Potential mechanisms responsible for zymosan-associated endothelial injuryin rats

Objective: To assess alterations in endothelial barrier integrity and poten tial factors involved in zymosan-associated endothelial injury. Design: Experimental study. Setting: University hospital, Sweden. Animals: 42 adult male Sprague-Dawley rats. Interventions: One hour before an intraperitoneal injection of paraffin or zymosan (0.25 mg/g body weight), 1.0 ml of a solution of saline, N-acetyl-L -cysteine, dimethyl sulphoxide, indomethacin, verapamil, or allopurinol was given intravenously. Main outcome measures: Measurement of tissue water content, tissue intravas cular plasma volume, interstitial fluid volume, and extravascular I-125-lab elled human serum albumin distribution as well as plasma concentrations of albumin, alpha(1)-macroglobulin, alpha(2)-antiplasmin, and antithrombin III , 24 hours after the intraperitoneal injection. Results: Endothelial permeability significantly increased in abdominal orga ns and the gastrointestinal tract, and plasma antiplasmin concentrations de creased. Pretreatment with N-acetyl-L-cysteine, dimethyl sulphoxide, or ind omethacin protected against zymosan-induced endothelial barrier injury and the decline in protease inhibitors in plasma to varying degrees, while pret reatment with verapamil or allopurinol had a limited effect. Conclusion: Oxygen free radicals, prostaglandin, and proteases may have rol es in the pathogenesis of zymosan-induced endothelial barrier injuries, imp lying that several mediators probably are interacting.