The heart is subjected to chronic mechanical unloading during prolonged spaceflight and microgravity. The heart in patients with end-stage heart failure is also unloaded in prolonged duration after left ventricular assist devices (LVAD) are implanted. Heterotopic heart transplantation in rats is an established model of chronic cardiac unloading, and has been used to investigate the effects of chronic cardiac unloading on the heart. Observations that have been found using this experimental model are as follow. Chronic cardiac unloading induces time-dependent depressions of Ca2+ handling and myocyte contractility, which are associated with the shift of myosin heavy chain (MHC) isozymes and altered expressions of Ca2+ cycling-related proteins. Treatment with the physiological treatment dose of thyroid hormone restores the expression levels of Ca2+ cycling-related proteins, Ca2+ handling, and contractile function of cardiac myocytes in chronically unloaded hearts. Although future studies are required to determine precise mechanisms of the beneficial effects of thyroid hormone on chronically unloaded hearts, these observations may have clinical implications in the future for chronic cardiac unloading in the space industry as well as in the treatment of patients with end-stage heart failure supported by LVAD.
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