Aktivierung vagaler Hirnstammkerne und Sensibilität extrinsischer afferenter Nervenfasern nach selektiver COX-2-Inhibition während des postoperativen Ileus bei der Maus View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2005

AUTHORS

Mario H. Müller , J. Glatzle , J. Hahn , D. Grundy , K. W. Jauch , M. E. Kreis

ABSTRACT

Introduction: Postoperative ileus entails an inflammatory response in the muscle layer of the small bowel. Intestinal inflammation triggers the release of inflammatory mediators, which have the potential to stimulate intestinal afferents. We aimed to investigate intestinal afferent sensitivity in the mesentery and the brainstem in mice during postoperative ileus with special attention to the role of COX-2. Methods: Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by standardized small bowel manipulation to induce ileus or were left untouched as a sham-treatment group. The animals were killed 24 h later. The brainstem was removed to study Fos immunoreactivity (IR). 3 cm segments of jejunum were placed in Krebs buffer. Extracellular multiunit mesenteric afferent nerve discharge was recorded at baseline and following serosal application of bradykinin (BK 1 μM). Fos IR was quantified in the nucleus of the solitary tract (nTS). Leukocyte infiltration in the intestinal muscularis was determined as an index of post-operative inflammation. Results: The number of leukocytes infiltrating the intestinal muscularis was elevated during ileus compared to controls (39 ± 9 vs. 1.8 ± 1/mm2; P = 0.008, N = 6, mean ± SEM). The selective COX-2 antagonist (5,5-dimethyl-3-(3-fluorophenyl)-4(4-methylsulphonyl) phenyl-2(5H)-furan; DFU, Merck-Frosst) reduced the number of leukocytes in ileus animals to 0.8 ± 0.2/mm2, (N = 5). An increase in the number of Fosositive neurons in the nTS following surgery was observed compared to sham controls (Bregma: − 7.70 mm, 30 ± 9 vs. 6 ± 2; P = 0.01, − 7.32 mm, 107 ± 26 vs. 6 ± 2, P = 0.016, N = 4). In ileus animals this number was unchanged following DFU pre-treatment (Bregma: − 7.70 mm 43 ± 10, n = 5, − 7.32 mm 95 ± 30, n = 5, P < 0.05 vs. controls). Serosal bradykinin (1 μM) was followed by an increase in afferent discharge in ileus segments which peaked at 65 ± 5 imp sec−1 above baseline (N = 10) compared to 37 ± 6 imp sec−1 in sham treated animals (P < 0.05; each N = 10). The afferent response was attenuated following DFU treatment in ileus animals (peak 31 ± 7 imp sec−1, N = 6, P < 0.05). Conclusion: The marked increase of c-fos expression in the nTS during postoperative ileus suggests that vagal afferent pathways were activated, while hypersensitivity to bradykinin, which stimulates predominantly spinal afferents was also observed. DFU reduced this mesenteric afferent sensitivity to bradykinin but not neuronal activation in vagal nuclei in the brainstem. Thus, inflammation induced via the COX-2 pathway may sensitize spinal but not vagal afferents during postoperative ileus. More... »

PAGES

189-191

Book

TITLE

Chirurgisches Forum 2005

ISBN

3-540-24888-9

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/3-540-26560-0_70

DOI

http://dx.doi.org/10.1007/3-540-26560-0_70

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009838088


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