Schmidt Bernhard M W, Martin Nicole, Georgens Anette C, Tillmann Hanns-C, Feuring Martin, Christ Michael, Wehling Martin
Institute of Clinical Pharmacology, University Hospital of Mannheim, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
J Clin Endocrinol Metab. 2002 Apr;87(4):1681-6. doi: 10.1210/jcem.87.4.8410.
T(3) has been shown to exert cardiovascular effects. These effects have not yet been defined with regard to the mode of action (nongenomic vs. genomic) and with regard to an interaction with the adrenergic system in humans. To address these issues we conducted a randomized, double blind, 6-fold cross-over trial in 18 healthy male volunteers. After pretreatment with the beta-agonist dobutamine, the beta-blocking agent esmolol, or placebo (0.9% NaCl), 100 microg T(3) or placebo were injected. Primary target variables were systemic vascular resistance (SVR) and cardiac output (CO) within 45 min after injection of T(3) vs. placebo after placebo pretreatment. Sympatho-vagal balance was assessed by measurement of heart rate variability. T(3) caused a lower SVR and a higher CO than placebo (P < 0.001) after pretreatment with placebo. An increased low frequency (LF)/high frequency (HF) ratio (power in LF/power in HF band) after T(3) compared with placebo (P = 0.004) suggests an increase in sympathetic tone. After pretreatment with dobutamine, the effects of T(3) on SVR and CO were abolished, and the effect on LF/HF ratio was reversed. After pretreatment with esmolol, the effects on SVR and LF/HF ratio were reversed. Our data show, for the first time, nongenomic cardiovascular effects of T(3) in humans.
已证实T(3)具有心血管效应。但这些效应在作用方式（非基因组与基因组）以及与人类肾上腺素能系统的相互作用方面尚未明确。为解决这些问题，我们对18名健康男性志愿者进行了一项随机、双盲、6次交叉试验。在用β-激动剂多巴酚丁胺、β-阻滞剂艾司洛尔或安慰剂（0.9%氯化钠）预处理后，注射100微克T(3)或安慰剂。主要目标变量是在安慰剂预处理后注射T(3)与安慰剂后45分钟内的全身血管阻力（SVR）和心输出量（CO）。通过测量心率变异性评估交感-迷走平衡。在安慰剂预处理后，T(3)导致的SVR低于安慰剂，CO高于安慰剂（P<0.001）。与安慰剂相比，T(3)后低频（LF）/高频（HF）比值增加（LF频段功率/HF频段功率）（P = 0.004），提示交感神经张力增加。在用多巴酚丁胺预处理后，T(3)对SVR和CO的作用被消除，对LF/HF比值的作用被逆转。在用艾司洛尔预处理后，对SVR和LF/HF比值的作用被逆转。我们的数据首次显示了T(3)在人类中的非基因组心血管效应。
