ISSN : 1301-5680
e-ISSN : 2149-8156
Turkish Journal of Thoracic and Cardiovascular Surgery     
Levosimendan attenuates ischemia/reperfusion injury of the heart better than ischemic preconditioning during moderate hypothermia
Davud Yapıcı1, Murat Özeren2, Duygu Apa3, Ebru Ballı4, Lülüfer Tamer5, Şebnem Atıcı1, Nurcan Doruk1, Zeliha Özer1, Uğur Oral1
Medical Faculty of Mersin University, Mersin, Turkey
1Departments of Anaesthesiology and Reanimation, Medical Faculty of Mersin University, Mersin, Turkey
2Departments of Cardiovascular Surgery, Medical Faculty of Mersin University, Mersin, Turkey
3Departments of Pathology, Medical Faculty of Mersin University, Mersin, Turkey
4Departments of Histology, Medical Faculty of Mersin University, Mersin, Turkey
5Departments of Biochemistry, Medical Faculty of Mersin University, Mersin, Turkey
DOI : 10.5606/tgkdc.dergisi.2014.9595
Background: This study aims to demonstrate whether levosimendan offers additive cardioprotection compared with ischemic preconditioning during moderate hypothermia.

Methods: Thirty-six male Wistar rats were selected for the study. Rats’ hearts were rapidly excised after application of ketamine. Aorta was cannulated and infusion of 37 °C Krebs-Henseleit Buffer (KHB) was started to provide heart stabilization for 10 minutes. Then, the isolated hearts were randomly assigned to one of six groups: group 1 (normothermia 37 °C-control), group 2 (hypothermia 28 °C-Control), group 3 (normothermia-ischemic preconditioning), group 4 (hypothermia-ischemic preconditioning), group 5 (normothermialevosimendan), group 6 (hipothermi-levosimendan). Levosimendan was added to KHB solution (24 μg/kg for 10 minutes loading, and 0.1 μg/kg/ minute for maintenance). Data were analyzed by using Kruskal Wallis and Mann-Whitney U test, and p values of <0.05 and <0.008 were accepted significant after using Bonferroni adjustment.

Results: The tissue malondialdehyde (MDA) levels in group 4 were significantly increased compared to group 6 (median range 1.85 vs. 0.70, respectively; p=0.004). Sodium, potassium adenosine triphosphatase (Na+-K+ A TPase) e nzyme a ctivity w as s ignificantly p rotected i n group 6 compared to group 4 (303.6 vs. 209.1, respectively; p=0.004). Group 4 revealed extensive TUNEL-positive cardiomyocytes compared to group 6. Percentage of apoptotic cell staining was 37.5% and 10%, respectively (p=0.004). Electron microscopic evaluation of group 6 showed normal morphological composition characterized by regular arrangement of myofibrils and protected mitochondrial structure and sarcomer in comparison with other groups.

Conclusion: Results of this study showed that separate use of levosimendan and hypothermia provided protective effects on ischemic myocardium. However, pretreatment with levosimendan provided better protection under the moderate hypothermic condition.

Keywords : Heart; hypothermia; ischemic preconditioning; levosimendan
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