Epidermal growth factor protects portal hypertensive gastric mucosa in ischemia/reperfusion: the role of capillary endothelia and prostaglandins.
BACKGROUND
Epidermal growth factor (EGF) protects gastric mucosa against a variety of injurious agents, but the mechanism is unclear. Because the abnormal microvasculature of portal hypertensive (PHT) gastric mucosa is a major target of ischemia/reperfusion (I/R) injury, we used this model to assess EGF's protective role at the microvascular level.


METHODS
Rats with PHT (staged portal vein ligation) received either EGF, 20 micrograms/kg, or saline solution intravenously, with or without indomethacin pretreatment (20 mg/kg subcutaneously). I/R was produced by withdrawing blood to systemic pressures of 30 mm Hg for 20 minutes and reinfusing it. Stomachs were excised 20 minutes later and evaluated for gross and histologic necrosis, microvascular permeability, mucosal ultrastructure and vimentin, and cyclooxygenase immunofluorescence.


RESULTS
In saline-treated rats, gross and histologic damage involved 46% +/- 3% of glandular mucosa and 23% +/- 3% of mucosal sections, respectively. Microvascular permeability was increased 43-fold over that of normal control rats. Vimentin immunofluorescence intensity was reduced to 36% +/- 4% that of normal control rats. EGF pretreatment reduced histologic necrosis to 2% +/- 1% (p less than 0.01). Microvascular permeability and vimentin intensity were almost normalized. Indomethacin partially reversed the mucosal protection induced by EGF.


CONCLUSIONS
EGF significantly reduces I/R injury to PHT gastric mucosa. Microvascular endothelia of PHT gastric mucosa are the major target of I/R injury and the site of EGF's protective action. Prostaglandins in part mediate EGF's protective action.
Ishikawa
T
T
Surgical Service, DVA Medical Center, Long Beach, CA 90822.
Sarfeh
I J
IJ
Tarnawski
A
A
Golshan
R
R
Douglas
T
T
Sugiyama
M
M
D000818:Animals; D002196:Capillaries / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D006975:Hypertension, Portal / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014746:Vimentin / Q000378:metabolism
D011453:Prostaglandins; D014746:Vimentin; D004815:Epidermal Growth Factor