Document Detail

Milrinone and levosimendan administered after reperfusion improve myocardial stunning in swine.
MedLine Citation:
PMID:  22994851     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: 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.
DESIGN: 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.
Itsuko Shibata; Sungsam Cho; Osamu Yoshitomi; Hiroyuki Ureshino; Takuji Maekawa; Tetsuya Hara; Koji Sumikawa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-10
Journal Detail:
Title:  Scandinavian cardiovascular journal. Supplement     Volume:  47     ISSN:  1651-2510     ISO Abbreviation:  Scand Cardiovasc J Suppl     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-07-02     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  9711058     Medline TA:  Scand Cardiovasc J Suppl     Country:  England    
Other Details:
Languages:  eng     Pagination:  50-7     Citation Subset:  IM    
Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan.
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MeSH Terms
Cardiotonic Agents / administration & dosage*
Disease Models, Animal
Drug Administration Schedule
Hemodynamics / drug effects
Hydrazones / administration & dosage*
Milrinone / administration & dosage*
Myocardial Contraction / drug effects
Myocardial Reperfusion Injury / enzymology,  physiopathology,  prevention & control*
Myocardial Stunning / enzymology,  physiopathology,  prevention & control*
Protein Kinase Inhibitors / pharmacology
Pyridazines / administration & dosage*
Time Factors
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Reg. No./Substance:
0/Cardiotonic Agents; 0/Hydrazones; 0/Protein Kinase Inhibitors; 0/Pyridazines; 349552KRHK/simendan; 78415-72-2/Milrinone; EC Mitogen-Activated Protein Kinases

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