Whitesall S E, Mayor G H, Nachreiner R F, Zwemer C F, D'Alecy L G
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Resuscitation. 1996 Nov;33(1):53-62. 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.
与心脏骤停及复苏以及其他急性紧急情况相关的血清甲状腺激素浓度的显著变化记录，促使人们对甲状腺激素治疗给药的可能性进行评估。这种以血清甲状腺激素浓度异常降低为特征的急性且显著的状态，可能提示选择性甲状腺替代治疗。在先前的一项研究中，复苏后输注左甲状腺素钠（L-T4）以使血清3,5,3'-三碘甲状腺原氨酸（T3）浓度正常化，与严重全脑缺血所致神经功能缺损的显著减轻相关。由于据报道L-T4直接发挥作用或通过其一种代谢产物（很可能是T3）发挥作用，因此对这种甲状腺激素的最活跃形式进行了测试。当L-T4减轻神经功能缺损时，还观察到3,3',5'-三碘甲状腺原氨酸（反T3，rT3）增加。因此，本研究确定复苏后用T3（n = 8）或rT3（n = 8）治疗是否能提供与L-T4相当的针对全脑缺血的保护作用。通过9分钟的心室颤动实现全脑缺血。复苏后，以能重现先前L-T4治疗期间达到的正常血清T3浓度或rT3浓度的速率输注三种溶液之一（生理盐水组作为对照），持续24小时。通过放射免疫分析（RIA）评估并确认了T3和模拟rT3浓度的成功升高。此外，用一种针对犬促甲状腺激素（cTSH）的新型RIA测量促甲状腺激素（TSH）水平。用标准化良好的神经功能缺损检查评估神经功能缺损。与先前使用L-T4输注的研究不同，未观察到神经功能缺损有显著减轻。血清甲状腺激素变化证实了先前描述的降低情况，并且在任何情况下促甲状腺激素变化似乎都不是这些变化的原因。因此，我们得出结论，L-T4可能比T3或rT3具有治疗优势。
