title: Intracoronary Levosimendan during Ischemia Prevents Myocardial Apoptosis.
abstract: BACKGROUND
  Levosimendan is a calcium sensitizer that has been shown to prevent myocardial contractile depression in patients post cardiac surgery. This drug exhibits an anti-apoptotic property; however, the underlying mechanism remains elusive. In this report, we characterized the myocardial protective of levosimendan in preventing cardiomyocyte apoptosis and post-operative stunning in an experimental ischemia-reperfusion model.
  
  
  METHODS
  Three groups of pigs (n = 8 per group) were subjected to 40 min of global, cardioplegic ischemia followed by 240 min of reperfusion. Levosimendan (65 μg/kg body weight) was given to pigs by intravenous infusion (L-IV) before ischemia or intracoronary administration during ischemia (L-IC). The Control group did not receive any levosimendan. Echocardiography was used to monitor cardiac function in all groups. Apoptosis levels were assessed from the left ventricle using the terminal transferase mediated dUTP nick end labeling (TUNEL) assay and immunocytochemical detection of Caspase-3.
  
  
  RESULTS
  Pigs after ischemia-reperfusion had a much higher TUNEL%, suggesting that our treatment protocol was effective. Levels of apoptosis were significantly increased in Control pigs that did not receive any levosimendan (0.062 ± 0.044%) relative to those received levosimendan either before (0.02 ± 0.017%, p = 0.03) or during (0.02 ± 0.017%, p = 0.03) the ischemia phase. Longitudinal left ventricular contraction in pigs that received levosimendan before ischemia (0.75 ± 0.12 mm) was significantly higher than those received levosimendan during ischemia (0.53 ± 0.11 mm, p = 0.003) or Control pigs (0.54 ± 0.11 mm, p = 0.01).
  
  
  CONCLUSIONS
  Our results suggested that pigs received levosimendan displayed a markedly improved cell survival post I-R. The effect on cardiac contractility was only significant in our perfusion heart model when levosimendan was delivered intravenously before ischemia.
authors.affiliation: Department of Surgery, Turku University Hospital Turku, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Malmberg
authors.forename: Tommi
authors.initials: T
authors.lastname: Vähäsilta
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Juha W
authors.initials: JW
authors.lastname: Koskenvuo
authors.forename: Jussi P
authors.initials: JP
authors.lastname: Pärkkä
authors.forename: Kari
authors.initials: K
authors.lastname: Leino
authors.forename: Timo
authors.initials: T
authors.lastname: Laitio
authors.forename: Christoffer
authors.initials: C
authors.lastname: Stark
authors.forename: Aira
authors.initials: A
authors.lastname: Heikkilä
authors.forename: Pekka
authors.initials: P
authors.lastname: Saukko
authors.forename: Timo
authors.initials: T
authors.lastname: Savunen