Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure

Sci Rep. 2015 Apr 13:5:9704. doi: 10.1038/srep09704.

Abstract

Treatment of decompensated heart failure often includes administration of levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in heart failure. We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course. Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 ± 31.1 pmol/l at baseline to 215.02 ± 27.96 pmol/l at 6 h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 ± 1.4-fold increase at baseline vs. 6.0 ± 1.1-fold increase with levosimendan). MPO levels also significantly correlated with diastolic blood pressure over the time course. In a multivariate linear model, the main contributor to systolic, diastolic and mean blood pressure was level of PMN elastase. MPO contributed only in heparin-treated patients, suggesting a more significant role for endothelial-bound MPO than for circulating MPO or elastase with respect to blood pressure regulation. We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients. This mechanism may regulate endothelial function and vascular tone in heart failure patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomarkers
  • Blood Pressure / drug effects
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Cell Degranulation / drug effects
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / etiology
  • Heart Failure / metabolism*
  • Heart Failure / mortality
  • Humans
  • Hydrazones / pharmacology
  • Hydrazones / therapeutic use*
  • Inflammation / metabolism
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Nitric Oxide / metabolism
  • Peroxidase / metabolism*
  • Pyridazines / pharmacology
  • Pyridazines / therapeutic use*
  • Severity of Illness Index
  • Simendan
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cardiotonic Agents
  • Hydrazones
  • Pyridazines
  • Nitric Oxide
  • Simendan
  • Peroxidase