Hoit B D, Khoury S F, Shao Y, Gabel M, Liggett S B, Walsh R A
Division of Cardiology, University of Cincinnati Medical Center, Ohio 45267-0542, USA.
Circulation. 1997 Jul 15;96(2):592-8. doi: 10.1161/01.cir.96.2.592.
Many of the cardiovascular manifestations of thyroid hormone excess resemble those produced by sympathoadrenal stimulation. The objective of this study was to determine the effects of thyroid hormone excess on myocardial beta-adrenergic expression and responsiveness to infused agonists in the primate heart.
The responses of left ventricular isovolumic contraction (dP/dt(max)) and relaxation (tau) during graded dobutamine infusion were studied both before and after 4 weeks of thyroid hormone administration in 8 chronically instrumented baboons. At matched (atrially paced) heart rates, thyroid hormone significantly increased resting dP/dt(max) (3073+/-1034 versus 2318+/-829 mm Hg/s, P<.05) and decreased tau (24.0+/-5.5 versus 28.2+/-5.4 ms, P<.05). The change from baseline for dP/dt(max) and tau in response to beta1-adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 microg x kg(-1) x min(-1)), but when expressed as a percent change, it was similar before versus after thyroid hormone. Similar changes were found when beta2-adrenergic stimulation was produced by terbutaline infusion in three additional baboons. beta-Adrenergic receptor (betaAR) expression was higher in five thyroxine-treated than in five control baboons (37.4+/-1.2 versus 15.7+/-3.2 fmol/mg, P<.001), and this was due to a greater increase in the beta2AR (5.9+/-1.5 to 20.6+/-1.2 fmol/mg, P<.001) than the beta1AR (9.7+/-1.7 to 16.8+/-0.1 fmol/mg, P<.01) subtype.
In the primate heart, thyroid hormone produces positive inotropic and lusitropic effects in the resting state and upregulates both beta1AR and beta2AR, with the beta2AR increase predominating. At equivalent rates, however, thyroid hormone excess does not appear to enhance the sensitivity of left ventricular contractility and relaxation to either beta1- or beta2-adrenergic stimulation.
甲状腺激素过多引起的许多心血管表现类似于交感肾上腺系统兴奋所产生的表现。本研究的目的是确定甲状腺激素过多对灵长类动物心脏心肌β-肾上腺素能表达及对注入激动剂反应性的影响。
对8只长期植入仪器的狒狒在给予甲状腺激素4周前后，研究了分级输注多巴酚丁胺期间左心室等容收缩（最大dp/dt）和舒张（τ）的反应。在匹配（心房起搏）心率下，甲状腺激素显著增加静息最大dp/dt（3073±1034对2318±829mmHg/s，P<0.05）并降低τ（24.0±5.5对28.2±5.4ms，P<0.05）。在每个多巴酚丁胺剂量（2.5至10μg·kg⁻¹·min⁻¹）下，β1-肾上腺素能刺激引起的最大dp/dt和τ相对于基线的变化均显著，但以百分比变化表示时，甲状腺激素前后相似。在另外3只狒狒中，静脉输注特布他林产生β2-肾上腺素能刺激时也发现了类似变化。5只经甲状腺素治疗的狒狒的β-肾上腺素能受体（βAR）表达高于5只对照狒狒（37.4±1.2对15.7±3.2fmol/mg，P<0.001），这是由于β2AR（5.9±1.5至20.6±1.2fmol/mg，P<0.001）的增加大于β1AR（9.7±1.7至16.8±0.1fmol/mg，P<0.01）亚型。
在灵长类动物心脏中，甲状腺激素在静息状态下产生正性变力和变时作用，并上调β1AR和β2AR，以β2AR增加为主。然而，在相同心率下，甲状腺激素过多似乎并未增强左心室收缩性和舒张性对β1-或β2-肾上腺素能刺激的敏感性。
