Abstract
The importance of controlling coagulation/fibrinolysis during severe sepsis has been widely recognized in these days. Regarding antithrombin (AT), it is known to exert positive effects with high dose but can not exert with the low dose. In this study, we tried to get the beneficial effects with low dose (1/4 quantity of maximal effect) of AT in combination with danaparoid sodium (DS). [Method] Sepsis model was made with the injection of sublethal dose of lipopolysaccharide (LPS) into rats. Concomitant use of 125U·kg-1 of AT was made in AT group. AT and 400U·kg-1 of DS were simultaneously infused in AT/DS group. The status of mesenteric microcirculation was observed 1, 2, 3hrs after LPS injection under the intravital microscope. Blood samples were drawn after 3hrs and the indicators of coagulation, inflammation and organ dysfunction were measured. [Results] AT activity was decreased to 70% in control group, whereas approximately 100% was maintained in AT group, and 150% was attained in AT/DS group. FDP and fibrinogen levels in AT group were similar to those of control group. These coagulation markers were significantly improved with DS administration. WBC and platelet number showed steep drop reflecting the adhesion to vascular wall, and these changes were significantly alleviated in AT/DS group. Blood velocity in arteriole and venule were maintained in AT/DS group. IL-6 level was decreased in all treated groups, while the increased level of prostaglandin I2 (PGI2) was recognized only in AT/DS group. Organ dysfunction was significantly improved in DS treated groups and bleeding event did not increase in these groups. [Conclusion] Even the low dose of AT can improve the septic organ dysfunction through the inhibition of hypercoagulation, suppression in inflammation and maintenance of microcirculation, when administered with DS.
