Aged gastric mucosa: Mechanisms of vulnerability

The incidence, frequency of complications and mortality of gastric ulcer di sease are increased four-fold in the elderly taking non-steroidal anti-infl ammatory drugs (NSAID). There is controversy as to whether this reflects in creased usage of NSAID or specific vulnerability associated with age. We ha ve investigated two possible mechanisms for this increase in gastrointestin al effects in the elderly: (i) increased susceptibility to acute gastrotoxi city; and (ii) reduced adaptation to NSAID, in a model of young (2 month), mature (12 month) and aged (24 month) rats. Aspirin damaged 7.7% of the vol ume of gastric mucosa in the young rat. In mature and aged rats, this incre ased to 11.3% (P < 0.002 compared to control) and 21.9% (P < 0.005 compared to control), respectively. Thus, aspirin caused a three-fold increase in t he severity of acute gastric mucosal injury in aged animals. However, indom ethacin, ibuprofen and L745 337 did not produce any significant acute gastr ic mucosal damage in 2-, 12- or 24-month-old rats. Significant gastric adap tation to diclofenac treatment occurred in both aged and young rats as meas ured by gastric mucosal damage. The aged gastric mucosa adapted equally as well as the young gastric mucosa to diclofenac. The findings of this study provide only modest support to the hypothesis of increased vulnerability of the stomach in the aged. Aspirin was associated with greater damage in the aged. Adaptation to diclofenac-induced damage was not reduced in the aged and there was not an increased susceptibility to damage by the non-aspirin NSAID tested. The selective cyclo-oxygenase-2 inhibitor, L745 337, was the least toxic agent and may represent a group of NSAID which cause fewer gast rointestinal complications in the elderly.