Abstract

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.

Restoration of coronary blood flow after a heart attack may lead to reperfusion injury and pathologic iron deposition. Here, the authors perform magnetic susceptibility imaging showing its association with iron in a large animal model of myocardial infarction during wound healing, and showing feasibility in acute myocardial infarction patients undergoing percutaneous coronary intervention.

Details

Title
Iron imaging in myocardial infarction reperfusion injury
Author
Moon, Brianna F 1   VIAFID ORCID Logo  ; Iyer, Srikant Kamesh 2   VIAFID ORCID Logo  ; Hwuang Eileen 1   VIAFID ORCID Logo  ; Solomon, Michael P 1 ; Hall, Anya T 1 ; Kumar Rishabh 3 ; Josselyn, Nicholas J 2 ; Higbee-Dempsey, Elizabeth M 4 ; Tsourkas, Andrew 1   VIAFID ORCID Logo  ; Imai Akito 5 ; Okamoto Keitaro 5 ; Saito Yoshiaki 5 ; Pilla, James J 2 ; Gorman, Joseph H, III 5 ; Gorman, Robert C 5 ; Tschabrunn Cory 6 ; Keeney, Samuel J 7 ; Castillero Estibaliz 8   VIAFID ORCID Logo  ; Ferrari, Giovanni 8 ; Jockusch Steffen 9 ; Wehrli, Felix W 2 ; Shou Haochang 10 ; Ferrari, Victor A 6 ; Han Yuchi 6 ; Gulhane Avanti 2 ; Litt, Harold 2 ; Matthai, William 11 ; Witschey Walter R 12   VIAFID ORCID Logo 

 University of Pennsylvania, Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Department of Biophysics, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Department of Surgery, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Department of Medicine, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
 University of Pennsylvania, Department of Surgery, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770) 
 Columbia University Irving Medical Center, Department of Surgery, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
 Columbia University, Department of Chemistry, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
10  University of Pennsylvania, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
11  University of Pennsylvania, Department of Medicine, Penn Presbyterian Medical Center, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
12  University of Pennsylvania, Department of Bioengineering, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); University of Pennsylvania, Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2418452467
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.