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Human physiology: the pulmonary circulation, age, iron, and exercise

Dr Tom Smith measuring a volunteer's pulmonary artery pressure during an experiment in Peru
Dr Tom Smith measuring a volunteer's pulmonary artery pressure during an experiment in Peru

We tend to take for granted our capacity to cycle at speed to work and to walk up stairs until something subtly impairs the hugely complex metabolic machine that carries us around: such as breathing the rarefied air in the high mountains or experiencing the bronchospasm of a bout of asthma. Our research is directed towards using the latest techniques and new modelling approaches to help us understand the behaviour of the respiratory and cardiovascular systems, particularly in stressful situations. My current work focuses on the way the blood vessels in the lungs of humans can affect these systems.

The blood vessels of the lungs are able to change their diameter to have the beneficial effect of regulating the efficiency with which the flow of blood to different parts of the lungs gets matched to the flow of gas into the nearby small airways of the lungs. If too many of the blood vessels band together to constrict, they can have the adverse effect of making it difficult for the right side of the heart to deliver blood through the lungs to the left side of the heart, thereby reducing the flow of blood round the body overall. This problem can become particularly taxing during exercise.

These lung blood vessels have long been known to be markedly influenced by brief periods of low levels of oxygen (hypoxia). Our recent studies have been showing some novel striking effects of prolonged hypoxia, of high and low levels of carbon dioxide, and of drugs―including the steroid dexamethasone used to prevent and treat mountain sickness. A lively focus in our research at the moment is our recent discovery of the role of iron in regulating the lung blood vessels, part of a widespread role of iron in the body via its influence on the hypoxia inducible factor gene transcription regulator.

We have shown, in a number of settings, including at high altitude in Peru, that raising the level of iron in the body dilates the blood vessels in the lungs, and reduces the pressure against which the heart works to deliver blood to the body. A recent project with a colleague in Birmingham has shown that elderly people have a particular feature of high blood pressure in their pulmonary arteries, and we know that this gets worse on exercise. So a current project is examining the hypothesis that making healthy people between the ages of 50-80 years replete in iron will reduce the constriction of lung blood vessels and enhance their capacity to undertake vigorous cycle exercise.

I work closely with Peter Robbins and a team of graduate students and post-doctoral researchers in the Department. Other projects include examining the physiological changes brought about in healthy but iron-deficient young people given intravenous iron, exploring the therapeutic role of iron in patients with chronic obstructive pulmonary disease, and looking for reasons for the variability between people in the way they respond to hypoxia. I am also examining a number of issues relating physiology to anaesthesia, which is the clinical specialty in which I continue to look after patients, and from which junior doctors commonly like to come to undertake research in the lab.


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