title: Milrinone and levosimendan administered after reperfusion improve myocardial stunning in swine.
abstract: OBJECTIVE
  We assessed the effect of milrinone application timing after reperfusion against myocardial stunning as compared with levosimendan in swine. Furthermore, we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the milrinone-induced cardioprotection.
  
  
  METHODS
  All swine were subjected to 12-minutes ischemia followed by 90-minutes reperfusion to generate stunned myocardium. Milrinone or levosimendan was administered intravenously either for 20 minutes starting just after reperfusion or for 70 minutes starting 20 minutes after reperfusion. In another group, SB203580, a selective p38 MAPK inhibitor, was administered with and without milrinone. Regional myocardial contractility was assessed by percent segment shortening (%SS).
  
  
  RESULTS
  Milrinone starting just after reperfusion, but not starting 20 minutes after reperfusion, improved %SS at 30, 60, and 90 minutes after reperfusion compared with that in the control group. SB203580 abolished the beneficial effect of milrinone. On the other hand, levosimendan starting 20 minutes after reperfusion, but not for 20 minutes starting just after reperfusion, improved %SS at 60 and 90 minutes after reperfusion.
  
  
  CONCLUSIONS
  Milrinone should be administered just after reperfusion to protect myocardial stunning through p38 MAPK, whereas levosimendan improvement of contractile function could be mainly dependent on its positive inotropic effect.
authors.affiliation: Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Shibata
authors.forename: Sungsam
authors.initials: S
authors.lastname: Cho
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshitomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ureshino
authors.forename: Takuji
authors.initials: T
authors.lastname: Maekawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.forename: Koji
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000008:administration & dosage*; D008297:Male; D020105:Milrinone / Q000008:administration & dosage*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000008:administration & dosage*; D000077464:Simendan; D013552:Swine; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D000077464:Simendan; D048051:p38 Mitogen-Activated Protein Kinases; D020105:Milrinone