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Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine.

AbstractPURPOSE:
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.
AuthorsDaiji Akiyama, Tetsuya Hara, Osamu Yoshitomi, Takuji Maekawa, Sungsam Cho, Koji Sumikawa
JournalJournal of anesthesia (J Anesth) Vol. 24 Issue 4 Pg. 575-81 (Aug 2010) ISSN: 1438-8359 [Electronic] Japan
PMID20464430 (Publication Type: Journal Article)
Chemical References
  • Interleukin-6
  • Proteinase Inhibitory Proteins, Secretory
  • Sulfonamides
  • sivelestat
  • Glycine
Topics
  • 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

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