Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction
| Autor: | Michael Spino, John C. Wood, Bradley H. Strauss, Vrajlal S. Rabadia, Bita Behrouzi, Jennifer Barry, Jill J. Weyers, John T. Connelly, Dino Manca, Nilesh R. Ghugre, Xiuling Qi, Graham A. Wright |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cardiotonic Agents Physiology Swine medicine.medical_treatment Myocardial Infarction Inflammation Hemorrhage 030204 cardiovascular system & hematology Iron Chelating Agents Targeted therapy Iron chelation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Internal medicine Edema medicine Animals Deferiprone cardiovascular diseases Myocardial infarction Cardioprotection Iron Chelator Ventricular Remodeling business.industry Myocardium medicine.disease Disease Models Animal 030104 developmental biology chemistry Cardiology Female medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | Basic research in cardiology. 115(3) |
| ISSN: | 1435-1803 |
| Popis: | Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia–reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI. |
| Databáze: | OpenAIRE |
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