title: Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure.
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.
authors: Stanford University, Division of Cardiovascular Medicine, Stanford, CA, USA.
authors: Matti
authors: M
authors: Adam
authors: 1] University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands [2] European Medical School Oldenburg-Groningen, Heart Center Oldenburg, Department of Cardiology, Oldenburg, Germany.
authors: Sven
authors: S
authors: Meyer
authors: University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
authors: Henning
authors: H
authors: Knors
authors: University of Cologne, Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, Cologne, Germany.
authors: Anna
authors: A
authors: Klinke
authors: University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
authors: Ulf K
authors: UK
authors: Radunski
authors: University of Cologne, Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, Cologne, Germany.
authors: Tanja K
authors: TK
authors: Rudolph
authors: University of Cologne, Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, Cologne, Germany.
authors: Volker
authors: V
authors: Rudolph
authors: Stanford University, Division of Cardiovascular Medicine, Stanford, CA, USA.
authors: Joshua M
authors: JM
authors: Spin
authors: Stanford University, Division of Cardiovascular Medicine, Stanford, CA, USA.
authors: Philip S
authors: PS
authors: Tsao
authors: University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
authors: Angelika
authors: A
authors: Costard-Jäckle
authors: University of Cologne, Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, Cologne, Germany.
authors: Stephan
authors: S
authors: Baldus
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015550:Cell Degranulation / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000077464:Simendan; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D009569:Nitric Oxide; D000077464:Simendan; D009195:Peroxidase