THYROID HORMONE AND CARDIAC SURGERY

描述：（改编自申请人摘要）冠状动脉搭桥术 冠状动脉旁路移植术（CABG）是最常见的外科手术之一， 美国的 在先前的一项研究中， 在CABG的心肺转流中，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）下降 T3处理（1.6 ug/kg/6）防止了这一现象 （hr.）。房颤是术后常见的并发症， 在46%的未治疗患者中观察到。 相比之下，只有24 %（p=0.009）接受T3治疗的患者发生心房颤动 纤维性颤动 在本申请中，申请人将检验假设 T3可通过调节心房基因改变心房细胞兴奋性 表达包括Na/K-ATP酶、Na/Ca交换器和K+通道 （包括Kv4.2、Kv4.3和IRK 1）与心房节律相关 干扰. 此外，T3可以改变 这些独立的离子通道。 后一个假设将由以下人员进行检验： 静息膜电位、动作的电生理学测量 电位和K+电流。 模拟CABG的临床状况， 心脏停搏液，申请人将研究T3对培养大鼠的影响 心房肌细胞体温过低和血钾过多。 二是 实验性冠状动脉心肌缺血动物模型 连接，将用于测试T3在体内的抗肿瘤作用。 到 确定T3作用的分子位点，申请人将表达T3的分子位点。 单个Kv通道在非洲爪蟾卵母细胞，并研究的反应， 这些通道到T3。 最后，申请人建议研究 T3对特定基因表达、静息膜和动作电位的影响， 和人心房肌细胞的K+电流。 这些研究将促进我们对基因表达的理解， 人心房电生理功能，并确定分子 甲状腺激素预防术后心房颤动的作用机制 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.