Back to Annual Meeting Program

Background:
The role of α-receptors in control of intestinal motility is poorly understood. We aimed to study the mechanism of action of α₁- and α₂-agonists and to investigate changes in α-adrenergic neurotransmission potentially participating in pathophysiology of POI.
Methods:
Circular, jejunal muscle strips (n=8/rat) were obtained from male Sprague Dawley rats (n=6/group). Groups: Naïve controls (NC), sham controls 12h and 3d after laparotomy to study combined effects of anesthesia and laparotomy (SC12h, SC3d), and rats 12h and 3d after laparotomy and small bowel manipulation (P12h, P3d) to induce POI. Dose-dependent effects of α₁-agonist phenylephrine (10^-8-10^-5M) and α₂-agonist clonidine (3x10^-8-3x10^-5M) without and with TTX (blocking enteric nerves; 10^-6M), L-NIL (blocking inducible nitric oxide-synthase; 3x10^-5M) and nimesulide (blocking cyclooxygenase-2; 10^-5M), or α-receptor antagonist phentolamine (10^-5M) were studied. Intestinal transit was studied by charcoal gavage ([%] small bowel passed by marker). Histology in whole mounts was performed for myeloperoxidase positive cells (MPO), macrophages, and mastcells (cells/mm²). Data: mean±SEM.
Results:
Phenylephrine and clonidine caused dose-dependent inhibition in all groups (p<0.05). Phenylephrine-induced inhibition was increased only in SC3d (p<0.05 vs NC). TTX reduced phenylephrine-induced inhibition in NC, P3d, and SC3d (all p<0.05 vs without TTX), while L-NIL and nimesulide had no effect on phenylephrine-induced inhibition (p=NS vs without L-NIL and nimesulide). Clonidine-induced inhibition was reduced in P3d and SC12h (p<0.05 vs NC). TTX reduced clonidine-induced inhibition in NC while it increased the clonidine-effect in P3d (both p<0.05 vs without TTX). L-NIL and nimesulide reduced clonidine-induced inhibition in P12h, SC12h, and SC3d (all p<0.05 vs without L-NIL and nimesulide). Phentolamine prevented phenylephrine- and clonidine-induced inhibition in all groups (all p<0.05). Intestinal transit was delayed only in P12h (P12h 28±3; NC 54±2%; p<0.05 vs NC). MPO positive cells and mast cells were increased in P12h and P3d, but not in sham controls (MPO: NC 12±2; P12h 908±125; P3d 828±84; mastcells: NC 19±4; P12h 639±174; P3d 1137±225; all p<0.05 vs NC). Macrophages were elevated in only P3d (NC 369±30; P3d 1274±237; p<0.05 vs NC).
Conclusion:
We demonstrated that contractile activity can be inhibited via α₁- and α₂-receptors and that this effect is in parted mediated via enteric nerves. Although postoperative changes in α₁- and α₂-adrenergic neurotransmission were observed, these changes appear not to be specific for POI, as they occurred also in SC, without delayed intestinal transit or inflammation. However, these postoperative changes in α-adrenergic neurotransmission might still participate in disturbances of postoperative bowel function. DFG KA2329/5-1