Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

Abstract

Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day), on thyroxine (T4; 500 µg/kg/day)-induced increase in blood pressure (BP), cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV) function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV) contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

Biologically-Guided Isolation of Natural Lead Antithyroid Drug from Medicago sativa L. Sprouts and Its Toxic Profile in Comparison with Propylthiouracil

“…Since there was no significant difference in mean serum T3 level between apigenin and PTU-treated groups, other molecular mechanisms may contribute to the dissimilar results of both therapies on hyperthyroidism-induced LVH that need extra investigations. Consistent with our results regarding PTU therapy, common cardiovascular abnormalities accompanying hyperthyroidism persisted despite effective PTU antithyroid therapy in L-thyroxine induced hyperthyroidism in FVB/N male mice [69], in rats [70] and in patients with overt hyperthyroidism [71]. Concerning the effect of PTU on cardiac fibrosis, there is a common agreement on the association of hypothyroidism and cardiac fibrosis [67,72].…”

Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside

“…And they reported that these aforementioned patients could also have their cardiac function completely restored after total thyroidectomy ( Muthukumar et al, 2016 ). In fact, Saad et al have reported that treatment of the thyroid gland significantly prevented cardiac dysfunction in a mouse model of T4-induced cardiac dysfunction ( Saad et al, 2017 ). Furthermore, reversibility of heart disease was observed after 2 weeks of T4 treatment, including cardiac hypertrophy ( Saad et al, 2017 ).…”

“…In fact, Saad et al have reported that treatment of the thyroid gland significantly prevented cardiac dysfunction in a mouse model of T4-induced cardiac dysfunction ( Saad et al, 2017 ). Furthermore, reversibility of heart disease was observed after 2 weeks of T4 treatment, including cardiac hypertrophy ( Saad et al, 2017 ).…”

Impact of hyperthyroidism on cardiac hypertrophy

“…Supporting clinical findings, experimental data also demonstrated that antithyroid treatment significantly prevented the cardiac dysfunction induced by T4 in mice. In addition, the reversibility of cardiac pathology was also observed after 2 weeks of discontinuation of treatment with T4, including cardiac hypertrophy (53).…”