Paradoxical lower esophageal sphincter contraction induced by cholecystokinin-octapeptide in patients with achalasia

A recent study in cats suggests that cholecystokinin-octapeptide relaxes the feline lower esophageal sphincter (LES) by evoking an indirect neural inhibitory effect that overrides a direct excitatory myogenic effect. We reasoned that, if cholecystokinin-octapeptide has a dual effect on the human LES similar to that in the cat, cholecystokinin-octapeptide might increase LES pressure in patients with impaired inhibitory innervation. To test this hypothesis we determined the effect of intravenous bolus doses of cholecystokinin-octapeptide on LES pressure in three groups of subjects: 7 controls (group 1), 24 patients with untreated idiopathic achalasia (group 2), and 32 miscellaneous patients referred for esophageal manometry (group 3). Lower esophageal sphincter pressure was monitored by a perfused sleeve device. In 6 of 7 control subjects, cholecystokinin-octapeptide caused monophasic LES relaxation. The seventh subject demonstrated a biphasic response of LES relaxation followed by contraction. In 21 of 24 achalasia patients, cholecystokinin-octapeptide induced paradoxical monophasic LES contraction. In 2 achalasia patients, LES pressure did not change after cholecystokinin-octapeptide and in 1 achalasia patient LES pressure decreased, as in normal subjects. In the 32 miscellaneous patients, cholecystokinin-octapeptide induced LES relaxation in 25, a biphasic response in 4, no change in 2, and a paradoxical increase in 1. The patient demonstrating LES contraction to cholecystokinin-octapeptide had an unclassified esophageal motility disorder associated with incomplete LES relaxation after swallows. We conclude: (a) Cholecystokinin-octapeptide induces a paradoxical increase in LES pressure in most achalasia patients; (b) a presser LES response to cholecystokinin-octapeptide suggests post-ganglionic impairment of inhibitory nerves; and (c) achalasia patients demonstrating LES relaxation after cholecystokinin-octapeptide may have neural impairment limited to preganglionic fibers while the postganglionic inhibitory nerves remain at least partially intact.