Abstract
In older individuals, pulmonary artery pressure rises markedly during exercise, probably due in part to increased pulmonary vascular resistance and in part to an increase in left‐heart filling pressure. Older individuals also show more marked pulmonary vascular response to hypoxia at rest. Treatment with intravenous iron reduces the rise in pulmonary artery pressure observed during hypoxia. Here, we test the hypothesis that intravenous iron administration may also attenuate the rise in pulmonary artery pressure with exercise in older individuals. In a randomized double‐blind placebo‐controlled physiology study in 32 healthy participants aged 50–80 years, we explored the hypothesis that iron administration would deliver a fall in systolic pulmonary artery pressure (SPAP) during moderate cycling exercise (20 min duration; increase in heart rate of 30 min−1) and a change in maximal cycling exercise capacity (V˙O2max). Participants were studied before, and at 3 h to 8 weeks after, infusion. SPAP was measured using Doppler echocardiography. Iron administration resulted in marked changes in indices of iron homeostasis over 8 weeks, but no significant change in hemoglobin concentration or inflammatory markers. Resting SPAP was also unchanged, but SPAP during exercise was lower by ~3 mmHg in those receiving iron (P < 0.0001). This effect persisted for 8 weeks. Although V˙O2max remained unaffected in the iron‐replete healthy participants studied here, this study demonstrates for the first time the ability of intravenous iron supplementation to reduce systolic pulmonary artery pressure during exercise.
Highlights
Increasing age is associated with a reduction in exercise capacity
In a randomized double-blind placebo-controlled physiology study in 32 healthy participants aged 50–80 years, we explored the hypothesis that iron administration would deliver a fall in systolic pulmonary artery pressure (SPAP) during moderate cycling exercise (20 min duration; increase in heart rate of 30 minÀ1) and a change in maximal cycling exercise capacity (V_O2max)
This effect persisted for 8 weeks. We interpret these findings in the context of (1) considering whether the fall in the PO2 of venous blood during exercise might act as a stimulus to “hypoxic pulmonary vasoconstriction” even though airbreathing exercise is usually not regarded as a form of hypoxia; (2) studies finding that administration of vasodilators can reduce pulmonary artery pressure during exercise in hypoxia; (3) observations showing a reduction in hypoxic pulmonary vasoconstriction in humans at rest, induced by administration of iron; and (4) the finding that iron administration can enhance exercise capacity in heart failure
Summary
Increasing age is associated with a reduction in exercise capacity. we do not find this surprising, the factors accounting for it are unclear. One potential contributory factor that has emerged in recent studies is the marked rise in pulmonary artery pressure that occurs during exercise in older people, which increases the workload of the right ventricle for any given cardiac output. Similar findings were reported by Mahjoub and colleagues using echocardiographic measurement of systolic pulmonary artery pressure (SPAP) over the age range 20–80 years and including both light and heavy exercise (Mahjoub et al 2009). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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