Stress ulceration and gastric mucosal cell kinetics: the influence of prophylaxis against acute stress ulceration.
Acute gastric stress ulceration occurs frequently in severely ill patients. Mucosal ischemia is central to the etiology of stress ulceration. The ability of the mucosa to restore continuity when damaged is one of the most important of the local defence mechanisms against injury. The aims of this study were to investigate this restitutive process during stress ulcer formation and to determine the effect of prophylaxis against stress ulceration on gastric mucosal cell kinetics. Nuclear DNA was radiolabeled in vivo with tritiated thymidine, and after autoradiography the position and number of labeled cells along the gastric mucosal gland were determined. Wistar rats were studied immediately and 48 hr after cold restraint stress. The labeling index in the proliferative zone of the gastric mucosa was significantly suppressed immediately after stress (12.58% vs 16.81% for unstressed controls, P < 0.001). This effect persisted for 48 hr after stress (9.89% vs 16.35% for unstressed controls, P < 0.001). Prophylaxis against stress ulceration with cimetidine or allopurinol prevented this suppression of gastric mucosal cell kinetics and promoted early migration of labeled cells towards the surface of the mucosal gland. Allopurinol prophylaxis was associated with migration of mucosal cells immediately following stress greater than that following cimetidine prophylaxis (14.0% vs 9.3% surface layer labeling index, P < 0.01). Allopurinol, a xanthine oxidase inhibitor, reduces oxygen free radical production during ischemia reperfusion injury. These results emphasise the importance of the gastric mucosal defence mechanisms in protection against injury and indicate the role of ischemia in the aetiology of acute gastric stress ulceration.
Flynn
R
R
University Department of Surgery, Trinity College Dublin, St. James's Hospital, Ireland.
Stuart
R C
RC
Gorey
T F
TF
Kay
E
E
McBennett
S
S
Byrne
P J
PJ
Hennessy
T P
TP
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D002927:Cimetidine / Q000627:therapeutic use; D004247:DNA / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000473:pathology*; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D013312:Stress, Physiological
D000493:Allopurinol; D002927:Cimetidine; D004247:DNA