title: Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.
abstract: BACKGROUND
  Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia.
  
  
  METHODS
  Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery.
  
  
  RESULTS
  During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable.
  
  
  CONCLUSIONS
  These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Örebro University Hospital, Örebro, Sweden. birger.axelsson@orebroll.se
authors.forename: B
authors.initials: B
authors.lastname: Axelsson
authors.forename: G
authors.initials: G
authors.lastname: Johansson
authors.forename: P
authors.initials: P
authors.lastname: Abrahamsson
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: H
authors.initials: H
authors.lastname: Tydén
authors.forename: P
authors.initials: P
authors.lastname: Wouters
authors.forename: M
authors.initials: M
authors.lastname: Haney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage; D006019:Glycolysis / Q000187:drug effects; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D017136:Ion Transport / Q000187:drug effects*; D017551:Microdialysis; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D017202:Myocardial Ischemia / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011292:Premedication; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D000077464:Simendan; D034421:Sus scrofa; D013552:Swine
chemical_list: D002132:Calcium Radioisotopes; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D005947:Glucose; D020105:Milrinone; D002118:Calcium