Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.

Myocardial ischemic postconditioning (PosC) describes an acquired resistance to lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria per...

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Main Authors: Jianhui Li, Noureddine Loukili, Nathalie Rosenblatt-Velin, Pal Pacher, François Feihl, Bernard Waeber, Lucas Liaudet
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3707883?pdf=render
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author Jianhui Li
Noureddine Loukili
Nathalie Rosenblatt-Velin
Pal Pacher
François Feihl
Bernard Waeber
Lucas Liaudet
author_facet Jianhui Li
Noureddine Loukili
Nathalie Rosenblatt-Velin
Pal Pacher
François Feihl
Bernard Waeber
Lucas Liaudet
author_sort Jianhui Li
collection DOAJ
description Myocardial ischemic postconditioning (PosC) describes an acquired resistance to lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria permeability transition. Recent observations indicated that PostC is associated with free radicals generation, including nitric oxide (NO(.)) and superoxide (O2 (.-)), and that cardioprotection is abrogated by antioxidants. Since NO. And O2 (. -) react to form peroxynitrite, we hypothesized that postC might trigger the formation of peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds ischemia/30 seconds reperfusion) was applied at the end of index ischemia. In a subgroup of rats, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (FeTPPS) was given intravenously (10 mg/kg(-1)) 5 minutes before PostC. Myocardial nitrotyrosine was determined as an index of peroxynitrite formation. Infarct size (colorimetric technique and plasma creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip pressure transducer), were determined. A significant generation of 3-nitrotyrosine was detected just after the PostC manoeuvre. PostC resulted in a marked reduction of infarct size, CK release and LV systolic dysfunction. Treatment with FeTPPS before PostC abrogated the beneficial effects of PostC on myocardial infarct size and LV function. Thus, peroxynitrite formed in the myocardium during PostC induces cardioprotective mechanisms improving both structural and functional integrity of the left ventricle exposed to ischemia and reperfusion in vivo.
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spelling doaj.art-ec0a7f27ed7740539c185773e4599ff12022-12-22T01:51:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7033110.1371/journal.pone.0070331Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.Jianhui LiNoureddine LoukiliNathalie Rosenblatt-VelinPal PacherFrançois FeihlBernard WaeberLucas LiaudetMyocardial ischemic postconditioning (PosC) describes an acquired resistance to lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria permeability transition. Recent observations indicated that PostC is associated with free radicals generation, including nitric oxide (NO(.)) and superoxide (O2 (.-)), and that cardioprotection is abrogated by antioxidants. Since NO. And O2 (. -) react to form peroxynitrite, we hypothesized that postC might trigger the formation of peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds ischemia/30 seconds reperfusion) was applied at the end of index ischemia. In a subgroup of rats, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (FeTPPS) was given intravenously (10 mg/kg(-1)) 5 minutes before PostC. Myocardial nitrotyrosine was determined as an index of peroxynitrite formation. Infarct size (colorimetric technique and plasma creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip pressure transducer), were determined. A significant generation of 3-nitrotyrosine was detected just after the PostC manoeuvre. PostC resulted in a marked reduction of infarct size, CK release and LV systolic dysfunction. Treatment with FeTPPS before PostC abrogated the beneficial effects of PostC on myocardial infarct size and LV function. Thus, peroxynitrite formed in the myocardium during PostC induces cardioprotective mechanisms improving both structural and functional integrity of the left ventricle exposed to ischemia and reperfusion in vivo.http://europepmc.org/articles/PMC3707883?pdf=render
spellingShingle Jianhui Li
Noureddine Loukili
Nathalie Rosenblatt-Velin
Pal Pacher
François Feihl
Bernard Waeber
Lucas Liaudet
Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
PLoS ONE
title Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
title_full Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
title_fullStr Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
title_full_unstemmed Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
title_short Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.
title_sort peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo
url http://europepmc.org/articles/PMC3707883?pdf=render
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