Thyrotropin releasing hormone: effects in monkeys and dogs subjected to experimental circulatory shock.
We tested the hypothesis that thyrotropin releasing hormone (TRH) would improve cardiovascular function and survival in circulatory shock by opposing the adverse effects of endogenous opioids and other pathophysiologic mediators. Cynomolgus monkeys and mongrel dogs were anesthetized and catheterized to measure mean arterial pressure (MAP) and left ventricular contractility (LV dp/dtmax). Hemorrhagic shock was induced by bleeding into a reservoir to achieve and maintain MAP at 45 mm Hg for one hour. Endotoxic shock was produced by the iv injection of an LD80 dose of Escherichia coli lipopolysaccharide endotoxin (3 mg/kg in dogs and 5 mg/kg in monkeys). Animals were treated iv with either TRH (2 mg/kg plus 2 mg/kg X h) or equivolume saline. TRH significantly increased MAP and LV dp/dtmax in primate hemorrhagic and endotoxic shock. In primate hemorrhagic shock, TRH significantly (p = .02) improved survival (alive/total = 4/5 vs. 0/5). However, TRH had no effect on survival in endotoxemic primates. In contrast, TRH treatment in dogs produced only a transient hemodynamic response after endotoxemia and no significant hemodynamic effect after acute hemorrhage (even at twice the TRH dose). TRH did not affect survival in either dog model of circulatory shock. Based on extensive evidence with the opiate receptor antagonist naloxone in other studies, endogenous opioids play a role in the cardiovascular depression in primate and canine circulatory shock. From these studies with TRH, we conclude that TRH is relatively ineffective in canine circulatory shock, and physiologic antagonism of the adverse effects of opioids and other cardiodepressant substances by TRH administration may prove to be a useful alternative treatment of primate hemorrhagic shock.
D000818:Animals; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy*; D013045:Species Specificity; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000627:therapeutic use*
D013973:Thyrotropin-Releasing Hormone