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The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model

^a Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute, 3-16-1 Asahi-cho, Fuchu-si, Tokyo, 183-0003, Japan
^b Department of Pathology, Sakakibara Heart Institute, Japan

*Corresponding author. Tel.: +81-42-314-3111; fax: +81-42-314-3150.

E-mail address: maando{at}shi.heart.or.jp (M. Ando).

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, PaO₂/FiO₂ 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.

Key Words: Sivelestat sodium; Neutrophil activation; Systemic inflammatory response; Cardiopulmonary bypass