Laparoscopic surgery and the parasympathetic nervous system

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.

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.

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.

CO₂ pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.