Chronic extrinsic denervation after small bowel transplantation in rat jejunum: Effects and adaptation in nitrergic and non-nitrergic neuromuscular inhibitory mechanisms

Background. Extrinsic denervation of the transplanted small bowel could play a substantial role in motor dysfunction of the transplanted gut. We attempted to determine the effect of chronic extrinsic denervation on intestinal contractility. Methods. Jejunal longitudinal muscle strips were obtained from rats 1 week and 8 weeks after (1) syngeneic small bowel transplantation, (2) ischemia/reperfusion, or (3) gut transection/reanastomosis. Nonoperated rats (naive controls) and sham-operated rats (sham controls), 1 week after celiotomy/gut manipulation, served as controls. We evaluated the effects of exogenous nitric oxide, increasing doses of cholinergic and adrenergic agonists, and electrical field stimulation (EFS) in the presence or absence of N^G-monomethyl-L-arginine, methylene blue, tetraethylammonium, or tetrodotoxin. Results. Spontaneous contractile activity (χ ± SEM), when compared with the naive controls (11.3 ± 2.0 g·5 min/mg), was increased in all 4 groups at 1 week (15.9 ± 10 to 19.4 ± 2 g·5 min/mg; P ≤ .03 each) but not at 8 weeks postoperatively. The inhibition of contractile activity by nitric oxide was increased in small bowel transplantation in naive controls at 8 weeks to 80% ± 10% versus 50% ± 7% (P < .02). EFS induced an inhibition of contractile activity that was tetraethylammonium- and tetrodotoxin-sensitive but N^G-monomethyl-L-arginine- and methylene blue-insensitive; the maximal EFS-induced inhibition was increased at 1 week and 8 weeks but only in the small bowel transplantation groups to 103% ± 5% and 95% ± 7%, respectively, versus 72% ± 8% in naive controls (P ≤ .05). Conclusions. Increased inhibition of contractile function after small bowel transplantation lasts at least 8 weeks and is mediated by changes in the enteric neuromuscular unit caused by extrinsic denervation.