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

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.

• Publication year

  2011

• Venue

  Critical Care

• Publication date

  2011-07-12

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/cc10307PMID 21749676PMCID 3387603
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Effects of Levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure.

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• Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure.

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• Regional anaesthesia

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• 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

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• Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm.

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• Acute Hemodynamic and Clinical Effects of Levosimendan in Patients With Severe Heart Failure

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• Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium.

  1998cited by this paper
• Vasoactive drugs inhibit oxygen radical production of neutrophils.

  1997cited by this paper
• Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart.

  1995cited by this paper
• Leucocyte-endothelial interactions and regulation of leucocyte migration.

  1994cited by this paper
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• Depolarization blunts the oxidative burst of human neutrophils. Parallel effects of monoclonal antibodies, depolarizing buffers, and glycolytic inhibitors.

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  1987cited by this paper
• Human neutrophils increase expression of C3bi as well as C3b receptors upon activation.

  1984cited by this paper

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• [Acute kidney injury].

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