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.