Motonari Ri1, Kazuhiko Fukatsu, Taiki Miyakuni, Masashi Yanagawa, Satoshi Murakoshi, Hiroshi Yasuhara, Yasuyuki Seto. 1. *Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan †Department of Surgical Center, The University of Tokyo, Tokyo, Japan ‡Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan §Department of Laboratory of Veterinary Surgery, The University of Tokyo, Tokyo, Japan.
Abstract
BACKGROUND: How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear. MATERIALS AND METHODS: Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured. RESULTS: Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group. CONCLUSIONS: Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.
BACKGROUND: How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear. MATERIALS AND METHODS: Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured. RESULTS: Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group. CONCLUSIONS: Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.