Endothelin-1, inducible nitric oxide synthase and macrophage inflammatory protein-1alpha in the pathogenesis of stress ulcer in neurotraumatic patients.
BACKGROUND
To prospectively identify histologically and endoscopically the effect of omeprazole on the expression of endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein-1alpha (MIP-1alpha) in the gastric mucosa of neurosurgical patients with stress ulcer.


METHODS
Twenty-five patients with severe acute intracranial lesions caused by trauma were enrolled in this study. A 40 mg intravenous bolus of omeprazole (OME) was given daily for 7 days. The intragastric pH was continuously recorded for 24 hours on day 1 and 8. Endoscopic evaluation of the gastric corpus, antrum, and duodenal bulb was performed in the ICU, within 24 hours after brain injury, and at follow-up on the 7th day after admission. Paired biopsies were obtained for histologic examinations and immunohistochemical analysis was performed using a LSAB method for MIP-1alpha, ET-1, and iNOS.


RESULTS
There were 72% and 70% of gastroduodenal mucosal lesions at the initial and follow-up endoscopies, respectively. However, the severity of mucosal lesions showed significant improvement in most patients at follow-up (p < 0.05). Mean percentages of time intragastric pH were greater than or equal to 4.0 were 20 +/- 11% and 70 +/- 17% on day 1 and 8, respectively (p < 0.05). The incidences of ET-1, iNOS and MIP-1alpha expression were not significantly different between the patients before and after OME prophylaxis.


CONCLUSIONS
Prophylactic OME is effective in reducing the severity of stress ulcerations in severe neurotraumatic patients. High incidence of tissue ET-1 expression combined with increased activity of iNOS and MIP-1alpha may be responsible for the gastric mucosal injury. We also show that OME fails to counter the enhancement in the mucosal expression of ET-1, iNOS, and MIP-1alpha caused by severe brain damage.
Hsieh
Jan-Sing
JS
From the Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
Howng
Shen-Long
SL
Huang
Tsung-Jen
TJ
Wang
Jaw-Yuan
JY
Chen
Fang-Ming
FM
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009853:Omeprazole / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014947:Wounds and Injuries / Q000150:complications
D000897:Anti-Ulcer Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019332:Endothelin-1; D019402:Macrophage Inflammatory Proteins; D052247:Nitric Oxide Synthase Type II; D009853:Omeprazole