title: Intraperitoneally administered, hydrogen-rich physiologic solution protects against postoperative ileus and is associated with reduced nitric oxide production.
abstract: Postoperative ileus, a transient impairment of bowel motility initiated by intestinal inflammation, is common after an abdominal operation and leads to increased hospital stays and costs. Hydrogen has potent anti-inflammatory and antioxidant properties and potential therapeutic value. Solubilized hydrogen may be a portable and practical means of administering therapeutic hydrogen gas. We hypothesized that intraperitoneal administration of hydrogen-rich saline would ameliorate postoperative ileus.
  
  
  
  Ileus was induced via surgical manipulation in mice and rats. The peritoneal cavity was filled with 1.0 mL saline or hydrogen-rich saline (≥1.5-2.0 ppm) before closure of the abdominal incision. Intestinal transit was assessed 24 hours postoperatively. Inflammation was examined by quantitation of neutrophil extravasation and expression of proinflammatory markers. Nitric oxide production was assessed in cultured muscularis propria.
  
  
  
  Surgical manipulation resulted in a marked delay in intestinal transit and was associated with upregulation of proinflammatory cytokines and increased neutrophil extravasation. Bowel dysmotility, induced by surgical manipulation and inflammatory events, was significantly attenuated by intra-abdominal administration of hydrogen-rich saline. Nitric oxide production in the muscle layers of the bowel was inhibited by hydrogen treatment.
  
  
  
  A single intraperitoneal dose of hydrogen-rich saline ameliorates postoperative ileus by inhibiting the inflammatory response and suppressing nitric oxide production.
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Ayana
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Senri Critical Care Medical Center, Saiseikai Senri Hospital, Suita, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kohama
authors.affiliation: Kobe University Graduate School of Health Science, Kobe, Hyogo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Aoyama-Ishikawa
authors.affiliation: Kobe University Graduate School of Health Science, Kobe, Hyogo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Noritomo
authors.initials: N
authors.lastname: Fujisaki
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yumoto
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nosaka
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Naito
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tsukahara
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kotani
authors.affiliation: Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. Electronic address: atsunorinakao@aol.com.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D013505:Digestive System Surgical Procedures / Q000009:adverse effects*; D004195:Disease Models, Animal; D006859:Hydrogen / Q000008:administration & dosage*; D045823:Ileus / Q000209:etiology / Q000517:prevention & control*; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D019999:Pharmaceutical Solutions; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019999:Pharmaceutical Solutions; D009569:Nitric Oxide; D006859:Hydrogen