28 Milrinone is Preferred to Levosimendan for Mesenteric Perfusion in Hypoxia-Reoxygenated Newborn Piglets on Dopamine

Abstract

Objectives: To determine the effect on systemic and regional perfusion of adding milrinone or levosimendan to a background infusion of dopamine in newborn piglets following hypoxia-reoxygenation (H-R).Methods: Piglets (1-4d) were instrumented for continuous monitoring of systemic and pulmonary arterial pressures, cardiac output (CI) and common carotid, superior mesenteric and renal arterial flows. Sham piglets (n=6) had no H-R. H-R piglets underwent 2h of hypoxia followed by reoxygenation with 100% (0.5h) and 21% oxygen (3.5h). H-R piglets were blindly randomized (n=6/group) to saline control or dopamine (10 mcg/kg/min) with milrinone (D+M - 50 mcg/kg bolus then 0.5 mcg/kg/min) or levosimendan (D+L - 24 mcg/kg bolus then 0.2 mcg/kg/min). Tissue was collected for biochemical and histological analysis. Data were analyzed using ANOVA.Results: Following 2h of hypoxia, H-R piglets were in cardiogenic shock with depressed CI and hypotension. D+M and D+L treatments increased heart rate, CI and systemic oxygen delivery (all p< 0.05 vs. controls) without significant effects on pressures. Both treatments improved common carotid flow, oxygen delivery and vascular resistance (p< 0.05 vs. controls). D+M additionally improved superior mesenteric flow and oxygen delivery (p< 0.05 vs. controls). No disparate effect was appreciated on renal perfusion. D+M piglets had lower myocardial oxidized-to-total glutathione ratio than controls (p=0.05). No differences were appreciated in plasma lactate, myocardial lactate or histologic indices of H-R injury.Conclusions: In H-R newborn piglets, either milrinone or levosimendan addition to dopamine similarly improves systemic hemodynamics. Milrinone addition, in particular, improves mesenteric perfusion and attenuates myocardial oxidative stress.