Activation of an adrenergic and vagally‐mediated NANC pathway in surgery‐induced fundic relaxation in the rat

Abstract

The aim of this study was to pharmacologically characterize and investigate the possible contribution of adrenergic and nonadrenergic noncholinergic (NANC) pathways involved in the relaxation of the rat gastric fundus following abdominal surgery. Using an intragastric balloon, the effect of skin incision (SI), laparotomy (LT) and manipulation of the small intestine followed by caecal resection (M + R) on fundic pressure was evaluated. SI resulted in a brief relaxation of the gastric fundus abolished by guanethidine and blocked by hexamethonium and the combination of phentolamine, propranolol and atropine (PPA). LT induced a longer lasting relaxation which was abolished by guanethidine and hexamethonium. It was blocked by PPA and the combination of ganglionectomy and vagotomy, but unaffected by atropine, vagotomy or ganglionectomy. M + R induced a long-lasting relaxation which was only partly blocked by guanethidine or PPA, illustrating an inhibitory NANC component. Vagotomy combined with guanethidine completely abolished the relaxation following M + R, whereas it was significantly blocked by hexamethonium and the combination of ganglionectomy with vagotomy. These results indicate that SI, LT and M + R induce inhibition of fundic motility via an adrenergic mechanism. During M + R, an additional vagally mediated inhibitory NANC pathway is activated. Finally, we suggest that LT and M + R inhibit the gastric fundus via both a splanchnic and a vagal reflex pathway.

Neuroimmune mechanisms in postoperative ileus

“…Activation of these nerves subsequently inhibits motility of the entire gastrointestinal tract. In addition to this adrenergic inhibitory pathway, intense stimulation of splanchnic afferents triggers an inhibitory non-adrenergic, vagally mediated pathway22(fig 2B). …”

The role of lymphoid tissue in the attenuation of the postoperative ileus

“…Postoperative ileus is marked by a neurogenic phase and a clinically relevant prolonged inflammatory phase. Neuronal mechanisms cannot exclusively explain the perpetuation of postoperative ileus because of early neuronal recovery shortly after wound closure (5,6,15). We previously reported a timeand trauma-degree-dependent inflammatory cascade (29,30), infiltration of leukocytes (34 -36, 65, 78), macrophages (19,20,31,81), immunologically competent cells (18,29,30,34,60,62,65,76,78), and an upregulation of proinflammatory cytokines within the intestinal muscularis (30, 32-34, 59, 61, 64, 75-77, 80, 82).…”

Evidence for mast cell involvement in human postoperative ileus: a novel link

“…Although the hierarchy and sequence of these reflexes remain a matter of debate, consistent evidence indicates that activation of prevertebral and spinal circuits, running through splanchnic (sympathetic) nerves, exerts a prominent inhibitory effect leading to postoperative gastrointestinal dysmotility. A spinal reflex, resulting in the activation of adrenergic inhibitory pathways, can be triggered by skin incision and laparotomy, which are usually accompanied by short-lived impairment of gut motility 10. This reflex-mediated inhibitory effect is abolished by a number of nerve-damaging techniques including division of splanchnic nerves, severing of dorsal root fibres and spinal cord crushing 1.…”

“…As a result, efferent adrenergic pathways would contribute to POI via inhibition of gastrointestinal motility. In addition to adrenergic reflexes, other non-adrenergic neural mechanisms, involving the release of nitric oxide (NO),10 14 vasoactive intestinal polypeptide15 16 and endogenous opioid peptides, contribute to the pathophysiology of POI. Finally, hyperactivity of the sympathetic nervous system, resulting in a strong inhibition of enteric nervous circuitries via α 2 -adrenoceptor-mediated presynaptic suppression of excitatory transmission (and direct postsynaptic inhibition of neuronal activity), appears to be involved in POI 10…”