LAUSR

Current treatments for myocardial infarction (MI) aim to remove the vascular occlusion and reperfuse the infarcted tissue. While reperfusion can salvage myocardium, it can also increase damage to the unsalvageable tissue, one mechanism of which is hemorrhage; the resulting blood and iron deposits increase edema and inflammation. We hypothesize that removing these iron deposits with the iron chelating drug deferiprone (DFP) will reduce inflammation and lead to faster healing post-MI. Using a swine model of ischemia-reperfusion, pigs were administered either DFP or saline for four weeks post-MI. Cardiac MRI tracked heart function, infarct progression (via late gadolinium enhancement), hemorrhage (via T2* imaging), and edema (via T2 imaging) at baseline and 1 day, 1 week, and 4 weeks post-MI. Animals were then sacrificed and hearts were processed for histology. Treatment with DFP decreased the presence of iron in the infarct compared to saline by one week post-MI, as shown by increased T2* values. DFP treatment also decreased end diastolic wall swelling, suggesting less inflammation post-MI. To support this, T2 values and histology both revealed trends toward less edema with DFP. Histology also showed trended increases in fibroblast proliferation and collagen deposition at four weeks post-MI in the treatment group, consistent with a faster resolution to scar. Ventricular remodeling (by ventricular volumes), infarct size (by MRI, histology and blood Troponin I levels), and infarct transmurality were all unaffected, but contractile function improved with DFP treatment: ejection fraction and wall thickening both improved faster. In conclusion, DFP treatment successfully reduced hemorrhagic iron within the infarct as compared to saline, indicating a clearing of the iron byproducts. Treatment also decreased wall swelling, suggesting reduced inflammation, and improved contractile function. In the infarct, reduced swelling could indicate faster remodeling and a faster resolution to scar, and histology confirms a more progressed scar structure with DFP treatment. Overall, iron chelation appears to be a promising therapy that could reduce the negative effects of hemorrhage and speed the functional recovery of patients post-MI.