Ayana Okamoto1, Keisuke Kohama2, Michiko Aoyama-Ishikawa3, Hayato Yamashita3, Noritomo Fujisaki1, Taihei Yamada1, Tetsuya Yumoto4, Nobuyuki Nosaka4, Hiromichi Naito4, Kohei Tsukahara4, Atsuyoshi Iida4, Keiji Sato4, Joji Kotani1, Atsunori Nakao5. 1. Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. 2. 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. 3. Kobe University Graduate School of Health Science, Kobe, Hyogo, Japan. 4. Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 5. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: A single intraperitoneal dose of hydrogen-rich saline ameliorates postoperative ileus by inhibiting the inflammatory response and suppressing nitric oxide production.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: A single intraperitoneal dose of hydrogen-rich saline ameliorates postoperative ileus by inhibiting the inflammatory response and suppressing nitric oxide production.