Cardiorespiratory alterations produced by centrally administered thyrotropin-releasing hormone during canine endotoxin shock.
Endogenous opiates have been implicated in the pathophysiology of endotoxin, hemorrhagic, and spinal shock. Blockade of these compounds with peripherally or centrally administered naloxone has been shown to produce beneficial effects. More recently, it has been suggested that thyrotropin-releasing hormone (TRH) may be able to block the detrimental effects of endogenous opiate compounds without removing their analgesic effects. Improved cardiovascular function during endotoxin shock has been demonstrated in rat and primate models; however, this drug has not been tested in the canine endotoxin shock model. The present study was designed to determine if TRH administered through ventriculocisternal (VC) perfusion could significantly improve cardiorespiratory function during canine endotoxin shock. Cardiac output, arterial pressure, end-tidal CO2, heart rate, respiratory rate, pulse pressure, and total peripheral resistance were determined for three separate groups of animals. One group of animals received TRH only and served as a drug control. One of the remaining groups received endotoxin only, while the other group received endotoxin plus TRH. The results of the study suggest that TRH administered centrally is capable of improving cardiac output during endotoxin shock. No significant difference was found in any of the other parameters measured. Based on these findings, it can be concluded that TRH has a minimal effect during canine endotoxin shock. The discrepancy between these results and those from other endotoxin shock models may result from species variation, TRH metabolism and sensitivity, and/or anesthetic effect.