Iron Status and Hypoxic Pulmonary Vascular Responses

University of Oxford31 enrolled

Overview

On exposure to hypoxia (low oxygen) the normal response is for pulmonary arterial systolic blood pressure (PASP, blood pressure through the lungs) to increase. We have previously shown that raising iron by giving an infusion of iron into a vein reduces this pressure rise and that lowering iron by giving a drug that binds iron, magnifies this response. This is potentially a clinically important observation since iron-deficient people may be at increased risk of pulmonary hypertension if exposed transiently or permanently to hypoxia due to lung disease or residence at high altitude; furthermore if this were true then intravenous iron could be an important treatment in this patient group in the event of hypoxic exposure. The observed effects of iron on PASP are likely to be because iron levels affect oxygen sensing. Low iron levels make the body behave as if exposed to low oxygen by inhibiting the breakdown of the family of oxygen-sensing transcription factors, 'hypoxia inducible factor' or HIF. This includes one of the body's normal responses to low oxygen levels - raising blood pressure through the lungs. This study will answer the question (1) do iron-deficient volunteers have a greater rise in PASP with hypoxia than those who are iron-replete, and (2) does giving intravenous iron cause a greater reduction in the rise in PASP in those who are iron-deficient than iron-replete? The purpose of this study is not to test the safety or clinical efficacy of iron which is already known.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Lung Hypoxia

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Willing and able to give informed consent for participation in the study * Men and women aged 18 years or older and generally in good health * Detectable tricuspid regurgitation on echocardiography during both normoxia and hypoxia enabling measurement of pulmonary arterial pressure * For iron-deficient volunteers: ferritin ≤15microg/L and transferrin saturation \<16% * For iron-replete volunteers: ferritin ≥20microg/L and transferrin saturation ≥20% Exclusion Criteria: * Haemoglobin \<8.0g/dl * Haemoglobinopathy * Iron overload defined as ferritin \>300microg/L * Hypoxia at rest or on walking (SaO2 \<94%) or significant comorbidity that may affect haematinics, pulmonary vascular or ventilatory responses, e.g. current infection, a chronic inflammatory condition, known cardiovalvular lesion or pulmonary hypertension, uncontrolled asthma or chronic obstructive pulmonary disease * Exposure to high altitude (\>2,500m) within the previous six weeks or air travel \>4 hours within the previous week * Iron supplementation or blood transfusion within the previous 6 weeks * Pregnancy or breast feeding

Outcomes

Primary Outcomes

∆PASP in iron-replete compared to iron-deficient volunteers

Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers

Time frame: During six hours of hypoxia without prior iron infusion

Secondary Outcomes

∆PASP, with versus without prior iron infusion, in iron-replete compared to iron-deficient volunteers

Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers, with versus without a prior iron infusion

Time frame: During two six-hour periods of hypoxia; assessments separated by at least a week

Blood parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers

Time frame: After six hours of hypoxia, at both study assessments

Ventilation parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers

Time frame: During six hours of hypoxia, at both study assessments