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  • Title: Endotoxin-induced hemodynamic and prostaglandin changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone.
    Author: Templeton CB, Bottoms GD, Fessler JF, Ewert KM, Roesel OF, Johnson MA, Latshaw HS.
    Journal: Circ Shock; 1987; 23(4):231-40. PubMed ID: 3319278.
    Abstract:
    Shock was induced in four groups of anesthetized ponies with an intravenous injection of Escherichia coli endotoxin [125 micrograms/kg]. Five minutes after endotoxin injection, the ponies were given no treatment (group A), flunixin meglumine (FM:1.1 mg/kg) (group B), dexamethasone (2 mg/kg) (group C), or prednisolone (10 mg/kg) (group D). Additionally, FM was given every 3 hours, and the steroids were given at 3, 9, and 24 hours following endotoxin. Hemodynamic measurements were made during the 4-hour anesthetic period. Blood samples were collected for the analysis of prostaglandins, blood chemicals, and enzymes until death. Microspheres labeled with one of four radionuclides were used to determine regional blood flow at 0, 0.1, 1, and 2 hours after endotoxin was given. Plasma levels of both thromboxane and prostaglandin I2 increased from less than 1 ng/ml to between 3 and 5 ng/ml following the injection of endotoxin. The elevated thromboxane corresponded with high pulmonary arterial pressure [between 35 and 55 mm Hg] and low mean systemic arterial pressure (between 40 and 65 mm Hg) during the first 5-10 minutes following endotoxin. Increased concentrations of prostaglandin I2 were temporally related to systemic arterial hypotension, which occurred 1-2 hours following endotoxin in all groups except group B. The rise of prostaglandin I2 and hypotension were not observed in the flunixin meglumine-treated ponies. Dexamethasone was less effective, and prednisolone was ineffective in preventing the synthesis of prostaglandin I2 and the accompanying hemodynamic changes that occurred during the first 2 hours following endotoxin. This is probably due to the fact that steroids require a longer period of time before prostaglandin synthesis is reduced. Although not statistically significant, increased survival trends were observed in ponies treated with flunixin meglumine.
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