Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is preserved in a canine model of extrinsic denervation: implications for small bowel transplantation.

Inhibition by nitric oxide and nonadrenergic, noncholinergic (NANC) nerves is preserved in a canine model of extrinsic denervation: implications for small bowel transplantation.
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一氧化氮和非肾上腺素能、非胆碱能(NANC)神经的抑制作用保留在犬外源性去神经支配模型中:对小肠移植的影响。

DOI:
10.1016/j.surg.2005.06.029
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发表时间:
2005
期刊:
Surgery.
影响因子:
--
通讯作者:
Sarr,MichaelG
Sarr,MichaelG
中科院分区:
--
文献类型:
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作者:
Zyromski,NicholasJ;Duenes,JudithA;Sarr,MichaelG

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背景:小肠移植(SBT)术后早期移植物运动功能改变较为复杂。这种运动障碍可能部分与手术所必需的外源性失神经有关,但对SBT的特定神经递质反应尚不完全清楚。本研究旨在探讨一氧化氮和非肾上腺素、非胆碱能(NANC)肠神经传入在SBT后运动障碍的非免疫学病因中的作用。方法采用犬自体空回肠外神经去神经(不中断肠系膜血管供应)技术,以避免潜在的混杂因素,如缺血再灌注和同种异体移植后的免疫影响。分别于实验后0、2、8周采用体外组织室法对回肠和空肠纵行肌条进行研究,以探讨去神经支配的早期和晚期效应。观察外源性一氧化氮(NO)和电场刺激(EFS)对神经完整对照犬和外源性失神经犬的作用。结果外源性NO对两组犬的自发收缩活动均有剂量依赖性抑制作用,部分肌条基础张力下降。用河豚毒素阻断神经不影响这些效应,而外源性去神经后保留这些效应。EFS抑制回肠的自发收缩活动,在空肠产生复杂的、不一致的反应。外源性去神经后回肠和空肠对电刺激的反应无明显变化。结论一氧化氮抑制犬小肠纵行肌的收缩活动。在这个外源性去神经的大型动物模型后看到的运动性变化不是由NO或NANC神经功能的变化引起的。在SBT的背景下,观察到不同肠段之间的差异是重要的。
BACKGROUNDSmall 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.METHODSA 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.RESULTSExogenous 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.CONCLUSIONSNitric 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.