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


CONCLUSIONS
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.
Akiyama
Daiji
D
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hara
Tetsuya
T
Yoshitomi
Osamu
O
Maekawa
Takuji
T
Cho
Sungsam
S
Sumikawa
Koji
K
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D017682:Myocardial Stunning / Q000517:prevention & control*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013552:Swine
D015850:Interleukin-6; D053491:Proteinase Inhibitory Proteins, Secretory; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine
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