Extrinsic denervation causes adrenergic and cholinergic hypersensitivity in canine jejunum (GE 117:A4668, 1999), which may contribute to motor dysfunction after intestinal transplantation. Little is known about effects of extrinsic denervation on canine ileum. AIM: Investigate adrenergic and cholinergic mechanisms altered by extrinsic denervation in canine ileum.
METHODS: 6 dogs underwent complete extrinsic denervation of the jejunoileum; 6 others had transection/reanastomosis of proximal jejunum and distal ileum to control for celiotomy, anesthesia, and disruption of enteric nervous system. Ileum was studied in tissue chambers at time 0, 2, and 8 wk after operation. Contractile response of 2x10 mm longitudinal muscle strips to acetylcholine (Ach), bethanechol (Be) and norepinephrine (NE) was evaluated with and without the nerve blocker tetrodotoxin (TTX). Area under the contractile curve was measured; estimated dose to achieve 50% and 150% of maximal response (ED50 and ED150) compared to baseline was calculated. ANOVA and paired T-test were used where appropriate.
RESULTS: NE dose-dependently decreased contractile activity. Be and Ach dose-dependently increased contractile activity. Extrinsic denervation did not alter contractile response to NE, Ach or Be (Table). Extrinsic denervation did not alter spontaneous contractile activity at any time point (ANOVA p=0.10). TTX decreased spontaneous contractile activity in all muscle strips at all times (control vs denervated 0 wk: 13.9+1.3 vs 7.9+1.1; 2 wk: 15.9+1.1 vs 10.7+1.2; 8 wk: 15.3+1.7 vs 11.2+1.7 g force 5 min/mg tissue, all p<0.001). TTX had no effect on ED50/150. SUMMARY: Extrinsic denervation does not induce adrenergic or cholinergic hypersensitivity in ileal longitudinal smooth muscle.
CONCLUSION: Response to extrinsic denervation is variable in different regions and muscle layers of the small bowel. Supported by NIH DK39337 and DK07198 (MGS).
Norepinephrine Acetylcholine Bethanechol
Control Ext Den Control Ext Den Control Ext Den
0 wk 6.8±0.1 6.8±0.1 7.6±0.1 7.9±0.2 7.1±0.2 7.1±0.1
2 wk 7.0±0.1 7.1±0.1 7.9±0.1 7.5±0.2 6.9±0.1 6.9±0.1
8wk 6.8±0.1 7.0±0.2 8.1±0.1 7.8±0.4 6.9±0.1 6.9±0.1
-log ED50 (NE) and ED150 (Be & ACh); n=6; x±SEM. Ex Den=extrinsic denervation.