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Effects of levosimendan on myocardial ischaemia–reperfusion injury

Published online by Cambridge University Press:  01 January 2008

D. Yapici ,
Z. Altunkan ,
M. Ozeren ,
E. Bilgin ,
E. Balli ,
L. Tamer ,
N. Doruk ,
H. Birbicer ,
D. Apa  and
U. Oral
D. Yapici*
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
Z. Altunkan
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
M. Ozeren
Affiliation:
University of Mersin, Department of Cardiovascular Surgery, Mersin, Turkey
E. Bilgin
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
E. Balli
Affiliation:
University of Mersin, Department of Histology, Mersin, Turkey
L. Tamer
Affiliation:
University of Mersin, Department of Biochemistry, Mersin, Turkey
N. Doruk
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
H. Birbicer
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
D. Apa
Affiliation:
University of Mersin, Department of Pathology, Mersin, Turkey
U. Oral
Affiliation:
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey
*
Correspondence to: Davud Yapici, Department of Anaesthesiology and Intensive Care, Mersin University Medical Faculty, Zeytinlibahce C., 33079 Mersin, Turkey. E-mail: [email protected]; Tel: +90 324 3374300; Fax: +90 324 3374305
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Summary

Background and objective

Levosimendan has a cardioprotective action by inducing coronary vasodilatation and preconditioning by opening KATP channels. The aim of this study was to determine whether levosimendan enhances myocardial damage during hypothermic ischaemia and reperfusion in isolated rat hearts.

Methods

Twenty-one male Wistar rats were divided into three groups. After surgical preparation, coronary circulation was started by retrograde aortic perfusion using Krebs–Henseleit buffer solution and lasted 15 min. After perfusion Group 1 (control; n = 7) received no further treatment. In Group 2 (non-treated; n = 7), hearts were arrested with cold cardioplegic solution after perfusion and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. In Group 3 (levosimendan treated; n = 7), levosimendan was added to the buffer solution during perfusion and the hearts were arrested with cold cardioplegic solution and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. At the end of the reperfusion period, the hearts were prepared for biochemical assays and for histological analysis.

Results

Tissue malondialdehyde levels were significantly lower in the levosimendan-treated group than in the non-treated group (P = 0.019). The tissue Na+–K+ ATPase activity was significantly decreased in the non-treated group than in the levosimendan-treated group (P = 0.027). Tissue myeloperoxidase (MPO) enzyme activity was significantly higher in the non-treated group than in the levosimendan-treated group (P = 0.004). Electron microscopic examination of the hearts showed cardiomyocytic degeneration at the myofibril, mitochondria and sarcoplasmic reticulum in both non-treated and levosimendan-treated groups. The severity of these findings was more extensive in the non-treated group.

Conclusions

Treatment with levosimendan provided better cardioprotection with cold cardioplegic arrest followed by global hypothermic ischaemia in isolated rat hearts.

Keywords

HEARTDRUG, levosimendanISCHEMIC PRECONDITIONING, hypothermic, cardioplegicRAT
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 1 , January 2008 , pp. 8 - 14
Copyright
Copyright © European Society of Anaesthesiology 2007

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