Abstract
It is recognized that changes in vascular endothelial cell function and imbalance of coagulation/fibrinolysis play significant roles in the developmenf septic organ dysfunction. In a previous study, we presented the significant effects of antithrombin III (AT-III) on survival rate and on improvement in organ dysfunction in a dose dependent manner in endotoxemic rats. [Purpose] The purpose of this study was to clarify the mechanism of these AT-III' s effects in endotoxemic rats. Furthermore, since the modulating effects of AT-III, other than anti-thrombotic effects, on endothelial function were expected only with so-called a “supranormal level of AT-III, ” we tried to demonstrate these effects. [Methods] Rats were cannulated and then a low dose of endotoxin was infused continuously for 4hrs. In the treatment group, either 2.5 (low-dose group) or 10.0 (high-dose group) IU/kg/hr of AT-III was infused simultaneously with endotoxin for 4hrs, while saline was infused in the untreated group. After the infusion period, liver was examined using an in vivo microscope, and sinusoidal blood flow and width, and neutrophil adhesion were evaluated with a computed micro circulation analysis system. [Results] Comparison of sinusoidal blood flow showed a significant increase in the high-dose group compared to either the untreated or the low-dose group (p<0.01), while no significant difference was observed between the untreated group and the low-dose group. Comparison of sinusoidal width showed significant improvement in both the low-dose group and the high-dose group compared to the untreated group (p<0.05, 0.01, respectively). Adhesive neutrophil counts were significantly suppressed in the high-dose group. In summary, AT-III supplement had a protective effect on sinusoidal circulation through the maintenance of blood flow and suppression of vasoconstriction. Moreover, modification of endothelial function related with neutrophil adhesion was recognized under the supranormal level of AT-III in endotoxemic rats.
