Endotoxin-induced hemodynamic changes in dogs: role of thromboxane and prostaglandin I2.

Plasma concentrations of thromboxane and prostaglandin I2 (PGI2) before and after IV injection of endotoxin and resulting hemodynamic changes were evaluated. Effects of flunixin meglumine on plasma concentrations of these prostaglandins and the related hemodynamic changes were also determined. Shock was induced in 2 groups of anesthetized dogs. Four dogs were given endotoxin only and 4 dogs were given endotoxin and then were treated with flunixin meglumine. Arterial blood pressure (BP), cardiac output (CO), and heart rate were measured, and blood samples were collected at postendotoxin hours (PEH) 0, 0.1, 0.25, 0.5, 1, 2, 3, and 4. Plasma thromboxane and PGI2 concentrations were increased in canine endotoxic shock. Thromboxane concentration was highest early in shock, and appeared to be associated with an initial decrease in BP and CO. The increased concentration of PGI2 was associated with systemic hypotension at PEH 1 to 2. Treatment of dogs with flunixin meglumine at PEH 0.07 prevented further increase of thromboxane and blocked the release of PGI2, resulting in an increased CO, BP, and tissue aerobic metabolism.