Specially for low-frequency variants, with deep coverage.Author ContributionsConceived and designed the experiments: OZ MD CB NB. Performed the experiments: MD CB. Analyzed the data: OZ NB. Contributed reagents/ materials/analysis tools: MD CB. Wrote the paper: OZ NB.
Thyroid hormones (THs) play a pivotal role in regulating cardiac homeostasis as well as the get AKT inhibitor 2 peripheral vascular system in physiologic and pathologic conditions [1,2]. THs influence heart rate (HR), myocardial contractility, total peripheral resistance (TPR), and ultimately cardiac output. At the cellular level, THs enhance myocardial contractility by regulating the expression of Ca2+ handling, myosin heavy chain isoforms (bRa), and potentiating the b-adrenergic system [1,3,4]. THs also exert their influence by regulating non-myocyte cells such as fibroblasts, vascular smooth muscle cells, pericytes, and adipocytes. Excess TH is associated with elevated HR, decreased TPR, 
widened pulse pressure, blood volume expansion, and increased cardiac output [1]. In the short term, hyperthyroidism is associated with heightened left ventricular (LV) contractile function and improved hemodynamic parameters. However, excess TH levels increase tissue metabolic rate, ATP consumption, and heat production, which ultimately leads to increased peripheral oxygenconsumption, inefficient myocardial energy utilization, and increased cardiac work [5?]. The consequences of sustained hyperthyroidism include increased risk of arrhythmias, impaired cardiac reserve and exercise capacity, and myocardial remodeling [8?2]. Longstanding hyperthyroidism leads to cardiac impairment characterized by low cardiac output, Eledoisin biological activity chamber dilation, and “heart failure like” symptoms [13?8]. Interestingly, the dilation and diminished cardiac 18055761 function caused by thyrotoxicosis often is ameliorated or reversed when euthyroidism is re-established. A 
better understanding of the progression and cellular mechanisms responsible for cardiac dysfunction during periods of sustained hyperthyroidism is clinically important. There is limited information within the current literature examining the relationship between myocyte function and global cardiac function during the transition from cardiac compensation to decompensation in the setting of sustained hyperthyroidism. Furthermore, there is limited and conflicting information regarding the functional consequences of increased LV fibrotic deposition in the setting of sustained hyperthyroidism. While previous investiLV Myocyte/Chamber Function in Hyperthyroidismgations have examined the influence of hyperthyroidism on cardiac function either in vivo or in vitro, the relationship between in vivo cardiac function, in vitro isolated myocyte function, and LV fibrosis in this setting is poorly understood. Our lab previously characterized the influence of hyperthyroidism on cardiac remodeling and function during short (10 days) and moderate length (2 months) treatment periods in F1B hamsters [19]. To provide better understanding of the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined global cardiac function, LV isolated myocyte function, and whole tissue remodeling using the previously characterized F1B hamster model. This study suggests that the impairment in overall cardiac function observed with long standing hyperthyroidism is not related to decline in the functional capacity of individual myocytes.LV Hemodynamic MeasurementsPrior to sacrifice, L.Specially for low-frequency variants, with deep coverage.Author ContributionsConceived and designed the experiments: OZ MD CB NB. Performed the experiments: MD CB. Analyzed the data: OZ NB. Contributed reagents/ materials/analysis tools: MD CB. Wrote the paper: OZ NB.
Thyroid hormones (THs) play a pivotal role in regulating cardiac homeostasis as well as the peripheral vascular system in physiologic and pathologic conditions [1,2]. THs influence heart rate (HR), myocardial contractility, total peripheral resistance (TPR), and ultimately cardiac output. At the cellular level, THs enhance myocardial contractility by regulating the expression of Ca2+ handling, myosin heavy chain isoforms (bRa), and potentiating the b-adrenergic system [1,3,4]. THs also exert their influence by regulating non-myocyte cells such as fibroblasts, vascular smooth muscle cells, pericytes, and adipocytes. Excess TH is associated with elevated HR, decreased TPR, widened pulse pressure, blood volume expansion, and increased cardiac output [1]. In the short term, hyperthyroidism is associated with heightened left ventricular (LV) contractile function and improved hemodynamic parameters. However, excess TH levels increase tissue metabolic rate, ATP consumption, and heat production, which ultimately leads to increased peripheral oxygenconsumption, inefficient myocardial energy utilization, and increased cardiac work [5?]. The consequences of sustained hyperthyroidism include increased risk of arrhythmias, impaired cardiac reserve and exercise capacity, and myocardial remodeling [8?2]. Longstanding hyperthyroidism leads to cardiac impairment characterized by low cardiac output, chamber dilation, and “heart failure like” symptoms [13?8]. Interestingly, the dilation and diminished cardiac 18055761 function caused by thyrotoxicosis often is ameliorated or reversed when euthyroidism is re-established. A better understanding of the progression and cellular mechanisms responsible for cardiac dysfunction during periods of sustained hyperthyroidism is clinically important. There is limited information within the current literature examining the relationship between myocyte function and global cardiac function during the transition from cardiac compensation to decompensation in the setting of sustained hyperthyroidism. Furthermore, there is limited and conflicting information regarding the functional consequences of increased LV fibrotic deposition in the setting of sustained hyperthyroidism. While previous investiLV Myocyte/Chamber Function in Hyperthyroidismgations have examined the influence of hyperthyroidism on cardiac function either in vivo or in vitro, the relationship between in vivo cardiac function, in vitro isolated myocyte function, and LV fibrosis in this setting is poorly understood. Our lab previously characterized the influence of hyperthyroidism on cardiac remodeling and function during short (10 days) and moderate length (2 months) treatment periods in F1B hamsters [19]. To provide better understanding of the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined global cardiac function, LV isolated myocyte function, and whole tissue remodeling using the previously characterized F1B hamster model. This study suggests that the impairment in overall cardiac function observed with long standing hyperthyroidism is not related to decline in the functional capacity of individual myocytes.LV Hemodynamic MeasurementsPrior to sacrifice, L.