Abstract
Background
Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway.
Methods
In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay.
Results
Serum tumor necrosis factor-α (TNF-α) levels were consistently suppressed among the saline–CO2 pneumoperitoneum groups compared to saline–LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-α levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-α production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-α production in all four experiments.
Conclusion
CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.





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Acknowledgments
This work was supported by National Institutes of Health grant R01-GM062899-02. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of Defense.
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Paper presented at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Fort Lauderdale, Florida, USA, April 2005
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Fuentes, J.M., Hanly, E.J., Aurora, A.R. et al. Laparoscopic surgery and the parasympathetic nervous system. Surg Endosc 20, 1225–1232 (2006). https://doi.org/10.1007/s00464-005-0280-9
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DOI: https://doi.org/10.1007/s00464-005-0280-9