title: In contrast to its anti-inflammatory and anti-apoptotic peripheral effect, levosimendan failed to induce a long-term neuroprotective effect in a rat model of mild septic encephalopathy: a pilot study.
abstract: Levosimendan shows protective myocardial characteristics and is administered to enhance cardiac contractility in patients. However, currently little is known about levosimendan's effect on brain. The aim of this pilot study was to investigate the long-term effect of levosimendan on brain and during mild rat sepsis in comparison to its peripheral mode of action. Adult rats (n=40) were divided into four groups with n=10 per group: (I) sham, (II) levosimendan (283 μg/kg body weight i.v.), (III) lipopolysaccharide (LPS, 8 mg/kg body weight i.p.), and (IV) LPS+levosimendan. Levosimendan was given 24h after injecting LPS. Psychometric investigations were conducted using a Morris water maze (MWM) and a holeboard test. In cerebral and splenic tissue, IL-1β, Il-6, TNFalpha levels, and apoptosis were determined; cerebral tissue corticosterone concentration was measured 6 days after injecting LPS. Blood cytokine concentrations were determined 1 day and 6 days after injecting LPS. Rats that received an LPS injection spent more time in the outer zone of the MWM according to increased cerebral corticosterone levels, and showed decreased cognitive abilities. LPS induced a reduction in body weight, increased splenic apoptosis and blood cytokine level. Levosimendan showed anti-inflammatory and anti-apoptotic properties in spleen but failed to show a long-term neuroprotective effect.
authors.affiliation: Department of Anesthesiology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Electronic address: konstanze.plaschke@med.uni-heidelberg.de.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Plaschke
authors.affiliation: Department of Anesthesiology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Bent
authors.affiliation: Department of Anesthesiology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Internal Medicine, Laboratory Medicine, University of Heidelberg, Im Neuenheimer Feld 671, D-69120 Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.affiliation: Department of Pathology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 224, D-69120 Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kopitz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D003345:Corticosterone / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010865:Pilot Projects; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar; D000077464:Simendan; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006835:Hydrazones; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D011724:Pyridazines; D000077464:Simendan; D003345:Corticosterone
keywords: Cognition; Endotoxinemia; Inflammation; LPS; Levosimendan; Neuroprotection