1990 Volume 87 Issue 8 Pages 1662-1669
Oxyradicals of neutrophils are supposed to play a role in the formation of gastric mucosal injury induced by ischemia-reinfusion (I-R). Recently, platelet-activating factor (PAF) is suggested to be involved in the I-R injury as one of chemical mediators since this substance may be produced in hypoxic tissue. stimulating oxyradical generation of neutropils. In the present study, using CV-3988, a PAF antagonist, the severity of gastric mucosal damage and chemiluminescence (CL) activity of neutrophils of circulating blood were measured to evaluate the role of PAF in the I-R injury.
SD rats fasted overnight were anesthetized and instilled 0.1N HCl into the stomach. Rats were then subjected to reduction of blood pressure to 20-30mmHg for 20min by bleeding followed by reinfusion of shed blood for 20min. Two groups of rats each received 10mg/kg CV-3988 (PAF-A grup) or saline (I-R group) i.v. 5min prior to bleeding. After killing rats, the area of gross gastric lesions and the index of histologic damage were assessed. In separate PAF-A and I-R groups of rats, and control rats received saline i.v. and no hypotension, blood samples were collected from the portal vein and the abdominal aorta 45min after acid instillation. Luminol-dependent CL stimulated by PMA of blood samples was measured using the photometer Monolight 401. CL activity was expressed as [peak CL/neutrophils number].
The area of gross lesions was significantly smaller in the PAF-A group than in the I-R group in the corpus (120 vs. 363mm2), but not in the antrum (10 vs. 10mm2). However, the index of histologic damage both in the corpus and antrum was significantly smaller in the PAF-A group than in the I-R group (corpus, 0.9 vs. 1.8; antrum, 0.9 vs. 2.0). CL activity of neutrophils either from the portal vein or the aorta was significantly greater in the I-R group than in PAF-A and control group groups (I-R, control, PAF-A: protal, 17.3, 6.6, 5.3×10-4 RLU; aorta, 40, 8.1, 9.1×10-4 RLU).
PAF plays in part a role for the formation of ischemia-reinfusion injury in the rat stomach. Oxyradicals generation stimulated by PAF of neutrophils may be involved in this mechanism.