Experimental Iron Deficiency in Rats: Mechanical and Electrophysiological Alterations in the Cardiac Muscle

Abstract

1. Our aim was to investigate the effect of experimental iron deficiency on cardiac functional properties. We recorded ventricular isometric twitch, action potentials and the L-type Ca2+ current in isolate ventricular myocytes from iron-deficient rats and control rats. 2. Twitch tension and maximal rates of tension activation and relaxation were reduced in iron-deficient compared with control rats, whereas twitch duration was prolonged. Isoproterenol (10-(6) mol/l) augmented tension in iron-deficient rats (P < 0.05), but only moderately affected control rats. In contrast, maximal rates of tension activation and relaxation were increased equally by isoproterenol in the two groups. 3. To determine the mechanism(s) responsible for the reduced mechanical function in iron-deficient rats, action potentials and the L-type Ca2+ current (with or without isoproterenol) were recorded in both groups. 4. The L-type Ca2+ current was smaller in ventricular myocytes from control rats than in those from iron-deficient rats; at a membrane potential of 0 mV, L-type Ca2+ current amplitudes were -1.44 +/- 0.18 and -0.97 +/- 0.07 nA in myocytes from control and iron-deficient rats respectively (P < 0.05). 5. Action potential duration was markedly shortened in myocytes from iron-deficient compared with control rats; action potential duration at 50% repolarization was 12.0 +/- 1.6 and 7.2 +/- 1.4 ms in myocytes from control and iron-deficient rats respectively (P < 0.01). These iron deficiency-induced electrophysiological alterations most probably contribute to the depressed mechanical function in iron-deficient rats. 6. The L-type Ca2+ current was augmented equally by isoproterenol in the two groups, suggesting that the enhanced inotropic responsiveness in iron-deficient rats was not due to an increased response of the L-type Ca2+ current. 7. These results may have an important implication for anaemic (iron-deficient) patients; the attenuation of their cardiac mechanical performance may be compensated by an increased reactivity to beta-adrenergic stimulation.

Left ventricular ejection fraction recovery in patients with heart failure treated with intravenous iron: a pilot study

“…Experimental studies have shown that ID induced cardiac dysfunction13 and cardiac hypertrophy, characterized by aberrant mitochondrial and irregular sarcomere organization 14…”

“…12 Despite the crucial role of iron in the physiology of cardiovascular system, this element remains understudied outside of the erythropoietic system. Experimental studies have shown that ID induced cardiac dysfunction 13 and cardiac hypertrophy, characterized by aberrant mitochondrial and irregular sarcomere organization. 14 Given previous evidence, it seems plausible to speculate that ID may play a causative role in the pathophysiology of HF beyond anaemia.…”

Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration

“…A previous investigation [20] has suggested that altered myocardial function develops in iron-deficient rats with changes in ventricular contractility, maximal rates of contraction and relaxation, action potentials and L-type Ca 2+ currents. In addition, the twitch duration was prolonged similar to that observed in diabetes and heart failure [20]. These electrophysiological changes may contribute to depressed cardiac function with iron deficiency.…”

Cardiorenal Syndrome and the Role of the Bone-Mineral Axis and Anemia

“…In vitro studies suggest that iron deficiency directly impairs myocyte mechanical function 71 and that iron deficiency anemia induces LVH 72 characterized by myocyte hypertrophy and hypercellularity. 73 Anemia also may exacerbate heart failure through a series of downstream events in which tissue hypoxia and nitric oxide release cause peripheral vasodilation and blood pressure decreases.…”