Lack of effect of thyrotropin releasing hormone (TRH) in circulatory shock.
Thyrotropin releasing hormone (TRH) has been reported to reverse hypotension induced by a variety of agents and thus it has been suggested to be of therapeutic value in circulatory shock. We have investigated TRH (2 mg/kg bolus plus 2 mg/kg/hr infusion) in both hemorrhagic (cats) and traumatic shock (rats). TRH induced a pressor effect of 23 +/- 8 mm Hg (p less than 0.05) in cats and 19 +/- 3 mm Hg (p less than 0.01) in rats during hypotension. However, this transient (10-15 min) response did not result in any sustained improvement in the cardiovascular status of the animals in either shock model when compared to the vehicle. In addition, TRH did not attenuate any of the biochemical indices of the severity of the shock state (i.e., plasma amino-nitrogen concentrations, or plasma cathepsin D and MDF activities) nor did it improve survival time in traumatic shock (2.8 +/- 0.4 vs. 2.0 +/- 0.2 hours). Furthermore, TRH resulted in a significant blunting of the maximum post-reinfusion superior mesenteric artery flow and enhanced beta-glucuronidase release from liver lysosomal preparations in vitro. These potentially detrimental effects in conjunction with the lack of any overt protective effect under the conditions existing in these two shock models, do not provide evidence that TRH is beneficial as a therapeutic agent in circulatory shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002415:Cats; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012769:Shock / Q000188:drug therapy*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013152:Splanchnic Circulation / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000627:therapeutic use*
D001798:Blood Proteins; D009201:Myocardial Depressant Factor; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital