Protective effect of sivelestat sodium hydrate (ONO-5046) on ischemic spinal cord injury.
Prevention of paraplegia remains an important issue in repair of descending thoracic and thoracoabdominal aneurysms. Therefore, we investigated the protective effect of sivelestat sodium hydrate (ONO-5046) on ischemia-induced spinal cord damage in a rabbit model. Twenty New Zealand white rabbits were divided into two equal groups; ONO-5046 (1.6 mg/kg)+isotonic NaCl (30 ml) was administered selectively to the spinal cord via the lumbar arteries for the first 3 min during 30 min of infra-renal aorta clamping in the experimental group (group E), whereas NaCl was given alone in the control group (group C). Motor function of the lower limbs was assessed two days later by Tarlov criteria. The number of intact motor neurons in the anterior segment of the cord (L5 level) was counted after hematoxylin-eosin staining and the number of apoptotic motor neurons after TUNEL staining. Motor function of the lower limbs in group E was significantly better (P=0.003) than that in group C. The number of intact motor neurons was greater and of apoptotic motor neurons was less in group E than C. Selective infusion of sivelestat sodium hydrate directly into the spinal cord via the lumbar arteries significantly attenuated functional and morphological ischemia-induced spinal cord injury.
Iwamoto
Satoshi
S
Department of Thoracic and Cardiovascular Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Kagoshima, Japan. surgery2kadai@yahoo.co.jp
Higashi
Akihiro
A
Ueno
Tetsuya
T
Goto
Masamichi
M
Iguro
Yoshifumi
Y
Sakata
Ryuzo
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010264:Paraplegia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D018696:Neuroprotective Agents; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine