Effects of multiple low doses of flunixin meglumine on repeated endotoxin challenge in the horse

Susan D. Semrad, James N. Moore
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引用次数: 34

Abstract

Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 μ g/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia were observed in all horses, but FM treated horses recovered more rapidly. The leukopenic response after endotoxin was attenuated in Group II following the second dose.

Serum thromboxane (TxB2) decreased after the initial administration of endotoxin and remained below baseline values throughout the study. Serum TxB2 concentrations were not different between the groups. Plasma TxB2 and 6-keto-PGF concentrations were increased after the initial endotoxin injection. In Group II, plasma TxB2 levels declined rapidly after FM administration and remained low. After the second dose of endotoxin, Group I horses had a mild rise and decline in TxB2 and 6-keto-PGF concentrations, respectively. Thromboxane B2 levels in Group II changed little after the second dose of endotoxin, but a dramatic increase in 6-keto-PGF concentrations occurred. These results suggest that multiple low doses of FM to horses with endotoxemia cause a selective and sustained suppression of TxB2 production and an enhancement of 6-keto-PGF.

多次低剂量氟尼辛大胺对马反复内毒素攻击的影响
先前的研究表明,在正常的马中反复使用低剂量的氟尼辛聚氨胺(FM)可以抑制血栓素的产生。停药后血清血栓素浓度升高。我们的研究是为了评估低剂量FM对反复受到内毒素攻击的马的影响。ⅰ组马在0和90 h注射大肠杆菌内毒素(0.1 μ g/kg IV),ⅱ组马在初始给药后2、10、18、26、34和42 h分别注射内毒素和FM (0.25 mg/kg IV)。所有马都观察到内毒素血症的临床症状,但FM治疗的马恢复得更快。第二剂量组内毒素后白细胞减少反应减弱。血清血栓素(TxB2)在初始内毒素治疗后下降,并在整个研究过程中保持在基线值以下。两组间血清TxB2浓度无显著差异。初始内毒素注射后血浆TxB2和6-酮- pgf2 α浓度升高。在第二组,血浆TxB2水平在给药后迅速下降并保持在较低水平。第2次给药后,I组马TxB2和6-酮- pgf2 α浓度分别轻度升高和下降。第二剂量内毒素后,II组血栓素B2水平变化不大,但6-酮- pgf2 α浓度显著升高。这些结果表明,对患有内毒素血症的马进行多次低剂量的FM可选择性地持续抑制TxB2的产生,并增强6-酮- pgf2 α的表达。
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