Levosimendan Attenuates Reperfusion Injury in an Isolated Perfused Rat Heart Model

• Published in: Journal of cardiothoracic and vascular anesthesia 2010-08, Vol.24 (4), p.624-628
• Main Authors: Ozturk, Tulun, MD, Gok, Sule, MD, Nese, Nalan, MD
• Format: Article
• Language: English
• Subjects: Anesthesia & Perioperative Care; Animals; Apoptosis - drug effects; Apoptosis - physiology; Critical Care; Disease Models, Animal; heart; Hydrazones - therapeutic use; ischemia; isolated preparation; levosimendan; Male; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Organ Culture Techniques; Pyridazines - therapeutic use; Rats; Rats, Wistar; reperfusion injury
• ISSN: 1053-0770; 1532-8422
• DOI: 10.1053/j.jvca.2009.08.003

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 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 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 placebo-treated 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.