Impaired oxygenation of gastric mucosa in portal hypertension

Abstract

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Acute upper gastrointestinal bleeding in liver cirrhosis patients

“…In portal hypertension, there is splanchnic vasodilatation and arteriovenous shunts development in the submucosa which leads to increased blood flow in this area. This increases the risk of bleeding and at the same time decreases oxygenation of the mucosa with consequent risk of damage 15,16 . The related thrombocytopenia and coagulopathy may also be involved.…”

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-α via the PI 3-kinase-Akt signaling pathway

“…1,[3][4][5] The microvascular abnormalities have been implicated in the increased susceptibility of PHT gastric mucosa to damage. [4][5][6][7][8] Excessive production of nitric oxide (NO) by endothelial NO synthase (eNOS) has been suggested as the basis for the systemic hyperdynamic and abnormal circulation of PHT gastric mucosa. [9][10][11][12] Tumor necrosis factor ␣ (TNF-␣) has been shown indirectly to be a major contributor to the hyperdynamic circulation likely through activation of NO synthase.…”

Tumor necrosis factor ? regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats

“…[1][2][3] The PHT gastric mucosa has distinct morphological and functional abnormalities that increase its susceptibility to damage by noxious factors such as alcohol, aspirin, and ischemia/reperfusion. [4][5][6][7][8][9] We have recently showed that nitric oxide synthase isoform 3 (NOS3) messenger RNA (mRNA) and protein are overexpressed in PHT gastric mucosa of rats, and this overexpression may be, at least in part, responsible for the increased susceptibility of PHT gastric mucosa to damage. 10 However, the mechanisms that activate NOS3 in PHT gastric mucosa are unknown.…”