TY - JOUR
TI - Dronedarone administration prevents body weight gain and increases
tolerance of the heart to ischemic stress: A possible involvement of
thyroid hormone receptor alpha(1)
AU - Pantos, C
AU - Mourouzis, I
AU - Malliopoulou, V
AU - Paizis, I
AU - Tzeis,
AU - S
AU - Moraitis, P
AU - Sfakianoudis, K
AU - Varonos, DD
AU - Cokkinos, DV
JO - Thyroid Research
PY - 2005
VL - 15
TODO - 1
SP - 16-23
PB - MARY ANN LIEBERT INC PUBL
SN - 1756-6614
TODO - 10.1089/thy.2005.15.16
TODO - null
TODO - 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 alpha(1) (TRalpha(1)), 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.
ER -