Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock

Objective, To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock. Design: Controlled laboratory animal study. Setting. Research laboratory in a university hospital. Subjects: Forty Sprague-Dawley rats. Interventions: 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.kg(-1).h(-1)), 2) fluid resuscitation plus norepinephrine (0.5 mu g.kg(-1).min(-1)), 3) fluid resuscitation plus levosimendan (0.3 mu g.kg(-1).min(-1)), 4) no treatment and 5) sham control. Measurements and Main Results: Microvascular perfusion was quantitated using sidestream darkfield imaging and microvascular oxygenation (mu PO2) 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 mu PO2. 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 mu PO2 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 mu PO2, suggesting that a mechanism relatively independent of macrocirculatory hemodynamics and overall microvascular perfusion might account for these observations.