Levosimendan Attenuates Reperfusion Injury in an Isolated Perfused Rat Heart Model
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Objectives: The aim of this study was to investigate the effect of levosimendan on apoptosis and infarct size when administered before ischemia in an isolated rat heart model. Design: An in vitro experimental study. Setting: Animal laboratory. Participants: Isolated perfused rat heart preparation (n = 22). Interventions: Perfusion with Krebs-Henseleit solution was performed for 30 minutes and then 0.1 mu mol/L of levosimendan was added to the perfusion fluid for 10 minutes before global ischemia; the control hearts received no levosimendan. Hearts underwent global ischemia for 30 minutes and then were reperfused for 30 minutes before specimens were obtained for testing. Measurements and Main Results: Infarct sizes were measured at the end of the reperfusion period and expressed as a percentage of the area at risk. Myocardial apoptosis was detected by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) method. Bcl-2 expression was determined to detect antiapoptotic activity. Infarct size was significantly less in the levosimendan group (26% +/- 3% v 40% +/- 4%, respectively; p = 0.009). Levosimendan significantly reduced the proportion of TUNEL-positive cardiomyocytes (3 1 v 20 4, respectively; p < 0.001) and increased Bcl-2 expression compared with control hearts (44% +/- 3% v 31% +/- 3%, respectively; p = 0.01). Recovery of left ventricular developed pressure 30 minutes after reperfusion in ischemic hearts pretreated with levosimendan was significantly better than that of placebotreated hearts (53% +/- 3% v 38% +/- 3% of baseline, respectively; p = 0.004). Conclusions: Levosimendan has a cardioprotective effect when administered before ischemia in ischemia-reperfusion injury. This effect may be useful in elective cardiac surgery for protecting myocytes from ischemia-reperfusion induced apoptosis. (C) 2010 Elsevier Inc. All rights reserved.