N Stakenborg1, A M Wolthuis2, P J Gomez-Pinilla1, G Farro1, M Di Giovangiulio1, G Bosmans1, E Labeeuw1, M Verhaegen3, I Depoortere4, A D'Hoore2, G Matteoli5, G E Boeckxstaens1. 1. Translational Research Center for GastroIntestinal Disorders (TARGID), Intestinal Neuroimmune Interactions, University of Leuven, Leuven, Belgium. 2. Department of Abdominal Surgery, University Hospital of Leuven, Leuven, Belgium. 3. Department of Anesthesiology, University Hospital of Leuven, Leuven, Belgium. 4. Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Leuven, Belgium. 5. Translational Research Center for GastroIntestinal Disorders (TARGID), Laboratory of Mucosal Immunology, University of Leuven, Leuven, Belgium.
Abstract
BACKGROUND:Electrical stimulation of the cervical vagus nerve (VNS) prevents postoperative ileus (POI) in mice. As this approach requires an additional cervical procedure, we explored the possibility of peroperative abdominal VNS in mice and human. METHODS: The effect of cervical and abdominal VNS was studied in a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative ileus was quantified by assessment of intestinal transit of fluorescent dextran expressed as geometric center (GC). Next, the effect of cervical and abdominal VNS on heart rate was determined in eight Landrace pigs to select the optimal electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS-induced cytokine production of whole blood was studied in patients undergoing colorectal surgery. KEY RESULTS: Similar to cervical VNS, abdominal VNS significantly decreased LPS-induced serum tumor necrosis factor-α (TNFα) levels (abdominal VNS: 366±33 pg/mL vs sham: 822±105 pg/mL; P<.01). In line, in a murine model of POI, abdominal VNS significantly improved intestinal transit (GC: sham 5.1±0.2 vs abdominal VNS: 7.8±0.6; P<.01) and reduced intestinal inflammation (abdominal VNS: 35±7 vs sham: 80±8 myeloperoxidase positive cells/field; P<.05). In pigs, heart rate was reduced by cervical VNS but not by abdominal VNS. In humans, abdominal VNS significantly reduced LPS-induced IL8 and IL6 production by whole blood. CONCLUSIONS & INFERENCES: Abdominal VNS is feasible and safe in humans and has anti-inflammatory properties. As abdominal VNS improves POI similar to cervical VNS in mice, our data indicate that peroperative abdominal VNS may represent a novel approach to shorten POI in man.
RCT Entities:
BACKGROUND: Electrical stimulation of the cervical vagus nerve (VNS) prevents postoperative ileus (POI) in mice. As this approach requires an additional cervical procedure, we explored the possibility of peroperative abdominal VNS in mice and human. METHODS: The effect of cervical and abdominal VNS was studied in a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative ileus was quantified by assessment of intestinal transit of fluorescent dextran expressed as geometric center (GC). Next, the effect of cervical and abdominal VNS on heart rate was determined in eight Landrace pigs to select the optimal electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS-induced cytokine production of whole blood was studied in patients undergoing colorectal surgery. KEY RESULTS: Similar to cervical VNS, abdominal VNS significantly decreased LPS-induced serum tumor necrosis factor-α (TNFα) levels (abdominal VNS: 366±33 pg/mL vs sham: 822±105 pg/mL; P<.01). In line, in a murine model of POI, abdominal VNS significantly improved intestinal transit (GC: sham 5.1±0.2 vs abdominal VNS: 7.8±0.6; P<.01) and reduced intestinal inflammation (abdominal VNS: 35±7 vs sham: 80±8 myeloperoxidase positive cells/field; P<.05). In pigs, heart rate was reduced by cervical VNS but not by abdominal VNS. In humans, abdominal VNS significantly reduced LPS-induced IL8 and IL6 production by whole blood. CONCLUSIONS & INFERENCES: Abdominal VNS is feasible and safe in humans and has anti-inflammatory properties. As abdominal VNS improves POI similar to cervical VNS in mice, our data indicate that peroperative abdominal VNS may represent a novel approach to shorten POI in man.
Authors: Gun-Soo Hong; Bogdan Pintea; Philipp Lingohr; Christoph Coch; Thomas Randau; Nico Schaefer; Sven Wehner; Joerg C Kalff; Dimitrios Pantelis Journal: Int J Colorectal Dis Date: 2018-12-05 Impact factor: 2.571
Authors: Kun-Han Lu; Jiayue Cao; Robert Phillips; Terry L Powley; Zhongming Liu Journal: Neurogastroenterol Motil Date: 2020-04-15 Impact factor: 3.598
Authors: Elisa Meroni; Nathalie Stakenborg; Pedro J Gomez-Pinilla; Michelle Stakenborg; Javier Aguilera-Lizarraga; Morgane Florens; Marcello Delfini; Veronica de Simone; Gert De Hertogh; Gera Goverse; Gianluca Matteoli; Guy E Boeckxstaens Journal: Front Med (Lausanne) Date: 2021-07-07