Document Detail


Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine.
MedLine Citation:
PMID:  20464430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: It seems controversial whether or not neutrophil elastase inhibitors are effective in attenuating myocardial ischemia/reperfusion injury. We thus investigated possible protective effects of sivelestat, a neutrophil elastase inhibitor, against myocardial stunning i.e., prolonged myocardial dysfunction following a brief episode of ischemia.
METHODS: Swine were divided into control group (group C), low-dose sivelestat group (group L), and high-dose sivelestat group (group H) (n = 7 for each group). All the swine were subjected to myocardial ischemia through ligation of the left anterior descending (LAD) coronary artery for 12-min, followed by 90-min reperfusion. Sivelestat was infused intracoronally at concentrations of 6 and 60 mg/ml throughout the reperfusion period in groups L and H, respectively, while saline was infused in the group C. Heart rate (HR), left ventricular developed pressure (LVdP), maximum rate of LVdP (LVdP/dt (max)), LV end-diastolic pressure (LVEDP), percentage of segment shortening (%SS, an index of regional myocardial contractility), and coronary venous interleukin-6 concentration in the LAD perfusion area were measured before ischemic induction and during reperfusion.
RESULTS: The ischemia/reperfusion insult did not cause any significant changes in HR, LVdP, LVdP/dt (max), and LVEDP in all groups. However, it significantly reduced %SS in the LAD perfusion area and increased the interleukin-6 concentration in group C. Those changes in %SS and the interleukin-6 concentration were both greatly attenuated, but not prevented, in groups L and H.
CONCLUSION: Sivelestat presumably attenuates myocardial contractile dysfunction due to myocardial stunning by inhibiting neutrophil-derived elastase, thereby suppressing the production of interleukin-6 in activated neutrophils.
Authors:
Daiji Akiyama; Tetsuya Hara; Osamu Yoshitomi; Takuji Maekawa; Sungsam Cho; Koji Sumikawa
Publication Detail:
Type:  Journal Article     Date:  2010-05-13
Journal Detail:
Title:  Journal of anesthesia     Volume:  24     ISSN:  1438-8359     ISO Abbreviation:  J Anesth     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-05     Completed Date:  2010-12-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8905667     Medline TA:  J Anesth     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  575-81     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Circulation / drug effects
Female
Glycine / analogs & derivatives*,  therapeutic use
Interleukin-6 / biosynthesis
Male
Myocardial Ischemia / drug therapy*
Myocardial Stunning / prevention & control*
Proteinase Inhibitory Proteins, Secretory / therapeutic use*
Sulfonamides / therapeutic use*
Swine
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Proteinase Inhibitory Proteins, Secretory; 0/Sulfonamides; 127373-66-4/ONO 5046; 56-40-6/Glycine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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