Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model

Abstract

Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n= 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n= 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 microg/kg followed by an infusion of 0.67 microg/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia.