The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model.
Cardiopulmonary bypass may cause acute lung injury and can seriously affect postoperative outcome, especially in younger patients. A synthesized neutrophil elastase inhibitor, sivelestat sodium, may be most effective when used during cardiopulmonary bypass. After anesthesia induction, sivelestat (2 mg/kg/h) was given to the SS group (n=7), and 0.9% saline solution to the placebo group (n=7). Piglets were placed on hypothermic cardiopulmonary bypass and subjected to myocardial ischemia (2 h) induced by cold crystalloid cardioplegia. At 24 h after surgery, PaO(2)/FiO(2) ratio and alveolar-arterial oxygen difference were significantly better in the SS group (379.1+/-93.9 mmHg and 250.5+/-89.3 mmHg) than the placebo group (232.4+/-105.3 mmHg, and 378.3+/-90.8 mmHg, P<0.05). Interleukin-8 level in the epithelial lining fluid was above the lowest standard in 6 out of 7 (4.5, 12.9, 24.6, 27.7, 37.7, and 159.8; mean=44.5+/-57.6 g/l) in the placebo group, and in 2 out of 7 (36.1 and 67.8 g/l) in the SS group (P<0.05). The median histological score of acute lung injury in the harvested lung was 3 (2-5) in the placebo group and 1 (1-5) in the SS group (P<0.05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model.
Ando
Makoto
M
Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute,Fuchu-si, Tokyo, Japan. maando@shi.heart.or.jp
Murai
Tatsuya
T
Takahashi
Yukihiro
Y
D000818:Animals; D000831:Animals, Newborn; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine