Potential mechanisms responsible for zymosan-associated endothelial injury in rats

Objective:

To assess alterations in endothelial barrier integrity and potential 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 intravascular plasma volume, interstitial fluid volume, and extravascular ¹²⁵I-labelled human serum albumin distribution as well as plasma concentrations of albumin, α₁-macroglobulin, α₂-antiplasmin, and antithrombin III, 24 hours after the intraperitoneal injection.

Results:

Endothelial permeability significantly increased in abdominal organs and the gastrointestinal tract, and plasma antiplasmin concentrations decreased. Pretreatment with N-acetyl-L-cysteine, dimethyl sulphoxide, or indomethacin protected against zymosan-induced endothelial barrier injury and the decline in protease inhibitors in plasma to varying degrees, while pretreatment with verapamil or allopurinol had a limited effect.

Conclusion:

Oxygen free radicals, prostaglandin, and proteases may have roles in the pathogenesis of zymosan-induced endothelial barrier injuries, implying that several mediators probably are interacting. Copyright © 1999 Taylor and Francis Ltd.