The effect of indomethacin and adrenergic receptor blocking agents on rats and canine responses to endotoxin

The effect of indomethacin, a prostaglandin (PG) synthesis inhibitor, on the hemodynamics and survival rates of Escherichia coli endotoxin-administered animals (dog and Rat) was studied. Indomethacin post-treatment significantly elevated aortic pressure, cardiac output, and left ventricular isometric tension elevated aortic pressure, cardiac output, and left ventricular isometric tension rise (LVP dp/dt max) following endotoxin administration in the dog. In dogs in a hyperdynamic state due to indomethacin administration treated with phenoxybenzamine (COB) and alprenolol, aortic pressure and cardiac output fell to pre-indomethacin administration values. In reserpine-administered and bilaterally adrenalectomized dogs, hemodynamic states were not altered by indomethacin administration during endotoxin shock. These results suggest that indomethacin potentiates the responses of catecholamines induced by endotoxin shock. Pretreatment with indomethacin alone did not increase the survival rates in endotoxin-administered rats. However, pretreatment and posttreatment with indomethacin combined with POB significantly increased the survival rate over untreated controls (LD 80) given endotoxin alone. Cyclic adenosine monophosphate (cAMP) levels in liver tissue decreased significantly in untreated controls and rats pretreated with indomethacin alone. In contrast, tissue cAMP levels remained within normal values in rats pretreated with indomethacin combined with POB. These results indicate that indomethacin may make a significant contribution as an antishock agent when peripheral circulation is maintained.