The effect of chemical and surgical sympathectomy on gastric secretion and innervation.

The purpose of this project was to evaluate the effects of chemical and surgical sympathectomy on gastric acid secretion (GAS) and mucosal innervation in the dog. Chemical sympathectomy was achieved with 6-OHDA and surgical sympathectomy was performed by excising the celiac and superior mesenteric ganglia. Gastric biopsies for fluorescence microscopy were taken before and after sympathectomy, as was pentagastrin (PPG) stimulated GAS. Each sympathectomy increased GAS in response to submaximal doses of PPG while simultaneously destroying adrenergic nerve terminals in the gastric mucosa. 6-OHDA caused a complete degeneration of nerve terminals at one week, but regeneration was complete by 9 weeks. The data support the concept that the sympathetic innervation of the stomach is an inhibitor of GAS.

A pharmacokinetic analysis of the vagal release of 5-hydroxytryptamine in the cat.

The kinetics of 5-hydroxytryptamine (5-HT) release into the portal system after efferent electrical vagal stimulation were studied in an in vivo model. Blood samples were drawn from cats before, during and after vagal nerve stimulation, and portal plasma levels of 5-HT were measured. Portal plasma concentration of 5-HT rose during stimulation. After termination of stimulation, the plasma levels returned to steady state values and were used to calculate half-life and elimination rate constant. When pharmacokinetic principles were applied, the plasma half-life (T1/2) was determined to be 1.32 min and the elimination rate constant (KE), 0.5246 min-1. Pharmacokinetic principles also were applied to data from earlier in vitro studies using exogenously administered 5-HT, and a half-life of 1.03 min and a KE of 0.67 min-1 were calculated. Therefore, it appears that exogenously administered 5-HT and neurogenically released endogenous 5-HT are metabolized at a similar rate, both having a short half-life.

Gastric acid secretion after chemical sympathectomy.

Adrenergic nerve terminals in several organs are selectively destroyed by 6-hydroxydopamine (6-OHDA) resulting in a chemical sympathectomy that is reversible. In this study the acute and chronic effects of 6-OHDA on gastric mucosa and acid secretion were evaluated. Four dogs were given 6-OHDA (40 mg/kg, intravenously). Gastric biopsies were taken before treatment and biweekly thereafter and were analyzed by fluorescence microscopy (Hillarp-Falck). Degeneration of adrenergic nerve terminals in the mucosa was complete at 1 week. Early regeneration was noted at 3 weeks and appeared to be complete at 9 weeks. In another group of seven dogs with a gastric fistula, dose-response curves to pnetagastrin (PPG, 0 to 5 microgram/kg/hr) were determined. Then 6-OHDA (40 mg/kg) was given to these dogs and secretory studies were repeated weekly thereafter for 8 weeks. After 6-OHDA administration, acid secretion increased in response to submaximal doses of PPG, whereas maximal secretion was unchanged. The peak increase occurred the second week; thereafter secretion gradually returned to control values. We conclude that chemical sympathectomy (6-OHDA) increases gastric acid secretion in response to submaximal PPG stimulation. This increase correlates well with the 6-OHDA--induced degeneration of adrenergic terminals in the mucosa. These data suggest that the adrenergic innervation of the stomach has an inhibitory effect on the control of acid secretion in the dog.

Effects of celiacectomy and stellatectomy on gastric mucosal innervation and acid secretion in the dog.

The effect of surgical excision of the celiac and superior mesenteric ganglia and the stellate ganglia, respectively, on gastric acid secretion and adrenergic innervation of gastric mucosa was studied in five dogs. After removal of the abdominal ganglia, there was a significant increase in acid secretion while there was a marked decrease in the number of adrenergic nerve terminals in the mucosa. When, addition, the stellate ganglia were excised, acid secretion increased slightly in two dogs, while little change in mucosal innervation was noted. These data suggest that the adrenergic innervation of the stomach has an inhibitory role in the control of acid secretion in the dog. Vagal adrenergic nerve fibers seem to be of limited importance in gastric acid production.

Origin of the adrenergic nerve fibers in the subdiaphragmatic vagus in the dog.

The vagi at the subdiaphragmatic level were studied by the Hillarp-Falck technic in combination with a nerve crush procedure in three normal dogs and in eight dogs that had undergone previous surgical excision of the superior cervical ganglion and/or the stellate ganglia. Unilateral ganglionectomies were performed so that the contralateral vagus served as a control. Based on these results, it is concluded that: (1) the subdiaphragmatic canine vagus contains numerous adrenergic nerve fibers; (2) the main portion of these vagal adrenergic fibers arises from the stellate ganglia; and (3) removal of both the stellate and the superior cervical ganglia results in nearly complete adrenergic denervation of the abdominal vagus.