title: Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor.
abstract: We have previously shown that acute thyroid hormone treatment could limit reperfusion injury and increase post-ischemic recovery of function. In the present study, we further explore potential initiating mechanisms of this response. Thus, isolated rat hearts were subjected to 30 min zero-flow global ischemia (I) followed by 60-min reperfusion (R). Reperfusion injury was assessed by post-ischemic recovery of left ventricular developed pressure (LVDP%) and LDH release. T3 at a dose of 60 nM which had no effect on contractile function of non-ischemic myocardium, significantly increased LVDP% [48% (2.9) vs. 30.2% (3.3) for untreated group, P < 0.05] and reduced LDH release [8.3 (0.3) vs. 10 (0.42) for untreated group, P < 0.05] when administered at R. T4 (60 and 400 nM) had no effect on contractile function either in non-ischemic or ischemic myocardium. Administration of debutyl-dronedarone (DBD), a TRα1 antagonist abolished the T3-limiting effect on reperfusion injury: Thus, co-administration of T3 and DBD resulted in significantly lower LVDP%, [23% (4.7) vs. 48% (2.9) for T3 group, P < 0.05] and higher LDH release [9.9 (0.3) vs. 8.3 (0.3), for T3 group, P < 0.05]. In conclusion, acute T3 and not T4 treatment will be able to protect against reperfusion injury. T3 can exert this beneficial effect on ischemic myocardium at a dose that has no effects on non-ischemic myocardium. Acute T3-limiting effect on reperfusion injury is mediated, at least in part, via TRα1 receptor.
authors: Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., 11527 Goudi, Athens, Greece. cpantos@med.uoa.gr
authors: Constantinos
authors: C
authors: Pantos
authors: Iordanis
authors: I
authors: Mourouzis
authors: Theodosios
authors: T
authors: Saranteas
authors: Vassiliki
authors: V
authors: Brozou
authors: Georgios
authors: G
authors: Galanopoulos
authors: Georgia
authors: G
authors: Kostopanagiotou
authors: Dennis V
authors: DV
authors: Cokkinos
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000077764:Dronedarone / Q000031:analogs & derivatives; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D037021:Thyroid Hormone Receptors alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D037021:Thyroid Hormone Receptors alpha; C585281:debutyl-dronedarone; D014284:Triiodothyronine; D000077764:Dronedarone; D000638:Amiodarone; D013974:Thyroxine