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

AbstractOBJECTIVES:
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 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.
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.
AuthorsTulun Ozturk, Sule Gok, Nalan Nese
JournalJournal of cardiothoracic and vascular anesthesia (J Cardiothorac Vasc Anesth) Vol. 24 Issue 4 Pg. 624-8 (Aug 2010) ISSN: 1532-8422 [Electronic] United States
PMID19875306 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Hydrazones
  • Pyridazines
  • Simendan
Topics
  • Animals
  • Apoptosis (drug effects, physiology)
  • Disease Models, Animal
  • Hydrazones (therapeutic use)
  • Male
  • Myocardial Reperfusion Injury (pathology, prevention & control)
  • Organ Culture Techniques
  • Pyridazines (therapeutic use)
  • Rats
  • Rats, Wistar
  • Simendan

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