title: Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock.
abstract: OBJECTIVE
  To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock.
  
  
  METHODS
  Controlled laboratory animal study.
  
  
  METHODS
  Research laboratory in a university hospital.
  
  
  METHODS
  Forty Sprague-Dawley rats.
  
  
  METHODS
  Sepsis was induced in 32 animals by cecal ligation and puncture. Eight animals served as sham controls. Animals were randomly assigned to five groups: 1) fluid resuscitation (25 ml x kg(-1) x h(-1)), 2) fluid resuscitation plus norepinephrine (0.5 microg x kg(-1) x min(-1)), 3) fluid resuscitation plus levosimendan (0.3 microg x kg(-1) x min(-1)), 4) no treatment and 5) sham control.
  
  
  RESULTS
  Microvascular perfusion was quantitated using sidestream darkfield imaging and microvascular oxygenation (microPO2) was assessed by oxygen-dependent quenching of phosphorescence. Measurements were obtained on the buccal mucosa at baseline and at hourly intervals thereafter. In parallel, cardiac output (CO) was recorded. After induction of sepsis microvascular perfusion and microPO2 were impaired early followed by significant decreases in CO. Although levosimendan and norepinephrine were equally effective in restoring CO, only treatment with levosimendan significantly improved microPO2 after 1 and 2 hours of treatment (9.7 +/- 2.0 vs. 15.1 +/- 2.6 and 16.0 +/- 3.7 mmHg; p < 0.05). Microvascular perfusion was not significantly influenced by any of the treatment strategies.
  
  
  CONCLUSIONS
  In this model, treatment with levosimendan and norepinephrine showed comparable effects in restoring CO and had no significant influence on microvascular perfusion. However, only levosimendan significantly improved microPO2, suggesting that a mechanism relatively independent of macrocirculatory hemodynamics and overall microvascular perfusion might account for these observations.
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany. mfries@ukaachen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
authors.forename: Can
authors.initials: C
authors.lastname: Ince
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.forename: Johannes
authors.initials: J
authors.lastname: Bickenbach
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.forename: Egbert G
authors.initials: EG
authors.lastname: Mik
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009061:Mouth Mucosa / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000503:physiopathology*; D000077464:Simendan; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D019344:Lactic Acid; D000077464:Simendan; D010100:Oxygen; D009638:Norepinephrine