Beneficial effects of intravenous iron therapy in a rat model of heart failure with preserved systemic iron status but depleted intracellular cardiac stores

Aleksandra Paterek,Barbara Sochanowicz,Marta Kępska,Michał Mączewski,Ewelina Chajduk,Urszula Mackiewicz,Halina Polkowska-Motrenko,Marcin Kruszewski,Przemysław Leszek,Joanna Kołodziejczyk

doi:10.1038/s41598-018-33277-2

Abstract

Iron deficiency (ID) commonly occurs in chronic heart failure (HF) and is associated with poor prognosis. Neither its causes nor pathophysiological significance are clearly understood. We aimed to assess iron status and the effect of iron supplementation in the rat model of post-myocardial infarction (MI) HF. Four weeks after induction of MI to induce HF or sham surgery, rats received intravenous iron (ferric carboxymaltose) or saline, 4 doses in 1-week intervals. HF alone did not cause anemia, systemic or myocardial ID, but reduced myocardial ferritin, suggesting depleted cardiomyocyte iron stores. Iron therapy increased serum Fe, ferritin and transferrin saturation as well as cardiac and hepatic iron content in HF rats, but did not increase myocardial ferritin. This was accompanied by: (1) better preservation of left ventricular (LV) ejection fraction and smaller LV dilation, (2) preservation of function of Ca2+ handling proteins in LV cardiomyocytes and (3) reduced level of inflammatory marker, CRP. Furthermore, iron supplementation did not potentiate oxidative stress or have toxic effects on cardiomyocyte function, but increased activity of antioxidant defenses (cardiac superoxide dismutase). Despite lack of systemic or myocardial ID we found evidence of depleted cardiomyocyte iron stores in the rat model of HF. Furthermore we observed positive effect of iron supplementation and confirmed safety of iron supplementation in this setting.

Highlights

Iron is a vital element for the body, especially for metabolically active tissues such as myocardium
Congestion, impaired nutrition, reduced intracellular uptake of iron due to reduced cellular transferrin receptor 1 (TfR1), iron sequestration associated with chronic inflammation accompanying heart failure (HF), and intracellular abnormalities of iron handing in cardiomyocytes) or to the factors related to co-morbidities and concomitant medications[2]
The mean infarct size evaluated by transthoracic echocardiography (Fig. 1B–D) in both HF groups did not differ at randomization and at the end of the study (4 and 8 weeks after myocardial infarction (MI) induction, respectively) (Table 1)

Summary

Introduction

Iron is a vital element for the body, especially for metabolically active tissues such as myocardium. We have previously shown that myocardial iron content in HF patients is lower than expected based on systemic iron turnover parameters (ferritin concentration, transferrin saturation)[3]. To make this even more complex, there can be iron shifts between specific intracellular compartments despite normal myocardial iron content[4]. In HF patients ID is associated with poor prognosis, independently of hemoglobin concentration[1,5,6] It is associated with disease symptoms, limited exercise tolerance, poor quality of life and increased risk of hospitalization[1,5]. Safety of treatment with intravenous iron in HF is of utmost importance

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