Effects of levosimendan on myocardial ischaemia-reperfusion injury.
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.
Yapici
D
D
University of Mersin, Department of Anaesthesiology and Intensive Care, Mersin, Turkey. davudyapici@yahoo.com
Altunkan
Z
Z
Ozeren
M
M
Bilgin
E
E
Balli
E
E
Tamer
L
L
Doruk
N
N
Birbicer
H
H
Apa
D
D
Oral
U
U
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D008315:Malondialdehyde; D009195:Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase