Antithrombin III Effects on the Production of Vasoactive Substances in Endotoxemic Rats.
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概要
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Antithrombin III (AT-III) supplementation in severe sepsis has been thought to modulate not only coagulatve function but also other endothelial cell functions such as cytokine production or expression of adhesion molecules. The purpose of this study is to reveal the effects of AT-III on vasoactive substances production during sepsis. [Material and methods] Wistar rats received either 250U/kg (AT250) or 500U/kg (AT500) of AT-III from a central venous catheter, while the control group received saline alone. Concurrently, either 10.0, 5.0 or 1.25mg/kg of endotoxin was continuously infused for 24hrs, and then, the survival rate was evaluated. After 1.25mg/kg of endotoxin infusion, blood samples were collected in the AT250, AT500 and control groups. Serum levels of 6-keto-PGF1α, which is a stable metabolite of PGI2, and endothelin-1 were measured by ELISA and RIA, respectively. In addition, AT-III activity, thrombin-antithrombin III (TAT) complex, ALT, BUN were examined in the same blood samples. [Results and discussion] Survival rate was significantly improved by AT-III supplementation as follows: 0% in control group, 50% in AT250 group and 100% in AT500 group at the dose of 10.0mg/kg of endotoxin. Furthermore, AT-III activity increased over 200% in both the AT250 and AT500 groups. There was no difference in TAT levels between the three groups. Hepatic dysfunction was expressed by ALT in both the AT250 and the AT500 groups (p<0.05), increased BUN was suppressed only with AT500 (p<0.05). After endotoxin infusion the 6-keto-PGF1α level was almost 2 times higher than the normal level, and this elevation was further increased with AT500 (p<0.05). In contrast, although the endothelin-1 level was 7 times higher with endotoxin infusion, no change was observed with AT-III supplementation. From these results, we conclude that large amounts of AT-III improve survival rate and organ dysfunction through the upregulation of PGI2 production by endothelial cells and the regulation of the coagulation system.
- 一般社団法人 日本救急医学会の論文
一般社団法人 日本救急医学会 | 論文
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- The Effect of Antithrombin III on Cytokine Production in Endotoxemic Rats.
- Antithrombin III Effects on the Production of Vasoactive Substances in Endotoxemic Rats.