title: Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation.
abstract: BACKGROUND
  Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates.
  
  
  METHODS
  Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 μg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared.
  
  
  RESULTS
  At 0.1 and 0.2 μg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 μg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 μg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels.
  
  
  CONCLUSIONS
  In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.
authors: Department of Pediatrics, University of Alberta, Edmonton, Alta., Canada.
authors: J
authors: J
authors: Esch
authors: C
authors: C
authors: Joynt
authors: N
authors: N
authors: Manouchehri
authors: T F
authors: TF
authors: Lee
authors: Y-Q
authors: YQ
authors: Li
authors: D
authors: D
authors: Bigam
authors: M
authors: M
authors: Vento
authors: P-Y
authors: PY
authors: Cheung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D006835:Hydrazones / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage*; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013552:Swine / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D010100:Oxygen