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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 orcid ; 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
760
issue
Apr 17
pages
7 - 19
publisher
Elsevier
external identifiers
  • pmid:25895640
  • wos:000355664200002
  • scopus:84928887184
  • pmid:25895640
ISSN
1879-0712
DOI
10.1016/j.ejphar.2015.04.009
language
English
LU publication?
yes
id
d5ca756e-96b9-4f9c-a943-79d0f4f77eb2 (old id 5341192)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25895640?dopt=Abstract
date added to LUP
2016-04-01 10:14:27
date last changed
2024-01-21 08:57:35
@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}},
  doi          = {{10.1016/j.ejphar.2015.04.009}},
  volume       = {{760}},
  year         = {{2015}},
}