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Occult injury in the residual lung after pneumonectomy in mice

^a Department of Surgery, Saiseikai Utsunomiya Hospital, Tochigi, Japan
^b Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
^c Department of Medicine, Keio University School of Medicine, Tokyo, Japan
^d Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
^e Department of Veterinary Biochemistry, Rakuno Gakuen University, Hokkaido, Japan

Corresponding author. Tel.: +81-3-5363-3806; fax: +81-3-5363-3499.

E-mail address: kohno{at}1993.jukuin.keio.ac.jp (M. Kohno).

Objectives: We aimed to determine the acute phase impact of pneumonectomy with respect to injury in the remaining lung using a murine model, and to investigate the profiles of inflammatory mediators including high mobility group box 1 protein (HMGB1) following surgery and administration of low dose intratracheal lipopolysaccharide. Methods: Mice received left pneumonectomy with intratracheal administration of either saline or lipopolysaccharide. Lung permeability index, lung wet-to-dry weight ratio, pathological findings, HMGB1 levels in bronchoalveolar lavage fluid (BALF) and plasma, and cytokine profiles in BALF were assessed 24 h after surgery. Results: Index of capillary permeability, lung water content, and neutrophil and macrophage counts in BALF were significantly increased by pneumonectomy. These parameters were highest in the mice with pneumonectomy with intratracheal administration of lipopolysaccharide. On lung pathology, neutrophil infiltration was prominent in the residual lung after pneumonectomy. HMGB1 levels were significantly higher in both BALF and plasma in the mice with pneumonectomy, and were highest in those with pneumonectomy and intratracheal administration of lipopolysaccharide. Pro-inflammatory cytokine levels including interferon- significantly increased in BALF in the mice with pneumonectomy. Conclusions: It was suggested that pneumonectomy itself may cause occult lung injury in the acute phase (24 h) of post-surgery which could be enhanced by inflammatory stimulus, such as bacterial component, leading to significant lung injury. HMGB1 might be involved in the pathogenesis of the occult lung injury.

Key Words: Pneumonectomy; Lung injury; Endotoxin; HMGB1