title: Argon Exposure Induces Postconditioning in Myocardial Ischemia-Reperfusion.
abstract: OBJECTIVE
  Cardioprotection against ischemia-reperfusion (I/R) damages remains a major concern during prehospital management of acute myocardial infarction. Noble gases have shown beneficial effects in preconditioning studies. Because emergency proceedings in the context of myocardial infarction require postconditioning strategies, we evaluated the effects of argon in such protocols on mammalian cardiac tissue.
  
  
  METHODS
  In rat, cardiac I/R was induced in vivo by transient coronary artery ligature and cardiac functions were evaluated by magnetic resonance imaging. Hypoxia-reoxygenation (H/R)-induced arrhythmias were evaluated in vitro using intracellular microelectrodes on both rat-isolated ventricle and a model of border zone in guinea pig ventricle. Hypoxia-reoxygenation loss of contractile force was assessed in human atrial appendages. In those models, postconditioning was induced by 5 minutes application of argon at the time of reperfusion.
  
  
  RESULTS
  In the in vivo model, I/R produced left ventricular ejection fraction decrease (24%) and wall motion score increase (36%) which was prevented when argon was applied in postconditioning. In vitro, argon postconditioning abolished H/R-induced arrhythmias such as early after depolarizations, conduction blocks, and reentries. Recovery of contractile force in human atrial appendages after H/R was enhanced in the argon group, increasing from 51% ± 2% in the nonconditioned group to 83% ± 7% in the argon-treated group ( P < .001). This effect of argon was abolished in the presence of wortmannin and PD98059 which inhibit prosurvival phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and MEK/extracellular receptor kinase 1/2 (ERK 1/2), respectively, or in the presence of the mitochondrial permeability transition pore opener atractyloside, suggesting the involvement of the reperfusion injury salvage kinase pathway.
  
  
  CONCLUSIONS
  Argon has strong cardioprotective properties when applied in conditions of postconditioning and thus appears as a potential therapeutic tool in I/R situations.
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Katrien
authors.initials: K
authors.lastname: Blanchart
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Souplis
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Lemaitre
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Legallois
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Coulbault
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Simard
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Abraini
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Hanouz
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: René
authors.initials: R
authors.lastname: Rouet
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sallé
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Guinamard
authors.affiliation: 1 Signalisation, Electrophysiologie et Imagerie des lésions d'ischémie-reperfusion myocardique, Normandie Univ, UNICAEN, Caen, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Manrique
mesh_terms: D000818:Animals; D001128:Argon / Q000008:administration & dosage*; D020517:Atrial Appendage / Q000187:drug effects / Q000503:physiopathology; D006168:Guinea Pigs; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001128:Argon
keywords: argon; cardioprotection; ischemia–reperfusion; noble gas; postconditioning