PLATELET ACTIVATING FACTOR-INDUCED SHOCK AND INTESTINAL NECROSIS IN THE RAT - ROLE OF ENDOGENOUS PLATELET-ACTIVATING-FACTOR AND EFFECT OF SALINE INFUSION

Background and Methods: The mechanism of ischemic bowel necrosis induced by platelet-activating factor is unclear. Since intestinal hypoperfusion is observed after platelet-activating factor injection, we hypothesized that mesenteric vasoconstriction is the mechanism of bowel injury. The present study investigated the effects of saline infusion on platelet activating factor-induced bowel necrosis and its mechanism. Male Sprague-Dawley rats were divided into four groups: group A consisted of sham-operated rats; group B received platelet-activating factor (1.5-mu-g/kg iv); group C received platelet-activating factor and saline (0.097 mL/min iv); group D received platelet-activating factor and WEB 2086 (platelet-activating factor antagonist). Results: Saline infusion largely reversed platelet activating factor-induced hypotension, hemoconcentration, and reduction of the superior mesenteric arterial blood flow. Saline infusion also ameliorated platelet activating factor-induced bowel injury, although a mild-to-moderate degree of necrosis still developed focally. In addition, saline prevented the platelet activating factor-induced increase in intestinal platelet-activating factor production. Saline also prevented the increase in intestine leukocyte number, as estimated by myeloperoxidase activity. Conclusions: Saline infusion is an effective treatment for platelet activating factor-induced shock and intestinal necrosis. However, focal bowel injury is still observed, suggesting that other factors besides hemodynamic changes contribute to the development of tissue injury. We also showed that, in vivo, platelet-activating factor stimulates its own synthesis via a positive feedback loop, which could be blocked by intravascular volume expansion with saline.