Levosimendan Attenuates Reperfusion Injury in an Isolated Perfused Rat Heart Model

ObjectivesThe 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.DesignAn in vitro experimental study.SettingAnimal laboratory.ParticipantsIsolated perfused rat heart preparation (n = 22).InterventionsPerfusion with Krebs-Henseleit solution was performed for 30 minutes and then 0.1 μmol/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 ResultsInfarct 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 placebo-treated hearts (53% ± 3% v 38% ± 3% of baseline, respectively; p = 0.004).ConclusionsLevosimendan 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.