Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia

Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 hours. Thus, any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6-h) hypoxia on four separate days (days 0, 1, 8 and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ~50%, and this response remained suppressed on both days 8 and 43 (p<0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation and hepcidin concentration rose significantly (p<0.001, p <0.005 and p<0.001, respectively) and values for transferrin concentration fell significantly (p<0.001). These changes remained significant at day 43. We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension

Perspective Chapter: Evolution of Techniques to Assess Vascular Impedance in Patients with Aortic Stenosis

Aortic stenosis (AS) once was conceptualized as a mechanical problem with a fixed left ventricular (LV) afterload because of an obstructive valve. With time, there has been growing recognition that AS functions more like a series circuit, with important contributions from the ventricle through to the vasculature. Emerging evidence suggests that higher blood pressure and increased arterial stiffness, synonymous with vascular aging, increases global LV afterload in patients with AS. This in turn, has adverse consequences on quality-of-life measures and survival. Although traditional methods have emphasized measurement of the transvalvular pressure gradient, focusing on valvular hemodynamics alone may be inadequate. By definition, total vascular load of the human circulation includes both steady and pulsatile components. Steady load is best represented by the systemic vascular resistance whereas pulsatile load occurs because of wave reflections and vascular stiffness, and is often referred to as the valvulo-arterial impedance. In the following Review, we evaluate existing and upcoming methods to assess vascular load in patients with AS in order to better understand the effects of vascular aging on this insidious disease process