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Mild hypothermia reduces per-ischemic reactive oxygen species production and preserves mitochondrial respiratory complexes.
MedLine Citation:
PMID:  22796545     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Mitochondrial dysfunction is critical following ischemic disorders. Our goal was to determine whether mild hypothermia could limit this dysfunction through per-ischemic inhibition of reactive oxygen species (ROS) generation. METHODS: First, ROS production was evaluated during simulated ischemia in an vitro model of isolated rat cardiomyocytes at hypothermic (32°C) vs normothermic (38°C) temperatures. Second, we deciphered the direct effect of hypothermia on mitochondrial respiration and ROS production in oxygenated mitochondria isolated from rabbit hearts. Third, we investigated these parameters in cardiac mitochondria extracted after 30-min of coronary artery occlusion (CAO) under normothermic conditions (CAO-N) or with hypothermia induced by liquid ventilation (CAO-H; target temperature: 32°C). RESULTS: In isolated rat cardiomyocytes, per-ischemic ROS generation was dramatically decreased at 32 vs 38°C (e.g., -55±8% after 140min of hypoxia). In oxygenated mitochondria isolated from intact rabbit hearts, hypothermia also improved respiratory control ratio (+22±3%) and reduced H(2)0(2) production (-41±1%). Decreased oxidative stress was further observed in rabbit hearts submitted to hypothermic vs normothermic ischemia (CAO-H vs CAO-N), using thiobarbituric acide-reactive substances as a marker. This was accompanied by a preservation of the respiratory control ratio as well as the activity of complexes I, II and III in cardiac mitochondria. CONCLUSION: The cardioprotective effect of mild hypothermia involves a direct effect on per-ischemic ROS generation and results in preservation of mitochondrial function. This might explain why the benefit afforded by hypothermia during regional myocardial ischemia depends on how fast it is instituted during the ischemic process.
Authors:
Renaud Tissier; Mourad Chenoune; Sandrine Pons; Roland Zini; Lys Darbera; Fanny Lidouren; Bijan Ghaleh; Alain Berdeaux; Didier Morin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-11
Journal Detail:
Title:  Resuscitation     Volume:  -     ISSN:  1873-1570     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Affiliation:
Inserm, U955, Equipe 3, Créteil, 94000, France; Université Paris Est, Faculté de Médecine, Créteil, 94000, France; Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, 94704, France.
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