Skip to main content

Advertisement

Log in

The pig as preclinical model for laparoscopic vagus nerve stimulation

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Cervical vagus nerve stimulation (VNS) prevents manipulation-induced intestinal inflammation and improves intestinal transit in a mouse model of postoperative ileus (POI). Cervical VNS, however, is accompanied by cardiovascular and respiratory side effects. In view of potential clinical application, we therefore evaluated the safety and feasibility of abdominal VNS via laparoscopic approach in a porcine model.

Methods

Six pigs were used in a non-survival study for both cervical and abdominal VNS. Two cardiac pacing electrodes were positioned around the right cervical and posterior abdominal vagus nerve and connected to an external stimulator. VNS was performed using four different settings (5 and 20 Hz, 0.5 and 1 ms pulse width) during 2 min with ECG recording. Laparoscopic VNS was timed and videotaped, and technical difficulties were noted. A validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire was used to evaluate the task and workload.

Results

The procedure was completed in all pigs with 4-port laparoscopic technique. Cervical and abdominal VNS were performed after correct identification and isolation of the nerve, and positioning of the electrodes around the nerve. Median laparoscopic operating time was 16 min (range 8–33 min), and median NASA-TLX was 31 (range 11–74). No major complications were encountered. Reduction of heart rate was between 5.5 and 14 % for cervical VNS and undetectable for abdominal VNS.

Conclusion

In a porcine model, laparoscopic VNS is feasible and safe with cardiac pacing electrodes and may lead to a similar novel approach in humans in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Baig MK, Wexner SD (2004) Postoperative ileus: a review. Dis Colon Rectum 47(4):516–526. doi:10.1007/s10350-003-0067-9

    Article  PubMed  Google Scholar 

  2. Boeckxstaens GE, De Jonge WJ (2010) Neuroimmune mechanisms in postoperative ileus (Gut (2009), 58, (1300-11)). Gut 59(1):140

    Article  CAS  Google Scholar 

  3. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6(8):844–851. doi:10.1038/ni1229

    Article  PubMed  Google Scholar 

  4. Lubbers T, Luyer MD, de Haan JJ, Hadfoune M, Buurman WA, Greve JW (2009) Lipid-rich enteral nutrition reduces postoperative ileus in rats via activation of cholecystokinin-receptors. Ann Surg 249(3):481–487. doi:10.1097/SLA.0b013e318194d187

    Article  PubMed  Google Scholar 

  5. The F, Cailotto C, van der Vliet J, de Jonge WJ, Bennink RJ, Buijs RM, Boeckxstaens GE (2011) Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus. Br J Pharmacol 163(5):1007–1016. doi:10.1111/j.1476-5381.2011.01296.x

    Article  PubMed Central  PubMed  Google Scholar 

  6. The FO, Boeckxstaens GE, Snoek SA, Cash JL, Bennink R, Larosa GJ, van den Wijngaard RM, Greaves DR, de Jonge WJ (2007) Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice. Gastroenterology 133(4):1219–1228. doi:10.1053/j.gastro.2007.07.022

    Article  PubMed  Google Scholar 

  7. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785):458–462. doi:10.1038/35013070

    Article  CAS  PubMed  Google Scholar 

  8. Van Der Zanden EP, Boeckxstaens GE, de Jonge WJ (2009) The vagus nerve as a modulator of intestinal inflammation. Neurogastroenterol Motil : Off J Eur Gastrointest Motil Soc 21(1):6–17. doi:10.1111/j.1365-2982.2008.01252.x

    Article  Google Scholar 

  9. Matteoli G, Boeckxstaens GE (2013) The vagal innervation of the gut and immune homeostasis. Gut 62(8):1214–1222. doi:10.1136/gutjnl-2012-302550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Matteoli G, Gomez-Pinilla PJ, Nemethova A, Di Giovangiulio M, Cailotto C, van Bree SH, Michel K, Tracey KJ, Schemann M, Boesmans W, Vanden Berghe P, Boeckxstaens GE (2014) A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut 63(6):938–948. doi:10.1136/gutjnl-2013-304676

