title: Delayed postconditioning in the mouse heart in vivo.
abstract: BACKGROUND
  Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size. Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients.
  
  
  RESULTS
  Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR(60')). Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (Δt) after reopening of the coronary artery (Δt=10 seconds, 1, 5, 10, 15, 20, 30, and 45 minutes; PostC(Δt)). Infarct size/area at risk was reduced by 71% in PostC(Δ1) compared with IR(60') mice (P=5×10(-6)). There was a linear correlation (r(2)=0.91) between infarct size and Δt, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when Δt time increased. The protective effect of PostC(Δ1) and PostC(Δ15) was still effective when the duration of reperfusion was prolonged to 24 hours (IR(24 hours); PostC(Δ1) and PostC(Δ15) versus IR(24 hours), P=0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release.
  
  
  CONCLUSIONS
  This study in our in vivo mouse model of myocardial IR shows for the first time that delaying the intervention of postconditioning to 30 minutes does not abrogate the cardioprotective effect of postconditioning. This finding provides evidence that the time window of protection afforded by postconditioning may be larger than initially reported.
authors.affiliation: CNRS, UMR, Institut de Génomique Fonctionnelle, INSERM, France.
authors.forename: François
authors.initials: F
authors.lastname: Roubille
authors.forename: Alicia
authors.initials: A
authors.lastname: Franck-Miclo
authors.forename: Aurélie
authors.initials: A
authors.lastname: Covinhes
authors.forename: Chrystel
authors.initials: C
authors.lastname: Lafont
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cransac
authors.forename: Stéphane
authors.initials: S
authors.lastname: Combes
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontanaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Sportouch-Dukhan
authors.forename: Christelle
authors.initials: C
authors.lastname: Redt-Clouet
authors.forename: Joël
authors.initials: J
authors.lastname: Nargeot
authors.forename: Christophe
authors.initials: C
authors.lastname: Piot
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Barrère-Lemaire
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D057775:Ischemic Postconditioning / Q000379:methods*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D013997:Time Factors