MYOCARDIAL LABILE IRON DYNAMICS IN ACUTE AND CHRONIC IRON OVERLOAD

The labile iron pool (LIP) typically constitutes a small proportion of total cellular iron, but is responsible for cytotoxicity when in excess. The heart is particularly prone to taking up excess iron from the circulation, however changes in cardiac cellular LIP in response to acute or chronic iron loading are unexplored. We used iron-caged luciferin (ICL-1), a novel luminescent reporter of the LIP in luciferase transgenic mice to determine how cardiac LIP changes in two conditions – firstly, treatment with patient-equivalent dose of ferric carboxymaltose (FCM, Ferinject®), a third-generation intravenous iron therapy, and secondly, an inducible haemochromatosis model giving progressive iron overload. Haemochromatosis was not associated with significant changes in cardiac LIP despite hepatic iron loading. In contrast, IV iron treatment significantly increased cardiac LIP just 1 hour after administration, in the absence of hepatic iron elevation but associated with significant increases in serum iron levels. Additionally, we found evidence to suggest preferential right atrial uptake after IV iron treatment. Chamber-specific differences in expression of genes regulating iron homeostasis were identified which could account for this. Indeed, right atrial tissue displayed significantly greater expression of hepcidin and significantly lower expression of ferritin when compared to tissue from other chambers. These results indicate that FCM acutely elevates cardiac LIP. Further studies are warranted to examine the functional effects of FCM on the heart, and to explore intracardiac differences in iron homeostasis, all of which will are relevant to understanding the response to and safety of FCM in patients.