The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease.
BACKGROUND
Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role.


OBJECTIVE
To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide.


METHODS
10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years).


METHODS
Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order.


RESULTS
During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)].


CONCLUSIONS
Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.
Trudgill
N J
NJ
Department of Gastroenterology, Northern General Hospital, Sheffield, United Kingdom.
Hussain
F N
FN
Moustafa
M
M
Ajjan
R
R
D'Amato
M
M
Riley
S A
SA
D000328:Adult; D000368:Aged; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects*; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011377:Proglumide / Q000031:analogs & derivatives / Q000627:therapeutic use*
D006727:Hormone Antagonists; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide