The effects of sucralfate and luminal stasis on recovery of the chambered rat gastric mucosa from taurocholate-induced damage.

We have previously shown, using a gastric chamber model, that both sucralfate and luminal stasis protected the rat gastric mucosa against the development of hemorrhagic erosions produced by subsequent exposure for 10 minutes to acidified (50 mM HCl) 80 mM sodium taurocholate (NaT). The protection afforded by sucralfate was abolished by inhibition of cyclooxygenase activity but restored by sucralfate. In this study we demonstrate that indomethacin pretreatment decreases both the depth (in microns) and magnitude (in pH units) of the juxtamucosal pH gradient, but that sucralfate restores these parameters to levels characteristic of normal mucosae. The cytoprotective effect of sucralfate is thus prostaglandin-independent and, at least in part, a consequence of sucralfate-induced increases in the thickness of the juxtamucosal pH gradient/unstirred layer. We have also examined the ability of sucralfate to prevent the otherwise inevitable development of hemorrhagic erosions when it was applied after the gastric mucosa was exposed to NaT. When 100 mg sucralfate in 50 mM HCl was applied for 10 minutes, without stirring, subsequent to a 10-minute exposure of the mucosa to NaT, the average lesion area was reduced from about 15% to less than 3%. Unlike its cytoprotective property, the ability of sucralfate to accelerate the recovery process after damage was abolished by indomethacin pretreatment. Studies using antimony microelectrodes revealed that indomethacin pretreatment resulted in reductions in both the depth and magnitude of the pH gradient that resulted from plasma efflux from the mucosa after exposure to the acidified bile salt. These studies demonstrate that sucralfate is capable not only of prevention or attenuation of acute damage when administered prior to damaging agents, but is also capable of arresting the sequence of events that produces hemorrhage in the previously inflamed or damaged stomach.