Platelet-activating factor mediates gastric damage induced by hemorrhagic shock.
The role of platelet-activating factor (PAF) as a mediator of the gastric damage associated with hemorrhagic shock was investigated using a rat model. With use of an ex vivo gastric chamber preparation, the gastric mucosa was bathed with 0.1 M HCl for 90 min. At minute 10 the systemic arterial blood pressure (BP) was reduced to 25 mmHg by bleeding from the femoral artery. BP was maintained at this level for 15 min, then the shed blood was reinfused. In control rats subjected to this protocol, extensive gastric damage developed during and after the shock period and involved an average of 50 +/- 8% of the total area of glandular mucosa. A marked decrease in transmucosal potential difference (PD) was observed during shock, with little recovery thereafter. Also, significant appearance of protein and hemoglobin (Hb) in the gastric lumen was detected after induction of shock. Oral pretreatment of the rats with the PAF antagonist WEB 2086 (0.5-20 mg/kg) dose dependently reduced the extent of macroscopically visible gastric damage, the decrease in transmucosal PD, and the appearance in the lumen of protein and Hb. A similar protective effect was observed with another PAF antagonist, BN 52021 (10 mg/kg). With use of laser-Doppler flowmetry, changes in gastric blood flow were determined before, during, and after induction of shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Wallace
J L
JL
Gastrointestinal Research Group, University of Calgary, Alberta, Canada.
Hogaboam
C M
CM
McKnight
G W
GW
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004224:Diterpenes; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology*; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013270:Stomach / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C045856:ginkgolide B