eprintid: 1509
rev_number: 7
eprint_status: archive
userid: 35
dir: disk0/00/00/15/09
datestamp: 2013-03-05 15:03:04
lastmod: 2013-03-12 09:32:21
status_changed: 2013-03-05 15:03:04
type: article
metadata_visibility: show
creators_name: Kali, Avinash
creators_name: Kumar, Andreas
creators_name: Cokic, Ivan
creators_name: Tang, Richard
creators_name: Tsaftaris, Sotirios A.
creators_name: Friedrich, Matthias G
creators_name: Dharmakumar, Rohan
creators_id: 
creators_id: 
creators_id: 
creators_id: 
creators_id: sotirios.tsaftaris@imtlucca.it
creators_id: 
creators_id: 
title: Chronic Manifestation of Post-Reperfusion Intramyocardial Hemorrhage as Regional Iron Deposition: A Cardiovascular MR Study with Ex-vivo Validation
ispublished: pub
subjects: QA75
subjects: RC
divisions: CSA
full_text_status: none
keywords: acute myocardial infarction; cardiac magnetic resonance imaging; hemorrhage; inflammation
note: Published online before print February 12, 2013
abstract: Background—Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the make-up and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored.

Methods and Results—Patients (n = 15; 3 women), recruited after successful PCI for first ST-elevation myocardial infarction, underwent Cardiovascular Magnetic Resonance (CMR) imaging on day 3 and month 6 post-PCI. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* CMR on day 3 (n = 11), showed persistent T2* losses co-localized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than non-hemorrhagic (Hemo-) and remote territories (p<0.001); however, T2* values of non-hemorrhagic (Hemo-) and remote territories were not different (p=0.51. Canines (n = 20), subjected to ischemia-reperfusion (I/R) injury (n = 14), underwent CMR on days 3 and 56 post I/R injury. Similarly, sham-operated animals (Shams; n = 3) were imaged using CMR at similar time points. Subsequently, hearts were explanted, imaged ex-vivo, and samples of Hemo+, Hemo-, remote and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared to the other (control) groups (p<0.001), and Perl's stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than the control groups (p<0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and -log([Fe]) (R2=0.7; p<0.001). The monoclonal antibody Mac387 stains, along with Perl's stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition.

Conclusions—Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in chronic phase of myocardial infarction. 
date: 2013-02
date_type: published
publication: Circulation: Cardiovascular Imaging
publisher: American Heart Association
id_number: 10.1161/CIRCIMAGING.112.000133
refereed: TRUE
issn: 1941-9651
official_url: http://dx.doi.org/10.1161/CIRCIMAGING.112.000133
citation:   Kali, Avinash and Kumar, Andreas and Cokic, Ivan and Tang, Richard and Tsaftaris, Sotirios A. and Friedrich, Matthias G and Dharmakumar, Rohan  Chronic Manifestation of Post-Reperfusion Intramyocardial Hemorrhage as Regional Iron Deposition: A Cardiovascular MR Study with Ex-vivo Validation.  Circulation: Cardiovascular Imaging.   ISSN 1941-9651      (2013)