    Article  CAS  PubMed  Google Scholar 

  11. Beekwilder JP, Beems T (2010) Overview of the clinical applications of vagus nerve stimulation. J Clin Neurophysiol : Off Publ Am Electroencephalographic Soc 27(2):130–138. doi:10.1097/WNP.0b013e3181d64d8a

    Article  CAS  Google Scholar 

  12. Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 115(6):1248–1255. doi:10.3171/2011.7.JNS11977

    Article  PubMed  Google Scholar 

  13. Groves DA, Brown VJ (2005) Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 29(3):493–500. doi:10.1016/j.neubiorev.2005.01.004

    Article  PubMed  Google Scholar 

  14. Howland RH (2014) Vagus nerve stimulation. Curr Behav Neurosci Rep 1(2):64–73. doi:10.1007/s40473-014-0010-5

    Article  PubMed Central  PubMed  Google Scholar 

  15. Howland RH (2014) New developments with vagus nerve stimulation therapy. J Psychosoc Nurs Ment Health Serv 52(3):11–14

    PubMed  Google Scholar 

  16. Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C (2013) Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 81(16):1453–1459. doi:10.1212/WNL.0b013e3182a393d1

    Article  PubMed Central  PubMed  Google Scholar 

  17. Kahlow H, Olivecrona M (2013) Complications of vagal nerve stimulation for drug-resistant epilepsy: a single center longitudinal study of 143 patients. Seizure : J Br Epilepsy Assoc 22(10):827–833. doi:10.1016/j.seizure.2013.06.011

    Article  Google Scholar 

  18. Buschman HP, Storm CJ, Duncker DJ, Verdouw PD, van der Aa HE, van der Kemp P (2006) Heart rate control via vagus nerve stimulation. Neuromodulation : J Int Neuromodulation Soc 9(3):214–220. doi:10.1111/j.1525-1403.2006.00062.x

    Article  Google Scholar 

  19. Matheny RG, Shaar CJ (1997) Vagus nerve stimulation as a method to temporarily slow or arrest the heart. Ann Thorac Surg 63(6 Suppl):S28–29

    Article  CAS  PubMed  Google Scholar 

  20. Thompson GW, Levett JM, Miller SM, Hill MR, Meffert WG, Kolata RJ, Clem MF, Murphy DA, Armour JA (1998) Bradycardia induced by intravascular versus direct stimulation of the vagus nerve. Ann Thorac Surg 65(3):637–642

    Article  CAS  PubMed  Google Scholar 

  21. Amark P, Stodberg T, Wallstedt L (2007) Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia 48(5):1023–1024. doi:10.1111/j.1528-1167.2007.01023.x

    Article  PubMed  Google Scholar 

  22. Ardesch JJ, Buschman HP, van der Burgh PH, Wagener-Schimmel LJ, van der Aa HE, Hageman G (2007) Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Clin Neurol Neurosurg 109(10):849–852. doi:10.1016/j.clineuro.2007.07.024

    Article  CAS  PubMed  Google Scholar 

  23. Cristancho P, Cristancho MA, Baltuch GH, Thase ME, O’Reardon JP (2011) Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. J Clin Psychiatry 72(10):1376–1382. doi:10.4088/JCP.09m05888blu

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. M. Wolthuis.

Ethics declarations

This study was approved by the Animal Care and Animal Experiments Committee of KU Leuven (Leuven, Belgium).

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(WMV 54245 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wolthuis, A.M., Stakenborg, N., D’Hoore, A. et al. The pig as preclinical model for laparoscopic vagus nerve stimulation. Int J Colorectal Dis 31, 211–215 (2016). https://doi.org/10.1007/s00384-015-2435-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-015-2435-z

Keywords

Navigation