Thyroid acting through ligand binding to nuclear receptors modifies myocardial respiratory kinetics and oxidative phosphorylation in the heart. Direct nongenomic action of thyroid hormone on high-energy phosphate concentrations and respiratory kinetics has never been proven in vivo but might be responsible for observed changes in oxygen utilization efficiency immediately after triiodothyronine (T3) administration. We tested the hypothesis that T3directly and rapidly modifies myocardial high-energy phosphate concentrations and phosphorylation potential in vivo. Anesthetized sheep (age 28–40 days) thyroidectomized shortly after birth (Thy) and euthyroid age-matched controls (Con) underwent median sternotomy and received T3infusion (0.8 μg/kg), followed by epinephrine infusion to increase myocardial oxygen consumption (MV̇o2).31P magnetic resonance spectra were monitored via a surface coil over the left ventricle. T3increased phosphocreatine (PCr)/ATP and decreased ADP in Thy animals without causing a change in MV̇o2. T3produced no changes in high-energy phosphates in Con animals. T3did not modify the PCr/ATP or ADP response to epinephrine and elevation in MV̇o2in either group. Cardiac mitochondria isolated from Thy and Con animals showed no change in respiratory rate or ADP/ATP exchange efficiency after T3incubation. T3infusion in a hypothyroid state decreases ADP concentration, thereby altering the equilibrium between phosphorylation potential and myocardial respiratory rate. These T3-induced effects are not due to changes in ADP/ATP exchange efficiency through action at the adenine nucleotide translocator but may be due to T3mediation of substrate utilization, confirmed in other models.

How T3 hormone fixes a tired heart in sick sheep

Direct action of T3 on phosphorylation potential in the sheep heart in vivo.

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