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Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury.
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- Hansson, Magnus (author)
- Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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Llwyd, Osian (author)
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Morin, Didier (author)
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de Paulis, Damien (author)
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Arnoux, Thomas (author)
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Gouarné, Caroline (author)
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- Koul, Sasha (author)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Engblom, Henrik (author)
- Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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Bordet, Thierry (author)
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Tissier, Renaud (author)
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Arheden, Haakan (author)
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- Erlinge, David (author)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Halestrap, Andrew P (author)
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Berdeaux, Alain (author)
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Pruss, Rebecca M (author)
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Schaller, Sophie (author)
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 760:Apr 17, s. 7-19
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Hansson, Magnus
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Llwyd, Osian
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Morin, Didier
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de Paulis, Damie ...
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Arnoux, Thomas
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Gouarné, Carolin ...
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show more...
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Koul, Sasha
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Engblom, Henrik
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Bordet, Thierry
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Tissier, Renaud
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Arheden, Haakan
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Erlinge, David
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Halestrap, Andre ...
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Berdeaux, Alain
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Pruss, Rebecca M
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Schaller, Sophie
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
- Articles in the publication
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European Journal ...
- By the university
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Lund University