title: Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern: imaging and histological tissue characterization.
abstract: BACKGROUND
  It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon.
  
  
  OBJECTIVE
  This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion.
  
  
  METHODS
  The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls.
  
  
  RESULTS
  In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h.
  
  
  CONCLUSIONS
  Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernández-Jiménez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Philips Healthcare, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-González
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Agüero
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: García-Prieto
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Gonzalo J
authors.initials: GJ
authors.lastname: López-Martín
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: García-Ruiz
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molina-Iracheta
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Rosselló
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Montepríncipe, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernández-Friera
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Quirón Universidad Europea de Madrid, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Pizarro
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Álvarez
authors.affiliation: Oxford Acute Vascular Imaging Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Erica
authors.initials: E
authors.lastname: Dall'Armellina
authors.affiliation: Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.affiliation: Oxford Acute Vascular Imaging Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Choudhury
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Clínico San Carlos, Madrid, Spain. Electronic address: bibanez@cnic.es.
authors.forename: Borja
authors.initials: B
authors.lastname: Ibáñez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D013552:Swine; D014867:Water / Q000032:analysis
chemical_list: D014867:Water
keywords: CMR; MRI; T2; myocardial infarction; pig; water content