BJA/RCoA Project Grant
The successful applicant for the BJA / RCoA Project Grant was:
Principal Applicant
Professor A Absalom
Professor of Anaesthesiology, University Medical Centre Groningen, Netherlands
Title
Pilot study of the extent and distribution of microglial activation in young and elderly rats undergoing cardiopulmonary bypass, as detected by Positron Emission Tomography, using the tracer [-PK11195, and immunochemistry staining techniques.
Amount
£19,200
Abstract
For some time it has been suspected that postoperative cognitive dysfunction (POCD) after cardiac surgery is caused by inflammation resulting from cardiopulmonary bypass (CPB), amplified by the surgery and anaesthesia. Recently, the significance of neuroinflammation has been questioned. In the future, we are planning a series of studies to investigate the extent, distribution, severity and long-term consequences of neuroinflammation following cardiac surgery with or without CPB. One of the key tools we plan to use is positron emission tomography (PET) with the tracer [-PK11195, which can provide in vivo identification of neuroinflammation since it attaches to activated microglia. So far this PET tracer has not been used to study neuronal inflammation in surgical patients. Thus, the aim of this application is to seek funding for a proof of concept study, to determine whether or not a rat model of cardiopulmonary bypass produces neuronal inflammation, as detected by standard histology and immunochemistry techniques, and whether the [-PK11195 tracer is able to detect this inflammation. An additional aim is to gather pilot data that we hope will inform future studies of the influence of priming, by ageing and neuro-degenerative disorders, on the neuronal inflammatory response to cardiac surgery.
First Year Progress Report from Prof A Absalom (26 KB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr M Wilson
Lecturer in Physiology, Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London
Title
The influence of obesity on the pathobiology of acute lung injury
Amount
£44,927
Abstract
Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are major causes of morbidity and mortality within the intensive care unit. The current proposal is designed to address the impact of obesity on the pathobiology of ALI. Contrary to expectation there is evidence from clinical studies that obesity may be protective for ALI patients, although this has not been investigated experimentally. We will explore the mechanisms underlying such protection using clinically relevant, in vivo mouse models of ALI induced by mechanical ventilation, acid aspiration and lipopolysaccharide. Experiments will be carried out in lean and obese mice, with obesity induced by feeding a high fat diet. Specifically, we will investigate the consequences of obesity on the pulmonary inflammatory response, and the ability of the lungs to resolve injury. If (as preliminary studies indicate) obesity is indeed protective during ALI, understanding the mechanisms behind this may help us identify novel targets for the treatment of ALI/ARDS, e.g. adipokine-based therapies.
Progress Report from Dr M Wilson (73 KB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr R Pearse
Clinical Senior Lecturer & Consultant in Intensive Care Medicine, National Institute for Health Research Clinician Scientist, Barts and The London School of Medicine and Dentistry, London
Title
Investigation of the effects of dopexamine on leucocyte-endothelial interaction, microvascular flow and tissue inflammatory pathways and the underlying mechanisms in a rodent model of laparotomy and endotoxaemia.
Amount
£49,438
Abstract
Tissue injury of major surgery causes a range of microvascular effects which are linked to organ failure and death. Adrenergic agents appear to have important effects on the microcirculation following tissue injury. However, whilst over half of all intensive care patients receive adrenergic agents, the effects of these drugs are poorly understood. Adrenergic agents may have important effects on inflammation and immune function which could be beneficial or harmful. A better understanding of these effects will allow us to refine their use in clinical practice and develop future novel agents. We therefore propose to investigate in detail the microvascular effects of dopexamine. Using an established laboratory model of laparotomy and sepsis we will measure the effects of dopexamine on leucocyte-endothelial interactions using intravital microscopy. Cardiac output monitoring and laser Doppler flowmetry will be used to quantify effects on global and tissue-microvascular perfusion. Ex vivo wire myography will be used to investigate the response of mesenteric arterial strips to dopexamine and the receptors responsible. Our preliminary data suggest that dopexamine may be an antagonist at á-adrenoceptors. We will then undertake in vitro studies to investigate the effects of dopexamine on intracellular inflammatory signalling pathways through actions at specific adrenoceptors.
First Year Progress Report from Dr R Pearse (63 KB)
Final Report from Dr R Pearse (85 KB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr P Shortland
Centre for Neuroscience & Trauma, Blizard Institute for Cell & Molecular Sciences, Barts & The London, Queen Mary's School of Medicine & Dentistry, London
Title
Novel strategies to ameliorate pain association with avulsion injury.
Amount
£46,476
Abstract
Motor vehicle accidents are the most common cause of injuries involving the avulsion of spinal roots from the cord. This causes physical tearing of one or more dorsal and/or ventral roots from the spinal cord. The site of injury is usually the brachial or lumbo-sacral plexus and results in chronic, intractable neuropathic pain. The mechanisms underlying the pain are poorly understood and difficult to treat with current drug therapies. Our previous work on neuropathic pain induced by avulsion implicates increased neuronal loss and ischeamia as potential causes. However, it is unclear whether ischaemia directly contributes to the cell death. Our aims are: 1) to see if avulsion injury permanently alters the oxygen supply to the spinal cord in both the injured segments and the adjacent uninjured segments using photoplethysmography; 2) to see if this change can be prevented or reversed using currently available drugs that are known to be neuroprotective and have angiogenic properties. The drugs under investigation will be erythropoietin (EPO) and a structurally related analog, carbamylated-EPO. Changes in evoked pain behaviour and neuronal survival will be correlated with oxygen levels detected by photoplethysmography. The results of this study may provide new ways to treat pain associated with avulsion injury.
Final Report from Dr Shortland (17 KB)
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Dr G Minto
Consultant, Directorate of Anaesthesia Theatres & Pain, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth
Title
Does intra-operative goal directed fluid therapy reduce clinically important post-operative complications in patients undergoing elective non-vascular major abdominal surgery associated with extensive tissue trauma?
Amount
£25,000
Abstract
Goal Directed Fluid therapy (GDT) refers to fluid management targeted toward improving the cardiac output to set levels. It is hypothesised that the benefits of intraoperative GDT accrue from the maintenance of sufficient end organ perfusion to meet tissue metabolic requirements throughout major surgery. The microcirculation is the "coalface" of end organ perfusion. Side stream dark field (SDF) imaging (essentially high resolution video clips) allows real-time quantification of sublingual capillary vessel abundance and flow. Previous trials suggest that intra-operative GDT guided by oesophageal Doppler Monitoring reduces median hospital length of stay after major colorectal surgery, however our own recent work suggests that this may be true only for rectal resections. We propose an RCT to test our hypothesis that intraoperative GDT may decrease important complications (recorded with a validated Postoperative Morbidity Survey) in patients having operations associated with considerable tissue trauma such as rectal resection or pancreatoduodenectomy. Concurrently we will use SDF to track changes in the microcirculation. