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Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury.

Hansson, Magnus LU ; Llwyd, Osian; Morin, Didier; de Paulis, Damien; Arnoux, Thomas; Gouarné, Caroline; Koul, Sasha LU ; Engblom, Henrik LU ; Bordet, Thierry and Tissier, Renaud, et al. (2015) In European Journal of Pharmacology 760(Apr 17). p.7-19
Abstract
The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size... (More)
The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size following ischemia/reperfusion. In biopsies from the left ventricle of pigs subjected to in vivo occlusion/reperfusion, TRO40303 specifically preserved respiratory functions in the peri-infarct zone whereas mild hypothermia preserved both the ischemic core area and the peri-infarct zones. Additionally in this pig model, only hypothermia reduced infarct size. We conclude that mild hypothermia provided protection in all models by reducing the detrimental effects of ischemia, and when initiated before occlusion, reduced subsequent reperfusion damage leading to a smaller infarct. By contrast, although TRO40303 provided similar protection to MitoQ in vitro and offered specific protection against some aspects of reperfusion injury in vivo, this was insufficient to reduce infarct size. (Less)
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European Journal of Pharmacology
volume
760
issue
Apr 17
pages
7 - 19
publisher
Elsevier
external identifiers
  • pmid:25895640
  • wos:000355664200002
  • scopus:84928887184
ISSN
1879-0712
DOI
10.1016/j.ejphar.2015.04.009
language
English
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yes
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d5ca756e-96b9-4f9c-a943-79d0f4f77eb2 (old id 5341192)
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http://www.ncbi.nlm.nih.gov/pubmed/25895640?dopt=Abstract
date added to LUP
2015-05-04 17:28:34
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2017-07-30 03:09:23
@article{d5ca756e-96b9-4f9c-a943-79d0f4f77eb2,
  abstract     = {The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size following ischemia/reperfusion. In biopsies from the left ventricle of pigs subjected to in vivo occlusion/reperfusion, TRO40303 specifically preserved respiratory functions in the peri-infarct zone whereas mild hypothermia preserved both the ischemic core area and the peri-infarct zones. Additionally in this pig model, only hypothermia reduced infarct size. We conclude that mild hypothermia provided protection in all models by reducing the detrimental effects of ischemia, and when initiated before occlusion, reduced subsequent reperfusion damage leading to a smaller infarct. By contrast, although TRO40303 provided similar protection to MitoQ in vitro and offered specific protection against some aspects of reperfusion injury in vivo, this was insufficient to reduce infarct size.},
  author       = {Hansson, Magnus and Llwyd, Osian and Morin, Didier and de Paulis, Damien and Arnoux, Thomas and Gouarné, Caroline and Koul, Sasha and Engblom, Henrik and Bordet, Thierry and Tissier, Renaud and Arheden, Haakan and Erlinge, David and Halestrap, Andrew P and Berdeaux, Alain and Pruss, Rebecca M and Schaller, Sophie},
  issn         = {1879-0712},
  language     = {eng},
  number       = {Apr 17},
  pages        = {7--19},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2015.04.009},
  volume       = {760},
  year         = {2015},
}