Levosimendan attenuates reperfusion injury in an isolated perfused rat heart model.
OBJECTIVE
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.


METHODS
An in vitro experimental study.


METHODS
Animal laboratory.


METHODS
Isolated perfused rat heart preparation (n = 22).


METHODS
Perfusion with Krebs-Henseleit solution was performed for 30 minutes and then 0.1 micromol/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.


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.
Ozturk
Tulun
T
Department of Anaesthesiology and Reanimation, Celal Bayar University School of Medicine, Manisa, Turkey. ozturktulun@yahoo.com
Gok
Sule
S
Nese
Nalan
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*; D009924:Organ Culture Techniques; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan
D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan