Keith Dorrington

The Department has provided a splendid environment in which to study the cardiovascular and respiratory systems, and in particular how the behaviour of the blood vessels in the lungs impacts on these systems.

I graduated in Engineering Science in the University of Oxford in 1974. An interest in materials science led me to research the thermodynamic properties and molecular structure of the connective tissue protein elastin for a DPhil with Gerry McCrum in 1977. We demonstrated that this major component of skin, arteries, and ligaments displayed ‘entropy elasticity’, analogous to natural rubber, a type of behaviour that contrasts with the ‘internal energy elasticity' of most structural materials.

In 1982 I qualified in Medicine and developed Anaesthesia as my specialist clinical interest. There was a lively interest in Oxford in developing artificial lungs for cardiopulmonary bypass in surgery; I worked with Keith Sykes and Brian Bellhouse on the design and application of an artificial lung for the long-term support of patients in Intensive Care who have severe respiratory failure. Our efforts contributed to the current evidence-based use of this ‘extracorporeal respiratory support’ in certain patient groups, such as in premature newborn babies and patients with Covid-19 pneumonia. In this technique, an artificial lung beside the patient’s bed supports respiratory gas exchange much as a dialysis machine is used to support renal function. Theoretical analysis of gas exchange in these artificial lungs and in a wide range of equipment used by anaesthetists was the basis for my text "Anaesthetic & Extracorporeal Gas Transfer" (OUP, 1989) and the degree of DM.

I have enjoyed working closely with Peter Robbins since coming to the Department in 1989. Study topics have included the effects of different therapeutic and anaesthetic agents on the regulation of breathing; the role of active transport of salt and water across the lung alveolar epithelium in preventing the lungs from filling with liquid; the modelling of systemic arterial blood pressure regulation; and the responses of the blood vessels of the lungs to low oxygen (hypoxia) and high carbon dioxide.

The capacity of the blood vessels in the lungs to constrict in response to a few minutes of hypoxia had been known for many years, but we were able to show that an ‘acclimatization’ of the blood vessels to hypoxia occurs, in the sense that the constrictor response continues to intensify over hours, even if the stimulus remains constant. This hypoxic pulmonary vasoconstriction helps to regulate the efficiency of gas exchange in the lungs, and affects the risk of developing pulmonary oedema at high altitude. Our studies have investigated the effects of drugs, iron homeostasis, and ascent to altitude in Peru on this important reflex. A recent project examined how a single intravenous dose of iron delivers a prolonged reduction in the constriction of blood vessels in the lungs of people aged 50-80 years during exercise, and suggests a possible mechanism whereby iron benefits patients with heart failure even if they are not anaemic. Several of our studies have probed the role of Hypoxia-Inducible Factor (HIF) in human physiology and been co-investigations with Prof Sir Peter Ratcliffe, who was awarded the Nobel Prize for Physiology & Medicine in 2019 for his work elucidating the HIF pathway.

My other recent projects have included the study of cognitive decline in middle-aged people following surgery and anaesthesia, a critique of the practice of pre-operative starvation, an extensive review of the mechanisms of action of antihypertensive drugs, and an exploration of the long history of computational modelling of blood pressure regulation. Being recently retired from full-time duties, I am no longer in a position to recruit my own research students, but I continue to support research in the laboratory of Prof Robbins. I teach in the first and second years of our undergraduate Medicine course: lectures, practical classes, and tutorials. Academic life is never boring.