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Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion?

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Abstract

Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfusion injury in a Langendorff–perfused rat heart model of 30 min zero-flow ischaemia and 60 min of (R) with or without T3 (40 µg/l) at R, T3-R60, n = 11 and CNT-R60, n = 10, respectively. Furthermore, phosphorylated levels of intracellular kinases were measured at 5, 15 and 60 min of R. T3 markedly improved postischaemic recovery of left ventricular developed pressure (LVDP%); 56.0% (SEM, 4.4) in T3-R60 versus 38.8% (3.1) in CNT-R60, P < 0.05. Furthermore, LDH release was significantly lower in T3-R60. Apoptosis detection by fluorescent probe optical imaging showed increased fluorescent signal in CNT-R60 hearts, while the signal was hardly detectable in T3-R60 hearts. Similarly, caspase-3 activity was found to be 78.2 (8.2) in CNT-R60 vs 40.5 (7.1) in T3-R60 hearts, P < 0.05. This response was associated with significantly lower levels of phospho-p38 MAPK at any time point of R. No significant changes in phospho- ERK1/2 and JNK levels were observed between groups. Phospho–Akt levels were significantly lower in T3 treated group at 5 min and no change in phospho–Akt levels were observed at 15 and 60 min between groups. In conclusion, T3 administration at reperfusion can improve postischaemic recovery of function while limiting apoptosis. This may constitute a paradigm of a positive inotropic agent with anti-apoptotic action suitable for supporting hemodynamics in the clinical setting of ischaemia-reperfusion.

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Acknowledgments

This work was supported by the “Alexander S. Onassis” foundation and the Haute-Normandie region.

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Authors and Affiliations

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

    Constantinos Pantos, Iordanis Mourouzis, Theodosios Saranteas, Philipos Perimenis, Danai Spanou & Georgia Kostopanagiotou

  2. Quidd Saint Etienne du Rouvray, Rouen, France

    Guillaume Clavé, Heidi Ligeret, Pauline Noack-Fraissignes & Marc Massonneau

  3. CNRS UMR 6014, IRCOF, Université de Rouen, Mont-Saint-Aignan, France

    Pierre-Yves Renard

  4. 1st Cardiology Dept., Onassis Cardiac Surgery Center, Kallithea, Athens, Greece

    Dennis V. Cokkinos

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

    Dennis V. Cokkinos

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  1. Constantinos Pantos
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  2. Iordanis Mourouzis
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Correspondence to Constantinos Pantos.

Additional information

Returned for 1. Revision: 11 August 2008 1. Revision received: 26 September 2008

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Pantos, C., Mourouzis, I., Saranteas, T. et al. Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion?. Basic Res Cardiol 104, 69–77 (2009). https://doi.org/10.1007/s00395-008-0758-4

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