BJA/RCoA Project Grant
The successful applicants for the BJA / RCoA Project Grant were:
Principal Applicant
Dr Robert Dickinson
Department of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London
Title
The role of the NMDA-receptor glycine site in xenon neuroprotection against traumatic brain injury.
Amount
£50,000
Abstract
Traumatic brain injury (TBI) is a major cause of morbidity and mortality throughout the world, but there are no clinically effective interventions. We showed xenon is neuroprotective in a model of TBI and prevents the spread of secondary injury. However, the molecular target(s) underlying xenon neuroprotection in TBI are unknown, as are the mechanism(s) by which secondary injury spreads. Xenon inhibits NMDA-receptors and we made an advance in understanding xenon's molecular action at NMDA-receptors, by showing it competes with the co-agonist glycine. This project will determine whether NMDA-receptor glycine-site inhibition underlies xenon neuroprotection in TBI, whether xenon protects equally in different brain-regions and investigate how secondary injury spreads. Discovering the molecular mechanisms of xenon neuroprotection against TBI will provide a foundation for future translational studies that could eventually lead to the use of xenon in brain-injured patients in neuro intensive care units.
Final Report from Dr R Dickinson (227 KB)
Principal Applicant
Dr Jaideep Pandit
Consultant Anaesthetist, Honorary Senior Lecturer & Fellow of St John's College, Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford
Title
Are volatile anaesthetic combinations antagonistic or addictive in their effect on human hypoxic ventilatory response and on task-like K + channel activity in glomus cells?
Amount
£46,005
Abstract
Molecular/cellular mechanisms are lacking for the known depressive effect of volatile anaesthetics on human ventilatory responses to hypoxia (VHR). Different anaesthetics depress VHR to different degrees and N2O magnifies VHR. We ask: "Do combinations of agents with different activities show antagonism (as most other drugs competing for the same receptor) or additivity/synergism, as is consistent with the 'anaesthetic paradigm'?" Carotid body O2 sensing involves membrane depolarisation through inhibition of background K+ channels. We recently identified a TASK-like K+ channel sensitive to both hypoxia and halothane and further, found isoflurane and sevoflurane to have less effect than halothane on this channel's activity, consistent with their rank order of potency on human VHR. The current paradigm is that anaesthetics are additive. Because of the very direct link between channel activity, glomus cell and then whole body hypoxic response, the respiratory system uniquely lends itself to test the alternative possibility that agents instead act antagonistically.
Final Report from Prof J Pandit (158 KB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr Kyle Pattinson
MRC Clinician Scientist Fellow, Nuffield Department of Anaesthetics and Oxford Centre for Functional Magnetic Resonance of the Brain University of Oxford, John Radcliffe Hospital, Oxford
Title
MRI biomarkers of vasospasm in subarachnoid haemorrhage - proof of concept study
Amount
£7,800
Abstract
Vasospasm (or "delayed ischaemic neurological deficit") is a major cause of morbidity and mortality following subarachnoid haemorrhage. Successful targeted treatment requires an accurate, non-invasive, and reproducible measure of cerebral perfusion. Current techniques are limited in their clinical application as they only image larger arteries and require the use of contrast agents and/or ionising radiation. We propose to trial novel magnetic resonance imaging techniques that do not require exogenous contrast agents and will demonstrate quantitative measures of cerebral perfusion at the tissue level. Animal subarachnoid haemorrhage models have demonstrated alterations in natural fluctuations in vascular responsiveness during vasospasm. We will determine whether this can be demonstrated in humans and if this may provide an early marker of impending vasospasm. The imaging measures that we propose could be used to monitor a patient's vasospasm and response to treatment. This would potentially facilitate the early and targeted use of vasospasm therapies and so reduce long-term morbidity and mortality.
Final Report from Dr K Pattinson (237 KB)
Principal Applicant
Dr Suellen Walker
Clinical Senior Lecturer and Honorary Consultant in Paediatric Anaesthesia and Pain Medicine, UCL Institute of Child Health & Department of Anaesthesia, Great Ormond Street Hospital, London
Title
Opioid analgesia for neonatal surgery: long term impact on responses to future injury and analgesic efficacy
Amount
£48,065
Abstract
There is increasing clinical and laboratory evidence that injury in early life can produce long-term changes in sensory function and influence future pain responses. In addition, both the pharmacokinetic and pharmacodynamic profile of analgesics change during postnatal development, and limit the ability to extrapolate data from older children to neonates and infants. The experiments in this proposal investigate the interactions between surgical injury and opioid administration in the postnatal period on changes in sensory processing and sensitivity to opioids in later life. The results will provide preclinical data to assist in the choice of analgesic regimen for perioperative analgesia in neonates and infants.
Second Year Progress Report from Dr S Walker (15 KB)
Final Project Report from Dr S Walker (25 KB)
Article entitled, 'Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity' published in Brain, November 18 2011
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Professor Nigel Webster
Professor of Anaesthesia & Intensive Care & Honorary Consultant, Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry, University of Aberdeen
Title
Cardiac Biomarkers in ICT Patients: What Do They Mean?
Amount
£17,112
Abstract
Small increases in cardiac troponin levels are seen commonly in ICU patients but the meaning of these increases are not clear. Several cardiac biomarkers have been shown to be useful in other clinical situations but it is not known how these relate to echocardiographic changes in ICU patients. In particular the role of the velocity and/or magnitude of changes in these biomarkers in the ICU population is not known. We propose to measure sequential levels of cardiac troponin I, Nterminal pro-B-type natriuretic peptide and H-type fatty acid binding protein and to relate these to echocardiographic changes in ICU patients. Results from each biomarker will be analysed for clinical sensitivity, specificity, and positive/negative predictive value, alone and in combination. Clinical data including diagnosis, APACHE II score, use of inotropes and vasoconstrictors, development of organ dysfunction assessed by SOFA score, and survival will be recorded. It hoped that this pilot study will inform a subsequent substantial grant application for the study of the utility of certain key cardiac biomarkers in an ICU population.
July 2011 Progress Report from Prof N Webster (21 KB)
December 2012 Progress Report from Prof N Webster (34 KB)
