THE EFFECT OF THYROID-HORMONE SUPPLEMENTATION ON HEMODYNAMIC STABILITY AND SURVIVAL IN AN ENDOTOXIN-INDUCED MODEL OF PHYSIOLOGICAL STRESS

Severe physiologic stress is associated with intense changes in the sy stemic hormonal milieu. Among these changes are suppression of the thy roid hormone axis resulting in decreased levels of triiodothyronine (T -3) and thyroxine (T-4). This study was conducted to determine whether supplemental T-3 Or T-4 improved (1) hemodynamic stability and/or (2) survival following a standardized level of endotoxin (ET)-induced phy siologic stress. Forty-eight hours after placement of internal jugular vein and carotid artery cannulas, male Sprague-Dawley rats (n = 91) w ere subjected to ET (15 or 20 mg/kg Salmonella enteritidis ET). Follow ing an ET-induced decrease in mean arterial pressure (MAP), the animal s received a continuous infusion of normal saline (NS), T-3 (0.08, 0.4 , or 2.0 mu g/kg/hr), 0.4 mu g/kg/hr T-3 in conjunction with 25 or 50 mu g/min phenylephrine (PE), 0.4 mu g/kg/hr T-3 and 5 mu g/min dopamin e, or 4.0 mu g/kg/hr T-4. There were no statistically significant diff erences in MAP during a 24-hr monitoring period among treatment groups , At 24 hr, there were no statistically significant differences in sur vival among animals treated with T-3 alone (P > 0.05), Treatment with 4.0 mu g/kg/hr T-3 produced a 24-hr survival of 78% (versus 52% NS con trols); however, this was not significant (P > 0.05). Phenylephrine ad ministered in conjunction with T-3 yielded a worse survival when compa red to controls (0% versus 44%, P < 0.05); however, treatment with dop amine and T-3 resulted in no change in survival at 24 hr (25%, P > 0.0 5). Within the dose ranges studied, T-3 alone or in conjunction with d opamine or T-4 alone did not improve hemodynamic stability or survival in an ET-induced model of physiologic stress. T-3 in conjunction with PE resulted in a significantly worse survival after ET. (C) 1996 Acad emic Press, Inc.