention posttransplantation course.The process recruitment scheduled commence subsequent site initiation visit, which was slated take place August 28, 2023. The outcome measure that will be assessed research endeavor metric denoted highest achieved 72-hour timeframe their procedure.We propose could enhance outcomes Our hypothesis suggests improvements care.ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950.PRR1-10.2196/52553.

Language: Английский

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Hemoadsorption in Organ Preservation and Transplantation: A Narrative Review

Published: Nov. 1, 2023

Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such cytokine storm activation, blood immuno- and AB0- incompatibilities but also be performed for the treatment various life-threatening conditions, as sepsis, acute respiratory distress syndrome (ARDS), cardiogenic shock, all which contribute to adverse clinical outcomes during transplantation. After surgery, dysmetabolism stress response limit successful graft survival lead primary (PGD) or secondary dysfunction. In this context, given that a major problem in transplant medicine is demand organs far exceeds supply, technological innovation hemoadsoption system could greatly increasing number usable organ donors. The objectives review are describe specific advantages disadvantages application context examine, before and/or after transplantation, benefits addition complementary therapy protocol.

Language: Английский

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