Author + information
- Received October 19, 2014
- Revision received November 5, 2014
- Accepted November 6, 2014
- Published online February 3, 2015.
- Rodrigo Fernández-Jiménez, MD∗,†,
- Javier Sánchez-González, PhD∗,‡,
- Jaume Agüero, MD∗,
- Jaime García-Prieto, BSc∗,
- Gonzalo J. López-Martín, Tech∗,
- José M. García-Ruiz, MD∗,
- Antonio Molina-Iracheta, DVM∗,
- Xavier Rosselló, MD∗,
- Leticia Fernández-Friera, MD, PhD∗,§,
- Gonzalo Pizarro, MD∗,‖,
- Ana García-Álvarez, MD, PhD∗,
- Erica Dall'Armellina, MD, DPhil¶,
- Carlos Macaya, MD, PhD†,
- Robin P. Choudhury, DM¶,
- Valentin Fuster, MD, PhD∗,# and
- Borja Ibáñez, MD, PhD∗,†∗ ()
- ∗Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
- †Hospital Universitario Clínico San Carlos, Madrid, Spain
- ‡Philips Healthcare, Madrid, Spain
- §Hospital Universitario Montepríncipe, Madrid, Spain
- ‖Hospital Universitario Quirón Universidad Europea de Madrid, Madrid, Spain
- ¶Oxford Acute Vascular Imaging Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
- #The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Borja Ibáñez, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
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.
Objectives 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.
This work was supported by a competitive grant from the Ministry of Economy and Competitiveness (MINECO), Fondo Europeo de Desarrolo Regional (FEDER) Carlos III Institute of Health–Fondo de Investigación Sanitaria (PI13/01979), and in part by FP7-PEOPLE-2013-ITN Next Generation Training in Cardiovascular Research and Innovation–Cardionext. This study forms part of a Master Research Agreement between CNIC and Philips Healthcare. QMass software use was partially supported by a scientific collaboration with Medis Medical Imaging Systems BV. The Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation support the CNIC. Dr. Fernández-Jiménez is a recipient of a Rio Hortega fellowship from the Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III; and has received an FICNIC fellowship from the Fundació Jesús Serra, the Fundación Interhospitalaria de Investigación Cardiovascular, and the CNIC. Dr. Sánchez-González is an employee of Philips Healthcare. Dr. Aguero is an FP7-PEOPLE-2013-ITN-Cardionext fellow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Derek Yellon, PhD, DSc, served as Guest Editor for this paper.
- Received October 19, 2014.
- Revision received November 5, 2014.
- Accepted November 6, 2014.
- 2015 American College of Cardiology Foundation