THYROID HORMONE AND CARDIAC SURGERY

描述：(改编自申请人的摘要)冠状动脉搭桥术 移植(CABG)是最常见的外科手术之一 美国。在先前的一项关于高危患者接受 在CABG的体外循环中，申请人观察到 甲状腺激素代谢，包括血清三碘甲状腺原氨酸(T3)的下降 降至低于正常水平，这是由T3处理(1.6微克/公斤/6 人力资源)。心房颤动是一种常见的术后并发症。 在46%的未经治疗的患者中观察到。相比之下，只有24 接受T3治疗的患者中发生房颤的百分比(p=0.009) 纤颤。在本申请中，申请人将检验假设 T3通过调节心房肌基因改变心房细胞兴奋性 Na/K-ATPase、Na/Ca交换器和K通道的表达 (包括与房性心律相关的Kv4.2、Kv4.3和IRK1) 骚乱。此外，t3还可以改变 这些单独的离子通道。后一种假设将通过以下方式进行检验 静息膜电位、动作的电生理测量 电位和K电流。模拟冠状动脉旁路移植术的临床情况 心脏停搏液，申请人将研究T3对培养大鼠的影响 心房肌细胞易受低温和高血钾的影响。其次， 冠状动脉致心肌缺血的实验动物模型 结扎，将被用来测试体内T3的抗心律失常作用。至 确定T3的分子作用位点，拍卖者将表达 在非洲爪哇卵母细胞中的单个Kv通道，并研究 这些频道通向T3。最后，申请人建议研究影响 T_3对特异性基因表达、静息膜和动作电位的影响 和冠脉搭桥术时人心房肌细胞的K电流。 这些研究将促进我们对基因表达和 人心房的电生理功能，并鉴定分子 甲状腺激素预防术后房颤的作用机制 心脏手术患者的纤颤。

DESCRIPTION: (Adapted from the applicant's abstract) Coronary artery bypass grafting (CABG) is one of the most commonly performed surgical procedures in the United States. In a prior study of high risk patients undergoing cardiopulmonary bypass for CABG, the applicant observed alterations in thyroid hormone metabolism including a fall in serum triiodothyronine (T3) to levels below normal which was prevented by T3 treatment (1.6 ug/kg/6 hr.). Atrial fibrillation is a common postoperative occurrence and was observed in 46 percent of the untreated patients. In comparison, only 24 percent (p=0.009) of patients receiving T3 treatment developed atrial fibrillation. In this application the applicant will test the hypothesis that T3 can alter atrial cell excitability by modulating atrial gene expression including Na/K-ATPase, Na/Ca exchanger and the K+ channels (including Kv4.2, Kv4.3 and IRK1) that have been linked to atrial rhythm disturbances. In addition, T3 can alter the performance characteristics of these individual ion channels. The latter hypothesis will be tested by electrophysiologic measurements of resting membrane potential, action potential and K+ currents. To model the clinical condition of CABG and cardioplegia, the applicant will study the effects of T3 on cultured rat atrial myocytes subject to hypothermia and hyperkalemia. Secondly, the experimental animal model of myocardial ischemia produced by coronary artery ligation, will be used to test the antiarrhythmic effects of T3 in vivo. To determine the molecular sites of action of T3, the appliant will express the individual Kv channels in the Xenopus oocyte, and study the responses of these channels to T3. Lastly, the applicant proposes to study the effects of T3 on specific gene expression, resting membrane and action potentials, and K+ currents of human atrial myocytes obtained at the time of CABG. These studies will advance our understanding of gene expression and electrophysiologic function of the human atria, and identify the molecular mechanisms by which thyroid hormone acts to prevent postoperative atrial fibrillation in patients undergoing cardiac surgery.