Endotoxin-induced hemodynamic and prostaglandin changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone.

The research paper explores the impacts of various treatments on shock in ponies induced by an injection of Escherichia coli endotoxin. It concludes that Flunixin Meglumine was the most effective treatment in preventing the synthesis of prostaglandin I2 and associated hemodynamic changes during the early stages after endotoxin exposure.

Experiment Setup and Procedure

• Focusing on the effects of flunixin meglumine, dexamethasone and prednisolone, the researchers set up four groups of anesthetized ponies. Each group received an intravenous injection of Escherichia coli endotoxin to induce shock.
• Five minutes after the endotoxin injection, the ponies were either given no treatment (group A), flunixin meglumine (group B), dexamethasone (group C), or prednisolone (group D). Flunixin meglumine was given every three hours, while the steroids were administered at 3, 9, and 24 hours following the endotoxin.
• Hemodynamic measurements were taken during a 4-hour anesthetic period, and blood samples were collected until the subject’s death for the analysis of blood chemicals, enzymes, and prostaglandins.
• Regional blood flow was determined at 0, 0.1, 1, and 2 hours after endotoxin injection using microspheres labeled with one of four radionuclides.

Results

• After the injection of endotoxin, plasma levels of thromboxane and prostaglandin I2 increased from less than 1 ng/ml to between 3 and 5 ng/ml. Elevated thromboxane corresponded to high pulmonary arterial pressure and low mean systemic arterial pressure during the first few minutes following endotoxin injection.
• The increased concentrations of prostaglandin I2 were observed to be temporally related to systemic arterial hypotension, which occurred 1-2 hours after endotoxin injection in all groups except group B.
• In the flunixin meglumine-treated group, the rise of prostaglandin I2 and hypotension were not observed, suggesting its effectiveness in mitigating these effects.
• Compared with flunixin meglumine, dexamethasone was found to be less effective, and prednisolone was found to be ineffective in preventing these hemodynamic changes and prostaglandin I2 synthesis during the first 2 hours post-endotoxin injection, potentially due to the steroids requiring more time to reduce prostaglandin synthesis.
• Although the results were not statistically significant, there were observed trends of increased survival rates in the ponies treated with flunixin meglumine.