title: Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?
abstract: BACKGROUND
  Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury.
  
  
  METHODS
  Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured.
  
  
  RESULTS
  In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment.
  
  
  CONCLUSIONS
  Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Onody
authors.forename: Rita
authors.initials: R
authors.lastname: Stangl
authors.forename: Andras
authors.initials: A
authors.lastname: Fulop
authors.forename: Oliver
authors.initials: O
authors.lastname: Rosero
authors.forename: David
authors.initials: D
authors.lastname: Garbaisz
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Turoczi
authors.forename: Gabor
authors.initials: G
authors.lastname: Lotz
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Balla
authors.forename: Viktor
authors.initials: V
authors.lastname: Hegedus
authors.forename: Laszlo
authors.initials: L
authors.lastname: Harsanyi
authors.forename: Attila
authors.initials: A
authors.lastname: Szijarto
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006835:Hydrazones / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D000077464:Simendan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D050884:HSP72 Heat-Shock Proteins; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D011065:Poly(ADP-ribose) Polymerases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
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