Abstract 3158: Depressed Contractile Reserve and Impaired Calcium Handling of Cardiac Myocytes From Chronically Unloaded Heart Are Ameliorated With Low Dose of Thyroid Hormone in Rats
Introduction: Left ventricular assist devices (LVADs) are used to treat patients with severe heart failure. However, LVAD-induced cardiac unloading with subsequent cardiac atrophy might limit the potential benefits of the LVAD support. We have previously demonstrated that chronic cardiac unloading causes a time-dependent depression of myocyte contractility and upregulation of phospholamban in normal rat hearts.
Hypothesis: Since thyroid hormone is known to increase phospholamban expression, we assessed the hypothesis that thyroid hormone restores depressed contractile performance in chronically unloaded normal hearts.
Methods: Cardiac unloading was induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats for 5 weeks. Animals were treated with either vehicle or a low-dose of 3,5,3’-triiodo-L-thyronine (T3) that dose not cause hyperthyroidism using an osmotic pump for the last 3 weeks (n=20 each).
Results: In vehicle-treated animals, myocyte relaxation and [Ca2+]i decay were slower in unloaded hearts than in recipient hearts. Contractile reserve of myocytes in response to high [Ca2+]o was also depressed with impaired augmentation of peak-systolic [Ca2+]i in unloaded hearts compared with recipient hearts. Also, in vehicle-treated rats, protein levels of phospholamban in LV from unloaded hearts were increased (236% of recipient heart values) and the levels of phosphorylation of phospholamban at Ser16 were lower in unloaded hearts than in recipient hearts. On the other hand, in the T3-treated animals, the slower relaxation, delayed [Ca2+]i decay, and the depressed contractile reserve in unloaded hearts were all returned to normal levels. Furthermore, in the T3-treated animals, there were no differences in phospholamban protein levels or its phosphorylation at Ser16 between unloaded and recipient hearts.
Conclusions: These results indicate that the treatment with a low-dose of thyroid hormone rescues the depressed contractile reserves through restoration of phospholamban protein levels and its phosphorylation state in chronically unloaded normal hearts. These findings may have clinical implications for patients undergoing prolonged and extreme cardiac unloading in patients with LVAD.