Restoration Of Serum Euthyroidism Is Inadequate To Reverse Cardiac Dysfunction In Experimental Hypothyroidism

Clinical observations suggest a strong link between hypothyroidism (H) and poor outcomes in heart disease. We evaluated the efficacy of 2 weeks of Triiodothyronine (T 3 ) in drinking water administered to hypothyroid rats with cardiac dysfunction to characterize the dosage of T 3 that restores serum TH levels and cardiac function in propylthiouracil (PTU) induced H. PTU treatment reduced serum THs, small resistance vessels, and caused cardiac atrophy and LV dysfunction. PTU led to increased wall stress, primarily owing to a relative decrease in LV posterior wall thickness. Treatment with 3μg/kg/day restored serum TH levels while 5μg/kg/day reversed cardiac atrophy and wall thinning. A significant elevation in serum THs was necessary for complete LV functional restoration. LV Function HR LV ESP dP/dT −dP/dT LV FS Control 366 (48) 142 (14) 10790 (2499) −11910 (2299) 41 (5) PTU 229 (38) * 105 (12) * 4209 (626) * −4266 (891) * 35 (3) * PTU + 3 T3 270 (27) * † 107 (13) * 5366 (718) * −5623 (1120) * 36 (6) PTU + 5 T3 313 (27) * † 113 (10) * 6223 (845) * −6399 (999) * 38 (4) PTU + 10 T3 363 (47) † 139 (21) † 9380 (1890) † −11097 (3075) † 42 (4) † p<.05 vs Control; p<.05 vs PTU In PTU induced H, restoration of serum THs was not associated with restoration of cardiac function suggesting that serum TH levels might not accurately reflect cardiac TH status. Short term T 3 dosing to restore serum THs is inadequate to fully reverse cardiac dysfunction in PTU induced H.