Cimetidine-induced bicarbonate production in canine gastric pouches

Abstract

Secretion of HCO 3 − into a mucus-gel “unstirred layer” has been proposed as part of the gastric mucosal defense system. Cimetidine has a cytoprotective effect on salicylate-challenged gastric mucosa independent of its acid-inhibiting property. This study was done to (1) evaluate whether cimetidine increases gastric mucosal HCO 3 and to (2) ascertain if ionic shifts accompany the HCO 3 − to explain the mechanism of its production. Six dogs with Heidenhain gastric pouches were fasted 24 hr prior to testing. Pouch access was provided by a cannula fitted with an airtight apparatus for test solution instillation and removal and transmucosal potential difference (PD) measurement. A test solution composed of 175 m M mannitol, 25 m M NaCl, and 50 m M EPPS buffer was used, its pH adjusted to above 8.0; 14C-labeled polyethylene glycol was added for volumetric determinations. Nine 15-min periods comprised each test: four control periods of iv saline infusion; a fifth period when an iv cimetidine bolus was given; and four test periods when doses of 2.5, 5, or 10 mg/kg/hr cimetidine were infused iv. Test solution (50 ml) was placed in the pouch and an initial sample taken; 15 min later a final sample was taken, the pouch rinsed, and the next period begun. Concentrations of HCO 3 −, Na +, K +, and Cl − were determined for each sample as well as changes in osmolality, pH, volume, and PD. Mean net HCO 3 − increased from 79 μmol/15 min during saline infusions to 109, 124, and 123 μmol/15 min with 2.5, 5, and 10 mg/kg/hr cimetidine iv; all are significantly increased compared to saline controls ( P < 0.01). None of the other measured parameters changed significantly after cimetidine infusion. Cimetidine causes modest but significant increases in gastric mucosal HCO 3 −. The clinical role, if any, of these increases in HCO 3 − in gastric mucosal defense remains to be determined.