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

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.

Ivabradine is as effective as metoprolol in the prevention of ventricular arrhythmias in acute non-reperfused myocardial infarction in the rat

“…Regional LV wall motion abnormalities were quantitated using the wall motion index (WMI). We have previously shown that WMI is a good echocardiographic indicator of infarct size in the rat 34 . Rats with WMI < 18 were considered to have moderate or large MI (WMI = 18 corresponds to an infarct involving ~ 28% of the LV myocardium).…”

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

“…While it is true that all cell types are affected by iron unbalance, two organs are paradigmatic in the ferroptosis scenario; the heart is one of the principal utilisers of iron while the liver is principally responsible for iron handling. Iron level alterations are detrimental in both directions as proved by the poor prognosis of heart failure patients with commonly associated iron deficiency [ 132 ]. Accordingly, iron mishandling has been proposed to be a major trigger for severe injury to cardiomyocytes and hepatocytes and therefore an important player in developing heart and liver failure [ 55 , 133 ].…”

Treatment of hypoxia‐dependent cardiovascular diseases by myo‐inositol trispyrophosphate (ITPP)‐enhancement of oxygen delivery by red blood cells

“…But neither erythropoietin analogs that increased haemoglobin concentration 6 nor intravenous iron that provided an essential element not only for haemoglobin, but also other enzymes involved in cardiac energetics 7 provided unequivocal benefits in human clinical trials, though recent data, including our own work, 8 suggest that iron may be of some value here. But neither erythropoietin analogs that increased haemoglobin concentration 6 nor intravenous iron that provided an essential element not only for haemoglobin, but also other enzymes involved in cardiac energetics 7 provided unequivocal benefits in human clinical trials, though recent data, including our own work, 8 suggest that iron may be of some value here.…”

“…They were mainly focused on increasing the concentration of haemoglobin, an oxygen-carrying protein. But neither erythropoietin analogs that increased haemoglobin concentration 6 nor intravenous iron that provided an essential element not only for haemoglobin, but also other enzymes involved in cardiac energetics 7 provided unequivocal benefits in human clinical trials, though recent data, including our own work, 8 suggest that iron may be of some value here.…”