title: Effects of levosimendan on myocardial infarct size and hemodynamics in a closed-chest porcine ischemia-reperfusion model.
abstract: BACKGROUND
  Levosimendan is a positive inotropic drug with vasodilator action and proposed myocardioprotective properties. In a canine model, levosimendan increased coronary collateral flow and reduced myocardial infarct size (IS). We investigated the effect of levosimendan on IS and hemodynamics in the closed-chest porcine ischemia-reperfusion model, which is devoid of coronary collaterals.
  
  
  METHODS
  Infusion with levosimendan (0.2 microg/kg/min following a bolus of 24 microg/kg) or saline was initiated 30 min prior to ischemia in anaesthetized pigs (n = 10 in both groups). Balloon occlusion of the left anterior descending coronary artery for 45 min was followed by 2 1/2 h of reperfusion. Hemodynamics were monitored with a Swan-Ganz catheter and a left ventricular pressure micromanometer. Left ventricular systolic and diastolic function was estimated by dP/dt(max) and tau, respectively. Myocardial area at risk (AAR) and IS were assessed in vivo by myocardial perfusion imaging (MPI) and ex vivo by histopathology (fluorescein staining for AAR, tetrazolium staining for IS).
  
  
  RESULTS
  Prior to ischemia, levosimendan improved left ventricular systolic and diastolic function with coincident preload and afterload reduction. Cardiac output increased by 10 +/- 4% (p = 0.04), dP/dt(max) by 15 +/- 5% (p = 0.01). Pulmonary capillary wedge pressure decreased by 18 +/- 3% (p = 0.04), tau by 11 +/- 2% (p = 0.001), and mean arterial pressure by 11 +/- 2% (p < 0.001). A similar trend was observed during ischemia-reperfusion. The ratio of IS/AAR was not reduced by levosimendan compared to saline as evaluated by histopathology (76 +/- 4% vs. 64 +/- 7%, p = 0.12) and by MPI (94 +/- 2% vs. 87 +/- 5%, p = 0.14).
  
  
  CONCLUSIONS
  Levosimendan improves hemodynamics but does not reduce IS in an ischemia-reperfusion model without coronary collaterals.
authors.affiliation: Department of Cardiology B, Research Unit, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, Aarhus, Denmark. martin.busk@ki.au.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Busk
authors.forename: Michael
authors.initials: M
authors.lastname: Maeng
authors.forename: Jens
authors.initials: J
authors.lastname: Kristensen
authors.forename: Jette Scheby
authors.initials: JS
authors.lastname: Berg
authors.forename: Ulrik Markus
authors.initials: UM
authors.lastname: Mortensen
authors.forename: Torsten Toftegaard
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Jens Erik
authors.initials: JE
authors.lastname: Nielsen-Kudsk
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan