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Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor

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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 60nM 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.

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Authors and Affiliations

  1. Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., 11527, Goudi, Athens, Greece

    Constantinos Pantos, Iordanis Mourouzis, Vassiliki Brozou & Georgios Galanopoulos

  2. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Dennis V. Cokkinos

  3. Department of Anaesthesia and Cardiovascular Critical Care, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece

    Theodosios Saranteas & Georgia Kostopanagiotou

Authors
  1. Constantinos Pantos
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  2. Iordanis Mourouzis
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  3. Theodosios Saranteas
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  4. Vassiliki Brozou
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  5. Georgios Galanopoulos
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  6. Georgia Kostopanagiotou
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  7. Dennis V. Cokkinos
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Correspondence to Constantinos Pantos.

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Pantos, C., Mourouzis, I., Saranteas, T. et al. Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor. Mol Cell Biochem 353, 235–241 (2011). https://doi.org/10.1007/s11010-011-0791-8

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  • DOI: https://doi.org/10.1007/s11010-011-0791-8

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