Effects of fundic vagotomy and cholinergic replacement on pentagastrin dose responsive gastric acid and pepsin secretion in man.

The effects of fundic vagotomy on acid and pepsin secretion in 12 patients (10 males, two females; nine duodenal ulcer, three gastric ulcer) were studied using a pentagastrin dose response before and after Vagotomy. In the intact stage H, Cl, and pepsin output all had the same ED50, 120-127 pmol/kg/h. Vagotomy reduced basal output of acid by 78%, Cl- by 50%, and pepsin by 62%. Postvagotomy basal outputs were not related to preoperative levels, while maximum acid output was reduced by an average of 35%, proportionally to the preoperative output (r = 0.94). Vagotomy uncompetitively (ED50 increase, Vmax decrease) inhibited the pentagastrin dose response of acid, chloride, and pepsin output. Postoperatively, a six-fold greater dose of pentagastrin (450 vs 76 pmol/kg/h) was required to stimulate acid to 50% of its preoperative maximum output. For pepsin secretion the increase was 12-fold (185 vs 15 pmol/kg/h). In five of the nine duodenal ulcer patients pentagastrin dose responses were repeated with a background infusion of urecholine, 20 micrograms/kg/h. Urecholine increased basal and peak acid, pepsin, and chloride outputs, and the ratio of basal: maximal almost to prevagotomy levels; it also restored the sensitivity to pentagastrin. Serum gastrin was not significantly changed by urecholine or by vagotomy. We conclude that the level of basal acid and pepsin secretion in ulcer patients, which is largely eliminated by vagotomy, is dependent on the vagus and not on serum gastrin. The effects of vagotomy are functional, are due to cholinergic withdrawal, and usually can be restored by cholinergic replacement.