title: Chronic manifestation of postreperfusion intramyocardial hemorrhage as regional iron deposition: a cardiovascular magnetic resonance study with ex vivo validation.
abstract: BACKGROUND
  Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored.
  
  
  RESULTS
  Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment-elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo-) and remote territories (P<0.001); however, T2* values of nonhemorrhagic (Hemo-) and remote territories were not different (P=0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and 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 with the other (control) groups (P<0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of 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]); R(2)=0.7 and P<0.001. The monoclonal antibody Mac387 stains, along with Perls 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 the chronic phase of myocardial infarction.
authors: Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Avinash
authors: A
authors: Kali
authors: Andreas
authors: A
authors: Kumar
authors: Ivan
authors: I
authors: Cokic
authors: Richard L Q
authors: RL
authors: Tang
authors: Sotirios A
authors: SA
authors: Tsaftaris
authors: Matthias G
authors: MG
authors: Friedrich
authors: Rohan
authors: R
authors: Dharmakumar
mesh_terms: D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016014:Linear Models; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors
chemical_list: D007501:Iron