Oxford Respiratory Group
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Prof Pandit awarded Spring Silver Medal, College of Anaesthetists of Ireland 2012
19 papers published 2011-12
The Oxford Respiratory Group works collaboratively on a range of projects dedicated to Respiratory Control. Professor Pandit's group studies anaesthetic effects on oxygen sensing and also focusses on clinical research related to effects of anaesthetics on respiration and anaesthetic techniques on the lungs and airway.
General anaesthetics have profound effects upon the control of breathing, one of which is to suppress a protective ventilatory response to low blood oxygen. This hypoxic ventilatory response (HVR) is mediated principally by the carotid body, a peripheral chemoreceptor. These organs contain specialized sensory cells, type-1 or glomus cells, which detect oxygen levels and signal to the respiratory control centers in the brainstem via afferent nerves. The process by which type-1 cells signal hypoxia involves the modulation of a specific group of potassium channels called TASK channels. These channels are members of the tandem-p-domain K-channel family and, like some other members of the channel family, have a marked sensitivity to certain types of inhalational general anaesthetic.
The objective of this project is to investigate both the molecular nature of these channels and their sensitivity to a range of anaesthetic agents so that we may better understand the role of these channels in determining the depressive effects of anaesthetics on HVR.
We have made the important discovery that anaesthetic agents compete infra-additively at a single receptor (TASK channel), challenging the paradigm that these drugs act via non-receptor (additive-only) mechanisms.
Our research involves the use of a number of techniques from whole animal physiology (non-invasive measurements of breathing in transgenic animals) through single cell calcium imaging, electrophysiology (patch clamp) and some molecular biology. The project may also include parallel studies in humans.
This research will not only help unravel key molecular mechanisms underlying the actions of this poorly understood, yet widely used, group of drugs, but may also be useful in the future design of anaesthetics which retain the ability to induce unconsciousness, whilst avoiding the adverse (possibly dangerous) side-effect of depressing ventilatory responses to hypoxia.
The link of this work to fundamental mechanisms has led to our also working in the field of 'awareness during anaesthesia' and Professor Pandit has led the Royal College of Anaesthetists’ international project (NAP5) on this important complication. This has led to important practice recommendations and ongoing research.
The link of this work to clinical anaesthesia and airway management has led to a number of publications in the important field of 'difficult airway management' in collaboration with the national Difficult Airway Society.