The effect of thyroid hormone supplementation on hemodynamic stability and survival in an endotoxin-induced model of physiologic stress.
Severe physiologic stress is associated with intense changes in the systemic hormonal milieu. Among these changes are suppression of the thyroid hormone axis resulting in decreased levels of triiodothyronine (T3) and thyroxine (T4). This study was conducted to determine whether supplemental T3 or T4 improved (1) hemodynamic stability and/or (2) survival following a standardized level of endotoxin (ET)-induced physiologic stress. Forty-eight hours after placement of internal jugular vein and carotid artery cannulas, male Sprague-Dawley rats (n = 91) were subjected to ET (15 or 20 mg/kg Salmonella enteritidis ET). Following an ET-induced decrease in mean arterial pressure (MAP), the animals received a continuous infusion of normal saline (NS), T3 (0.08, 0.4, or 2.0 micrograms/kg/hr), 0.4 microgram/kg/hr T3 in conjunction with 25 or 50 micrograms/min phenylephrine (PE), 0.4 microgram/kg/hr T3 and 5 micrograms/min dopamine, or 4.0 micrograms/kg/hr T4. There were no statistically significant differences in MAP during a 24-hr monitoring period among treatment groups. At 24 hr, there were no statistically significant differences in survival among animals treated with T3 alone (P > 0.05). Treatment with 4.0 micrograms/kg/hr T4 produced a 24-hr survival of 78% (versus 52% NS controls); however, this was not significant (P > 0.05). Phenylephrine administered in conjunction with T3 yielded a worse survival when compared to controls (0% versus 44%, P < 0.05); however, treatment with dopamine and T3 resulted in no change in survival at 24 hr (25%, P > 0.05). Within the dose ranges studied, T3 alone or in conjunction with dopamine or T4 alone did not improve hemodynamic stability or survival in an ET-induced model of physiologic stress. T3 in conjunction with PE resulted in a significantly worse survival after ET.
Glembot
T M
TM
Department of General Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.
Hill
M A
MA
Britt
L D
LD
D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D005740:Gases / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology*; D016019:Survival Analysis; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D004731:Endotoxins; D005740:Gases; D014284:Triiodothyronine; D013974:Thyroxine