Thyrotropin-releasing hormone increases survival in canine hemorrhagic shock

In our previous work thyroidectomy significantly improved survival in canine hemorrhagic shock. This finding, coupled with the reported beneficial hemodynamic effects of thyrotropin-releasing hormone (TRH) in circulatory collapse, led to the present study. Anesthetized, heparinized dogs were bled rapidly into a reservoir until MAP = 40 mm Hg. After 60 min of hypotension (E60) the reservoir line was clamped for 30 min (E90). In 10 dogs three doses of TRH (2 mg/kg) were administered iv at 10-min intervals during clamping. In 11 other animals equivalent volumes of saline were given. At E90 the reservoir line was unclamped, and shed blood was reinfused over 30 min. After 1 hr of monitoring (E180) the dogs were returned to the kennel and observed for at least 3 days. Among 11 control dogs, 6 died. In the TRH group only 1 of 10 dogs died (P less than 0.05). During uncompensated shock (E60-E90), TRH-treated dogs had significantly higher mean arterial pressure, cardiac index, stroke index, and right and left ventricular stroke work indexes, and arterial pH than control animals. At the conclusion of the acute experiment (E180) there were few intergroup hemodynamic-metabolic differences. The significant enhancement of 3-day survival by TRH in canine hemorrhagic shock might be related to hemodynamic improvement at a critical stage of circulatory collapse (E60-E90). Direct or indirect neuromodulatory actions of TRH on the CNS could also explain our results. These findings lend further support to the potentially key role of hypothalamic-pituitary-thyroid interrelationships in shock.