Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is preserved in a canine model of extrinsic denervation: implications for small bowel transplantation.
BACKGROUND
Small bowel transplantation (SBT) is complicated by changes in graft motility, especially in the early postoperative period. This dysmotility may be related in part to the extrinsic denervation necessitated by the procedure, but specific neurotransmitter response to SBT is incompletely understood. The aim of this study was to evaluate the role of nitric oxide and nonadrenergic, noncholinergic (NANC) enteric neural input in the nonimmunologic etiology of the dysmotility seen after SBT.


METHODS
A technique of jejunoileal extrinsic denervation (without disruption of mesenteric vascular supply) was used as a model of canine jejunoileal autotransplantation to avoid potential confounding factors such as ischemia-reperfusion and postallotransplant immunologic effects. Longitudinal smooth muscle strips from ileum and jejunum were studied with in vitro tissue chamber methodology at 0, 2, and 8 weeks after this experimental model to explore early and late effects of denervation. Effects of exogenous nitric oxide (NO) and electric field stimulation (EFS), which releases native, endogenous enteric neurotransmitters) were evaluated in neurally intact control dogs and those undergoing extrinsic denervation.


RESULTS
Exogenous NO caused a dose-dependent inhibition of spontaneous contractile activity and in some muscle strips a decrease in basal tone in both groups of dogs. These effects were unchanged by neural blockade with tetrodotoxin and preserved after extrinsic denervation. EFS produced inhibition of spontaneous contractile activity in ileum and a complex, inconsistent response in jejunum. The response to EFS in both ileum and jejunum was unchanged after extrinsic denervation.


CONCLUSIONS
Nitric oxide inhibits contractile activity in canine longitudinal muscle of small bowel. Motility changes seen after this large animal model of extrinsic denervation are not caused by changes in NO or NANC neural function. The variability observed between different segments of intestine is important to consider in the context of SBT.
Zyromski
Nicholas J
NJ
Gastroenterology Research Unit and Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Duenes
Judith A
JA
Sarr
Michael G
MG
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003714:Denervation / Q000379:methods*; D004285:Dogs; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000378:metabolism / Q000601:surgery*; D005260:Female; D007082:Ileum / Q000294:innervation / Q000502:physiology / Q000637:transplantation*; D007583:Jejunum / Q000294:innervation / Q000502:physiology / Q000637:transplantation*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology / Q000637:transplantation; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D018674:Adrenergic Antagonists; D018680:Cholinergic Antagonists; D009569:Nitric Oxide