Translational Research Center for GastroIntestinal Disorders (TARGID), Intestinal Neuroimmune Interactions, University of Leuven, Leuven, Belgium.
Department of Abdominal Surgery, University Hospital of Leuven, Leuven, Belgium.
Neurogastroenterol Motil. 2017 Sep;29(9). doi: 10.1111/nmo.13075. Epub 2017 Apr 21.
Electrical stimulation of the cervical vagus nerve (VNS) prevents postoperative ileus (POI) in mice. As this approach requires an additional cervical procedure, we explored the possibility of peroperative abdominal VNS in mice and human.
The effect of cervical and abdominal VNS was studied in a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative ileus was quantified by assessment of intestinal transit of fluorescent dextran expressed as geometric center (GC). Next, the effect of cervical and abdominal VNS on heart rate was determined in eight Landrace pigs to select the optimal electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS-induced cytokine production of whole blood was studied in patients undergoing colorectal surgery.
Similar to cervical VNS, abdominal VNS significantly decreased LPS-induced serum tumor necrosis factor-α (TNFα) levels (abdominal VNS: 366±33 pg/mL vs sham: 822±105 pg/mL; P<.01). In line, in a murine model of POI, abdominal VNS significantly improved intestinal transit (GC: sham 5.1±0.2 vs abdominal VNS: 7.8±0.6; P<.01) and reduced intestinal inflammation (abdominal VNS: 35±7 vs sham: 80±8 myeloperoxidase positive cells/field; P<.05). In pigs, heart rate was reduced by cervical VNS but not by abdominal VNS. In humans, abdominal VNS significantly reduced LPS-induced IL8 and IL6 production by whole blood.
CONCLUSIONS & INFERENCES: Abdominal VNS is feasible and safe in humans and has anti-inflammatory properties. As abdominal VNS improves POI similar to cervical VNS in mice, our data indicate that peroperative abdominal VNS may represent a novel approach to shorten POI in man.
电刺激颈部迷走神经（VNS）可预防术后肠麻痹（POI）在小鼠中。由于这种方法需要额外的颈部手术，我们探索了在小鼠和人类中进行手术期间腹部 VNS 的可能性。
在 POI 和脂多糖（LPS）诱导的败血症的小鼠模型中研究了颈部和腹部 VNS 的效果。通过评估荧光葡聚糖的肠道转运来量化术后肠麻痹，用几何中心（GC）表示。接下来，在 8 头长白猪中确定颈部和腹部 VNS 对心率的影响，以选择人类 VNS 的最佳电极。最后，在接受结直肠手术的患者中研究了假手术或腹部 VNS 对 LPS 诱导的全血细胞因子产生的影响。
与颈部 VNS 相似，腹部 VNS 显著降低 LPS 诱导的血清肿瘤坏死因子-α（TNFα）水平（腹部 VNS：366±33 pg/mL 与假手术：822±105 pg/mL；P<.01）。同样，在 POI 的小鼠模型中，腹部 VNS 显著改善了肠道转运（GC：假手术 5.1±0.2 与腹部 VNS：7.8±0.6；P<.01）并减少了肠道炎症（腹部 VNS：35±7 与假手术：80±8 髓过氧化物酶阳性细胞/场；P<.05）。在猪中，颈部 VNS 降低了心率，但腹部 VNS 没有。在人类中，腹部 VNS 显著降低了 LPS 诱导的全血中 IL8 和 IL6 的产生。
腹部 VNS 在人类中是可行且安全的，具有抗炎作用。由于腹部 VNS 在小鼠中类似于颈部 VNS 改善 POI，我们的数据表明，手术期间腹部 VNS 可能是缩短人类 POI 的一种新方法。
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