Endothelial Barrier Dysfunction in Multiple Organ Injury. An Experimental Study in Rats

Multiple organ dysfunction syndrome (MODS) is still the leading cause of mortality in the surgical intensive care unit. The effect on among others endothelial barrier permeability, reticuloendothelial function, organ function and protease-antiprotease activities was studied following a variety of challenges, especially over-activation of macrophages induced by intraperitoneal administration of zymosan., A variation in endothelial barrier resistance (RE) between various organs/tissues and between various types of injuries was demonstrated, representing an organ/tissue dependent RE responsible for the sequence of organ failing. The compromise in endothelial permeability in the various organs studied appeared earlier than corresponding alterations in organ function. Hyperactivation of macrophages seem to represent a major pathogenetic factor responsible for endothelial barrier injury. Cellular immunological modulation demonstrated a pattern of over-regulation followed by down-regulation after higher doses of zymosan. The action of oxygen free radicals, prostaglandins and plasma proteases seems to contribute to the endothelial barrier injury induced by macrophage over-activation and the resulting MODS-like condition caused by zymosan is related to pronounced proteolytic activity and particularly extensive activation in the coagulation, kallikrein and fibrinolytic systems. Administration of antioxidants or anti-inflammatory agents seemed to possess protective effects and improved the outcome of the MODS-like condition