Effects of levosimendan on myocardial infarct size and hemodynamics in a closed-chest porcine ischemia-reperfusion model

Levosimendan is a positive inotropic drug with vasodilator action and proposed myocardioprotective properties. In a canine model, levosimendan increased coronary collateral flow and reduced myocardial infarct size (IS). We investigated the effect of levosimendan on IS and hemodynamics in the closed-chest porcine ischemia-reperfusion model, which is devoid of coronary collaterals. Infusion with levosimendan (0.2 mu g/kg/min following a bolus of 24 mu g/kg) or saline was initiated 30 min prior to ischemia in anaesthetized pigs (n=10 in both groups). Balloon occlusion of the left anterior descending coronary artery for 45 min was followed by 2 1/2 h of reperfusion. Hemodynamics were monitored with a Swan-Ganz catheter and a left ventricular pressure micromanometer. Left ventricular systolic and diastolic function was estimated by dP/dt(max) and tau, respectively. Myocardial area at risk (AAR) and IS were assessed in vivo by myocardial perfusion imaging (MPI) and ex vivo by histopathology (fluorescein staining for AAR, tetrazolium staining for IS). Prior to ischemia, levosimendan improved left ventricular systolic and diastolic function with coincident preload and afterload reduction. Cardiac output increased by 10 +/- 4% (p=0.04), dP/dt(max) by 15 +/- 5% (p=0.01). Pulmonary capillary wedge pressure decreased by 18 +/- 3% (p=0.04), tau by 11 +/- 2% (p=0.001), and mean arterial pressure by 11 +/- 2% (p < 0.001). A similar trend was observed during ischemia-reperfusion. The ratio of IS/AAR was not reduced by levosimendan compared to saline as evaluated by histopathology (76 +/- 4% vs. 64 +/- 7%, p=0.12) and by MPI (94 +/- 2% vs. 87 +/- 5%, p=0.14). Levosimendan improves hemodynamics but does not reduce IS in an ischemia-reperfusion model without coronary collaterals.