PURPOSE: It is well known that hyperthyroidism is associated with atrial fibrillation (AF); however, the relationship between hypothyroidism and AF remains controversial. METHODS: Hypothyroidism was established in rats by two methods: methimazole-induced (MMI) and thyroidectomy (TX). MMI model includes control (n = 10), MMI (n = 10), and MMI + L-thyroxine (T4, n = 10). Methimazole was given intragastrically in MMI and MMI + T4 for 12 weeks, and T4 was added intragastrically in MMI + T4 at week 5. TX model includes sham (n = 10), TX (n = 10), and TX + T4 (n = 10). Four weeks after surgery, rats in TX + T4 received T4 for 8 weeks. Triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) were measured. Electrophysiology, tissue structure and function, and protein levels of potassium and L-type calcium channels were assessed in the atria. RESULTS: Severe changes in the atrial structure of hypothyroid rats were observed. Compared with euthyroid rats, atrial effective refractory period (AERP) in hypothyroid rats was significantly shortened; accordingly, inducibility and duration of AF were considerably increased. Protein levels of minK, Kv1.5, Kv4.2, Kv4.3, Kv7.1, and Cav1.2 were upregulated in hypothyroid rats, whereas there was only a tendency toward increased Kir2.1. Kv11.1 was statistically upregulated in the MMI model and had an increasing tendency in the TX model. Conversely, Kir3.1 and Kir3.4 were downregulated in hypothyroid rats. The above changes could be partially inhibited by T4 treatment. CONCLUSIONS: AERP shortening due to altered protein levels of ion channels and atrial structural changes increased the susceptibility to AF in hypothyroidism. Thyroid replacement therapy could prevent electrical and structural remodeling under hypothyroid condition.
PURPOSE: It is well known that hyperthyroidism is associated with atrial fibrillation (AF); however, the relationship between hypothyroidism and AF remains controversial. METHODS:Hypothyroidism was established in rats by two methods: methimazole-induced (MMI) and thyroidectomy (TX). MMI model includes control (n = 10), MMI (n = 10), and MMI + L-thyroxine (T4, n = 10). Methimazole was given intragastrically in MMI and MMI + T4 for 12 weeks, and T4 was added intragastrically in MMI + T4 at week 5. TX model includes sham (n = 10), TX (n = 10), and TX + T4 (n = 10). Four weeks after surgery, rats in TX + T4 received T4 for 8 weeks. Triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) were measured. Electrophysiology, tissue structure and function, and protein levels of potassium and L-type calcium channels were assessed in the atria. RESULTS: Severe changes in the atrial structure of hypothyroidrats were observed. Compared with euthyroid rats, atrial effective refractory period (AERP) in hypothyroidrats was significantly shortened; accordingly, inducibility and duration of AF were considerably increased. Protein levels of minK, Kv1.5, Kv4.2, Kv4.3, Kv7.1, and Cav1.2 were upregulated in hypothyroidrats, whereas there was only a tendency toward increased Kir2.1. Kv11.1 was statistically upregulated in the MMI model and had an increasing tendency in the TX model. Conversely, Kir3.1 and Kir3.4 were downregulated in hypothyroidrats. The above changes could be partially inhibited by T4 treatment. CONCLUSIONS: AERP shortening due to altered protein levels of ion channels and atrial structural changes increased the susceptibility to AF in hypothyroidism. Thyroid replacement therapy could prevent electrical and structural remodeling under hypothyroid condition.
Entities:
Keywords:
Atrial fibrillation; Electrical remodeling; Hypothyroidism; Ion channel; Structural remodeling
Authors: Nassir F Marrouche; David Wilber; Gerhard Hindricks; Pierre Jais; Nazem Akoum; Francis Marchlinski; Eugene Kholmovski; Nathan Burgon; Nan Hu; Lluis Mont; Thomas Deneke; Mattias Duytschaever; Thomas Neumann; Moussa Mansour; Christian Mahnkopf; Bengt Herweg; Emile Daoud; Erik Wissner; Paul Bansmann; Johannes Brachmann Journal: JAMA Date: 2014-02-05 Impact factor: 56.272