title: Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study.
abstract: OBJECTIVE
  To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock.
  
  
  METHODS
  Prospective, controlled experimental study.
  
  
  METHODS
  University-based research laboratory.
  
  
  METHODS
  Nineteen anesthetized, mechanically ventilated sheep.
  
  
  METHODS
  Endotoxin-treated sheep were randomly assigned to three groups: control (n=7), dobutamine (10 microg/kg/min, n=6) and levosimendan (100 microg/kg over 10 min followed by 100 microg/kg/h, n=6) and treated for 120 min.
  
  
  RESULTS
  After endotoxin administration, systemic and intestinal DO(2) decreased (24.6+/-5.2 vs 15.3+/-3.4 ml/kg/min and 105.0+/-28.1 vs 55.8+/-25.9 ml/kg/min, respectively; p<0.05 for both). Arterial lactate and the intramucosal-arterial PCO(2) difference (DeltaPCO(2)) increased (1.4+/-0.3 vs 3.1+/-1.5 mmHg and 9+/-6 vs 23+/-6 mmHg mmol/l, respectively; p<0.05). Systemic DO(2) was preserved in the dobutamine-treated group (22.3+/-4.7 vs 26.8+/-7.0 ml/min/kg, p=NS) but intestinal DO(2) decreased (98.9+/-0.2 vs 68.0+/-22.9 ml/min/kg, p<0.05) and DeltaPCO(2) increased (12+/-5 vs 25+/-11 mmHg, p<0.05). The administration of levosimendan prevented declines in systemic and intestinal DO(2) (25.1+/-3.0 vs 24.0+/-6.3 ml/min/kg and 111.1+/-18.0 vs 98.2+/-23.1 ml/min/kg, p=NS for both) or increases in DeltaPCO(2) (7+/-7 vs 10+/-8, p=NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6+/-0.3 vs 2.5+/-0.7 and 1.4+/-0.4 vs. 2.9+/-1.1 mmol/l, p=NS between groups).
  
  
  CONCLUSIONS
  Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.
authors.affiliation: Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 42 No 577, 1900, La Plata, Argentina. arnaldodubin@speedy.com.ar
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Dubin
authors.forename: Gastón
authors.initials: G
authors.lastname: Murias
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Sottile
authors.forename: Mario Omar
authors.initials: MO
authors.lastname: Pozo
authors.forename: Marcelo
authors.initials: M
authors.lastname: Barán
authors.forename: Vanina Siham Kanoore
authors.initials: VS
authors.lastname: Edul
authors.forename: Héctor Saúl
authors.initials: HS
authors.lastname: Canales
authors.forename: Graciela
authors.initials: G
authors.lastname: Etcheverry
authors.forename: Bernardo
authors.initials: B
authors.lastname: Maskin
authors.forename: Elisa
authors.initials: E
authors.lastname: Estenssoro
mesh_terms: D000138:Acidosis / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004280:Dobutamine / Q000494:pharmacology; D019446:Endotoxemia / Q000188:drug therapy; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D019344:Lactic Acid / Q000097:blood; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy*; D000077464:Simendan; D013152:Splanchnic Circulation / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019344:Lactic Acid; D000077464:Simendan; D004280:Dobutamine; D010100:Oxygen