Kuzman James A, Thomas Tracy A, Vogelsang Kathryn A, Said Suleman, Anderson Brent E, Gerdes A Martin
Cardiovascular Research Institute, South Dakota Health Research Foundation, University of South Dakota, Sioux Falls, 57105, USA.
J Appl Physiol (1985). 2005 Oct;99(4):1428-33. doi: 10.1152/japplphysiol.00515.2005. Epub 2005 Jun 23.
Thyroid hormones (TH) enhance cardiac function and reverse gene changes typical of pathological hypertrophy. However, reports in humans, but not animals, indicate that excess TH can cause heart failure. Also, the effects of TH on normal and cardiomyopathic hearts are likely to be different. The goal of this study was to characterize the effects of prolonged hyperthyroidism on cardiac function, chamber and cellular remodeling, and protein expression in both normal and cardiomyopathic hearts. Hyperthyroidism was induced in 3-mo-old normal BIO F1B and dilated cardiomyopathic BIO TO2 hamsters. After TH treatment for 10 days and 2 mo, hemodynamics, echos, myocyte length, histology, and protein expression were assessed. After 10 days and 2 mo, there were no differences between TO2-treated (Tx) and TO2-untreated (Untx) hamsters in chamber diameters or left ventricular function. After 2 mo of treatment, however, F1B-Tx showed evidence of dilated heart failure vs. F1B-Untx. Chamber diameters were increased, and ejection fraction and positive and negative changes in pressure over time were reduced. In F1B-Tx and TO2-Tx hamsters, beta-myosin isoform expression was reduced, whereas alpha-myosin increased significantly in F1B-Tx only. In TO2-Tx hamsters, the percent of viable myocardium was increased, and percent fibronecrosis was reduced vs. TO2-Untx. Myocyte length increased with TH treatment in both hamster strains. We conclude that 1) excess TH can induce heart failure in normal animals as observed in humans, 2) reversal of myosin heavy chain expression does not necessarily improve heart function, and 3) excess TH altered cellular remodeling but did not adversely affect chamber function or dimensions in TO2 hamsters.
甲状腺激素（TH）可增强心脏功能，并逆转病理性肥大典型的基因变化。然而，人类研究报告（而非动物研究报告）表明，过量的TH可导致心力衰竭。此外，TH对正常心脏和心肌病心脏的影响可能不同。本研究的目的是明确长期甲状腺功能亢进对正常心脏和心肌病心脏的心脏功能、心室及细胞重塑以及蛋白质表达的影响。对3月龄正常的BIO F1B和扩张型心肌病BIO TO2仓鼠诱导甲状腺功能亢进。在TH治疗10天和2个月后，评估血流动力学、超声心动图、心肌细胞长度、组织学和蛋白质表达。10天和2个月后，接受治疗的TO2（Tx）仓鼠和未接受治疗的TO2（Untx）仓鼠在心室直径或左心室功能方面没有差异。然而，治疗2个月后，F1B-Tx仓鼠出现扩张型心力衰竭的迹象，而F1B-Untx仓鼠则未出现。心室直径增加，射血分数以及压力随时间的正负变化均降低。在F1B-Tx和TO2-Tx仓鼠中，β-肌球蛋白同工型表达降低，而仅在F1B-Tx仓鼠中α-肌球蛋白显著增加。与TO2-Untx仓鼠相比，TO2-Tx仓鼠存活心肌百分比增加，纤维坏死百分比降低。两种仓鼠品系的心肌细胞长度均随TH治疗而增加。我们得出以下结论：1）如在人类中观察到的那样，过量的TH可在正常动物中诱发心力衰竭；2）肌球蛋白重链表达的逆转不一定能改善心脏功能；3）过量的TH改变了细胞重塑，但对TO2仓鼠的心室功能或尺寸没有不利影响。
