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 pla y a substantial role in motor dysfunction of the transplanted gut. We attem pted 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/r eperfusion, or (3) gut transection/reanastomosis. Nonoperated rats (naive c ontrols) and sham-operated rats (sham controls), 1 week after celiotomy/gut manipulation, served as controls. We evaluated the effects of exogenous ni tric oxide, increasing doses of cholinergic and adrenergic agonists, and el ectrical field stimulation (EFS) in the presence or absence of N-G-monometh yl-L-arginine, methylene blue, tetraethylammonium, or tetrodotoxin. Results. Spontaneous contractile activity (<(<chi>)over bar> +/- 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 less tha n or equal to .03 each) but not at 8 weeks postoperatively. The inhibition of contractile activity by nitric oxide was increased in small bowel transp lantation in name controls at 8 weeks to 80 % +/- 10 % versus 50 % +/- 7 % (P < .02). EFS induced an inhibition of contractile activity that was tetra ethylammonium- and tetrodotoxin-sensitive but N-G-monomethyl-L-arginine- an d methylene blue-insensitive; the maximal EFS-induced inhibition was increa sed at 1 week and 8 weeks but only in the small bowel transplantation group s to 103 % +/- 5 % and 95 % +/- 7 %, respectively, versus 72 % +/- 8 % in n aive controls (P <less than or equal to> .05). Conclusions. Increased inhibition of contractile function after small bowel transplantation lasts at least 8 weeks and is mediated by changes in the e nteric neuromuscular unit caused by extrinsic denervation.