Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure
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Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure. / Adam, Matti; Meyer, Sven; Knors, Henning; Klinke, Anna; Radunski, Ulf K; Rudolph, Tanja K; Rudolph, Volker; Spin, Joshua M; Tsao, Philip S; Costard-Jäckle, Angelika; Baldus, Stephan.
in: SCI REP-UK, Jahrgang 5, 13.04.2015, S. 9704.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure
AU - Adam, Matti
AU - Meyer, Sven
AU - Knors, Henning
AU - Klinke, Anna
AU - Radunski, Ulf K
AU - Rudolph, Tanja K
AU - Rudolph, Volker
AU - Spin, Joshua M
AU - Tsao, Philip S
AU - Costard-Jäckle, Angelika
AU - Baldus, Stephan
PY - 2015/4/13
Y1 - 2015/4/13
N2 - 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.
AB - 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.
KW - Anti-Inflammatory Agents/pharmacology
KW - Biomarkers
KW - Blood Pressure/drug effects
KW - Cardiotonic Agents/pharmacology
KW - Cell Degranulation/drug effects
KW - Female
KW - Heart Failure/diagnosis
KW - Humans
KW - Hydrazones/pharmacology
KW - Inflammation/metabolism
KW - Leukocytes/drug effects
KW - Male
KW - Middle Aged
KW - Neutrophils/drug effects
KW - Nitric Oxide/metabolism
KW - Peroxidase/metabolism
KW - Pyridazines/pharmacology
KW - Severity of Illness Index
KW - Simendan
KW - Time Factors
U2 - 10.1038/srep09704
DO - 10.1038/srep09704
M3 - SCORING: Journal article
C2 - 25867530
VL - 5
SP - 9704
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -