Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart.
The present study investigated the effects of dronedarone and amiodarone on plasma thyroid hormones and the possible consequences on the response of the heart to ischemia. Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day per os) were administered for 2 weeks in normal and thyroxine-treated animals (25 microg/100 g body weight od sc, for 2 weeks), while animals without amiodarone and dronedarone served as controls. Isolated rat hearts were perfused in a Langendorff mode and subjected to 20 and 30 min of zero-flow global ischemia followed by 45 min of reperfusion. Functional changes were assessed by measuring left ventricular developed pressure (LVDP) under resting conditions and in response to ischemia-reperfusion, LVDP%, as well as the severity of ischemic contracture. Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals. In thyroxine-treated animals, amiodarone increased T4/T3 ratio but T4, T3 and rT3 levels were not altered. Basal functional parameters and ischemic contracture did not change by amiodarone and/or dronedarone neither in normal nor in thyroxine-treated hearts. In normal hearts, postischemic functional recovery, LVDP%, was not altered by amiodarone or dronedarone administration. LVDP% was statistically higher in thyroxine-treated hearts than in normal and this beneficial effect was not abolished by amiodarone or dronedarone treatment.
Pantos
Constantinos
C
Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., 11527 Goudi, Greece. cpantos@cc.uoa.gr
Mourouzis
Iordanis
I
Delbruyère
Martine
M
Malliopoulou
Vassiliki
V
Tzeis
Stylianos
S
Cokkinos
Demosthenis D
DD
Nikitas
Nikos
N
Carageorgiou
Hariclia
H
Varonos
Dennis
D
Cokkinos
Dennis
D
Nisato
Dino
D
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000077764:Dronedarone; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood*
D013963:Thyroid Hormones; D000077764:Dronedarone; D000638:Amiodarone