Long-term effects of highly selective vagotomy (HSV) in dogs on acid and pepsin secretion

Abstract

Gastric H⁺ and pepsin studies before and at intervals for 40 months after fundic vagotomy (HSV) in 3 fistula dogs were done with the vagal stimulant 2-deoxyglucose (2-DG), and with dose responses to urecholine, histamine, and pentagastrin. Initially HSV completely blocked the secretory response to 2-DG, but secretion began to recover by 5–6 months, and from 16 months on stabilized at 60% H⁺ and 13–17% pepsin (preoperative = 100%). After HSV the stomach showed hypersensitivity to urecholine with a lower threshold and lowerK_m, but unchangedV_m, while with histamine the curves were shifted to the right, withK_m unchanged andK_m increased. With pentagastrin there was also a small decrease inV_m. Pepsin responses to urecholine recovered and exceeded control by 16 months, but remained relatively unresponsive to histamine or pentagastrin. A cholinergic background provided by urecholine at subthreshold doses (<10 μg/kg·hr) restored both pentagastrin and histamine responses to prevagotomy levels. Gastrin release from the innervated antrum by 2-DG was several times greater than in controls and was atropine sensitive. The results indicate that denervation of the secretory mucosa, especially of the peptic cells, is never more than partially reversed even after 3 years. Even though the response to vagal stimulation is partial, the mucosa remains capable of normal response, ie, there is no atrophy, and therefore, the vagus is not directly trophic to the gastric fundus. Moreover, vagotomy was followed by some hypersensitivity to urecholine, indicating changes in cholinergic receptors like those seen in denervated muscle cells.