title: No beneficial effects of levosimendan in acute porcine endotoxaemia.
abstract: BACKGROUND
  Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis-induced heart failure and haemodynamic derangements. Its use in this setting is, however, still not well investigated. The aim of this study was to test the hypothesis that levosimendan is able to attenuate endotoxin-induced pulmonary hypertension and improve myocardial function in a porcine model. The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response.
  
  
  METHODS
  Endotoxaemia was induced in 18 pigs, randomized to placebo and Levosimendan groups. All pigs were fluid resuscitated and Noradrenalin infusion was given according to a predefined protocol. Systemic haemodynamics and myocardial function were measured using pulmonary artery catheterization and transthoracic echocardiography. Renal and liver function tests and cytokine concentrations were measured in plasma.
  
  
  RESULTS
  Levosimendan did not attenuate endotoxin-induced pulmonary hypertension and did not improve myocardial function. There were no differences in renal or liver function. Increases in arterial lactate and decreases in base excess were observed in the Levosimendan group, as well as significant increases in plasma interleukin (IL)-6 and IL-8.
  
  
  CONCLUSIONS
  Contrary to our hypothesis, levosimendan given in conjunction with a protocolized vasopressor and fluid resuscitation did not improve cardiac, renal or liver function in this model of acute porcine endotoxaemia. Hyperlactataemia, acidosis and increases in plasma pro-inflammatory cytokines were observed, the mechanisms and implications of which remain unclear.
authors.affiliation: Department of Intensive Care Medicine, Skåne University Hospital Malmö, Lund University, Sweden. michelle.chew@med.lu.se
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Chew
authors.forename: W J
authors.initials: WJ
authors.lastname: Hawthorne
authors.forename: J
authors.initials: J
authors.lastname: Bendall
authors.forename: S
authors.initials: S
authors.lastname: Whereat
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: I
authors.initials: I
authors.lastname: Ting
authors.forename: D
authors.initials: D
authors.lastname: Simond
authors.forename: A
authors.initials: A
authors.lastname: McLean
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004452:Echocardiography; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D006835:Hydrazones / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D007677:Kidney Function Tests; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008111:Liver Function Tests; D011652:Pulmonary Circulation / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000502:physiology; D018401:Sample Size; D000077464:Simendan; D013552:Swine; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D006835:Hydrazones; D008070:Lipopolysaccharides; D011724:Pyridazines; D019344:Lactic Acid; D000077464:Simendan