Hypothyroid heart displays a phenotype of cardioprotection against ischemia and 
this study investigated whether administration of dronedarone, an 
amiodarone-like compound that has been shown to preferentially antagonize 
thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results 
in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily 
(od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). 
Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated 
rat hearts were perfused in Langendorff mode and subjected to 20 minutes of 
zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' 
Triiodothyronine remained unchanged while body weight and food intake were 
reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while 
beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine 
triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, 
alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial 
glycogen content was increased in both DRON and HYPO. In DRON, resting heart 
rate and contractility were reduced and ischemic contracture was significantly 
suppressed while postischemic left ventricular end-diastolic pressure and 
lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. 
In conclusion, dronedarone treatment results in cardioprotection by selectively 
mimicking hypothyroidism. This is accompanied by a reduction in body weight 
because of the suppression of food intake. TRs might prove novel pharmacologic 
targets for the treatment of cardiovascular illnesses.