Bicarbonate (HCO3) delivery to the gastroduodenal mucosa by the blood: its importance for mucosal integrity.

Recent results from our laboratory,'-3 as well as data reported by others,4' have shown that gastroduodenal blood flow functions not only provide 0210 and substrates, but also deliver HCO3 to the mucosa. This may be of particular relevance to the pathogenesis of stress ulceration. Sepsis and haemorrhagic shock are frequently associated with systemic acidosis and reduced arterial HCO3 concentration. The recent decline in the rate of severe bleeding from acute gastroduodenal lesions may in part be explained by the more aggressive approach to promptly correct any imbalance of the acid base status in these patients.'" It is clear that reduction of blood flow increases the susceptibility of the gastric and duodenal mucosa to the injurious actions of luminal acid.'2 13 In many experimental models gastric mucosal ulceration after luminal acid exposure alone can only be achieved when blood flow is artificially reduced.4 17 Bile salt or aspirin injury is enhanced by concomitant reduction of blood flow. lR20 The gastric mucosa appears to be relatively resistant to changes in blood flow compared with the duodenum.'5 Thus a 60% reduction of baseline blood flow was necessary to produce damage in a model of hypotensive shock in the rat, whereas the duodenal mucosa ulcerated after relatively minor changes in blood flow. Conversely, increasing blood flow by intraarterial infusion of isoproterenol decreased gastric mucosal damage caused by bile salts, haemorrhagic shock or aspirin in the dog.2122 The fact that sympathectomy attenuated the decrease in blood flow during haemorrhagic shock and also reduced gastric lesion formation is consistent with the protective role of blood HCO3.23 A direct effect on other protective mechanisms such as cellular HCO3 transport mechanisms may also be involved as this has been shown to be under sympathoadrenergic control in the isolated mucosa.24 5 Similar arguments apply to the action of prostaglandins (PG) which effect both the vasculature as well as having direct effects on HCO3 transport by the mucosal cells. Whittle reported an increase in blood flow and associated protection against bile salt and indomethacin induced damage after iv administration of a variety of prostaglandin analogues. Direct infusion of PGI2 into the coeliac artery supplying an in vivo chambered gastric mucosal flap prevented taurocholate and macroscopic acid induced damage in indomethacin pretreated dogs, and this was associated with a large increase in mucosal blood flow. 6 A later report from the same laboratory, however, showed that surface cell damage was induced by taurocholate and acid alone emphasising the importance of microscopic evaluation in the assessment of damage.'714 We do not know whether increased blood flow protects against damage of the surface