Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs

Objective: The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (μHbO₂) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (ḊO₂) and/or oxygen consumption (V̇O₂). We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine. Design: Laboratory experiment. Setting: University animal research laboratory of experimental anesthesiology. Subjects: Chronically instrumented dogs with flow probes for cardiac output measurement. Interventions: Anesthetized, mechanically ventilated dogs (each group n = 6) on different days randomly received levosimendan (10 μg·kg^-1, followed by four infusion steps: 0.125-1.0 μg·kg^-1·min^-1), milrinone (5.0 μg·kg^-1, followed by 1.25-10 μg·kg ^-1·min^-1), or dobutamine (2.5-10.0 μg·kg^-1·min^-1). Since these drugs may modify regional or systemic responses to fluid load, an additional predefined volume challenge was subsequently performed with hydroxyethyl starch 6% (10 mL·kg^-1). Measurements and Main Results: We measured μHbO₂ (reflectance spectrophotometry), ḊO₂, V̇O₂, and systemic hemodynamics. Levosimendan significantly increased μHbO₂ from baseline (∼55% for all groups) to 64 ± 4% and further to 69 ± 2% with volume challenge (mean ± SEM). At the systemic level, levosimendan alone only slightly increased ḊO₂ at a stable V̇O₂. Milrinone elicited similar systemic effects (ḊO₂, V̇O₂, hemodynamics) but failed to increase μHbO₂. Dobutamine, conversely, increased μHbO₂ to a similar extent as levosimendan; however, this was accompanied by marked increases in ḊO₂ and V̇O₂. The gastric mucosa selectivity of these interventions, expressed as slope of the μHbO₂/ḊO₂ relation, was highest for levosimendan (+1.89 and +1.14, without and with volume challenge), compared with milrinone (+0.45 and + 0.47) and dobutamine (+0.48 and + 0.33). Conclusions: Levosimendan is superior to milrinone (no significant regional effects) and dobutamine (marked systemic effects) in increasing gastric mucosal oxygenation selectiveiy (i.e., at only moderately increased ḊO₂ and stable V̇O ₂). If our experimental data apply to the clinical setting, levosimendan may serve as an option to selectively increase gastrointestinal mucosa oxygenation in patients at risk to develop splanchnic ischemia.