Acute administration of T3 or rT3 failed to improve outcome following resuscitation from cardiac arrest in dogs

• Published in: Resuscitation 1996-11, Vol.33 (1), p.53-62
• Main Authors: Whitesall, Steven E., Mayor, Gilbert H., Nachreiner, Ray F., Zwemer, Charles F., D'Alecy, Louis G.
• Format: Article
• Language: English
• Subjects: Animals; Brain Ischemia - prevention & control; Dogs; Global cerebral ischemia; Heart Arrest - therapy; Levothyroxine sodium; Low serum thyroid hormone concentration; Male; Neurologic deficit; Neurologic Examination; Radioimmunoassay; Resuscitation; Reverse triiodothyronine; Thyroxine - therapeutic use; Time Factors; Triiodothyronine; Triiodothyronine - therapeutic use; Triiodothyronine, Reverse - therapeutic use
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/S0300-9572(96)00985-9

Documentation of profound changes in serum thyroid hormone concentrations associated with cardiac arrest and resuscitation, as well as other acute emergencies, have spurred evaluation of possible therapeutic thyroid hormone administration. Acute and significant, this state, characterized by abnormally low serum thyroid hormone concentrations, may indicate selective thyroid replacement therapy. In a previous investigation, post-resuscitation infusion of levothyroxine sodium (L-T4) to normalize serum 3,5,3′-triiodothyronine (T3) concentrations was associated with significant reduction of neurologic deficit caused by severe global cerebral ischemia. Since L-T4 has been reported to act directly or via one of its metabolites, most likely T3, this most active form of thyroid hormone was tested. When L-T4 reduced the neurologic deficit, an increase in 3,3′,5′-triiodothyronine (rT3) was also observed. This study therefore determined whether a post-resuscitation treatment with either T3 ( n = 8) or rT3 ( n = 8) provided protection against global cerebral ischemia comparable to that of L-T4. Global cerebral ischemia was achieved with 9 min of ventricular fibrillation. Following resuscitation, one of three solutions (saline group as a control) was infused for 24 h at rates that reproduced the normal serum T3 concentrations or the rT3 concentrations achieved previously during the L-T4 therapy. The successful elevation of T3 and mimicking rT3 concentrations was assessed and confirmed by radioimmunoassay (RIA). In addition, TSH levels were measured by a novel RIA specific for canine thyroid-stimulating hormone (cTSH). Neurologic deficit was assessed with a well-standardized neurologic deficit examination. In contrast to previous studies using L-T4 infusion, no significant reduction of neurologic deficit was observed. Serum thyroid hormone changes confirmed previously described decreases and in no case did changes in cTSH appear causal in these changes. Thus, we concluded that L-T4 may offer a therapeutic advantage over T3 or rT3.