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

¹ Sakakibara Heart Institute, Tokyo, Japan

^* To whom correspondence should be addressed. E-mail: maando{at}shi.heart.or.jp.

	Abstract

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. Keywords: Sivelestat sodium; Neutrophil activation; Systemic inflammatory response; Cardiopulmonary bypass