ArticleCritical care (London, England)2011
Levosimendan inhibits release of reactive oxygen species in polymorphonuclear leukocytes in vitro and in patients with acute heart failure and septic shock: a prospective observational study.
Article in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Comparative efficacy of levosimendan and dobutamine in sepsis-related cardiac impairment: a meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery: An Update Meta-Analysis and Trial Sequential Analysis.BioMed research international · 2018Pooled it
- Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017 : Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine.Intensive care medicine · 2017Pooled it
- Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial.Intensive care medicine · 2019Trial
- Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomized Controlled Pilot Study.Shock (Augusta, Ga.) · 2017Trial
- Effect of small-dose levosimendan on mortality rates and organ functions in Chinese elderly patients with sepsis.Clinical interventions in aging · 2017Trial
- Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial.Medical science monitor : international medical journal of experimental and clinical research · 2016Trial
- Trial
- To the Editor: Levosimendan in sepsis-induced cardiac dysfunction: consolidating evidence within a complex clinical landscape.European journal of clinical pharmacology · 2026Article
- Perioperative use of levosimendan in complex congenital heart disease management.European journal of pediatrics · 2026Article
- Levosimendan vs. Dobutamine in Patients with Septic Shock: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.Journal of clinical medicine · 2025Review
- Levosimendan versus dobutamine in septic cardiomyopathy: a randomized clinical trial on cardiac function and safety.Frontiers in cardiovascular medicine · 2025Article
- Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling.Biomedicines · 2024Article
- Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.Biomolecules · 2023Review
- STAT3 Suppresses Cardiomyocytes Apoptosis in CVB3-Induced Myocarditis Via Survivin.Frontiers in pharmacology · 2020Article
- Primary graft dysfunction after heart transplantation: a thorn amongst the roses.Heart failure reviews · 2019Review
- Shock - Classification and Pathophysiological Principles of Therapeutics.Current cardiology reviews · 2019Review
- Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways.Frontiers in pharmacology · 2018Article
- Effects of levosimendan on mortality in patients with septic shock: systematic review with meta-analysis and trial sequential analysis.Oncotarget · 2017Article
- Acute Right Ventricular Dysfunction in Intensive Care Unit.BioMed research international · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionLevosimendan is an extensively investigated inodilator showing also cardioprotective and antiinflammatory effects. The aim of our study was to explore the influence of levosimendan on polymorphonuclear leucocytes (PMN), a main source of reactive oxygen species, in vitro and in patients with acute heart failure or septic myocardial depression.
methodsPMN isolated from healthy volunteers were incubated with levosimendan in vitro. After stimulation with N-formyl-Met-Leu-Phe (fMLP) or phorbol 12-myristate 13-acetate (PMA) respiratory burst was quantified using a fluorescent dye. Apoptosis and expression of cell adhesion molecules of PMN were measured by flow cytometry. For determination of in vivo effects patients with acute heart failure (n = 16) or septic cardiac failure (n = 9) receiving levosimendan treatment were enrolled consecutively. PMN were isolated to measure respiratory burst activity before treatment as well as one and two hours after initiation of levosimendan administration. Furthermore inflammatory, hemodynamic and renal function parameters were obtained.
resultsIn vitro, levosimendan suppressed respiratory burst activity in fMLP or PMA stimulated PMN in a dose dependent manner by 30 ± 11% (P < 0.001) at 100 ng/mL and by 27 ± 17% (P < 0.001) at 1000 ng/mL respectively. Markers of apoptosis and PMN cell adhesion molecule expression remained unaffected by levosimendan treatment.In vivo, levosimendan treatment for two hours resulted in a significant reduction of PMA stimulated oxidative burst by 45% (P < 0.01) and fMLP stimulated oxidative burst by 49% (P < 0.05) in patients with acute heart failure. In patients suffering from septic shock levosimendan treatment decreased oxidative burst activity in unstimulated, fMLP and PMA stimulated PMN by 48% (P < 0.05), 46% (P < 0.01) and 43% (P < 0.01) respectively.
conclusionsLevosimendan appears to exert distinct immunomodulatory effects by decreasing oxidative burst activity of PMN. This property might contribute to the previously described cardioprotective effects of the drug.
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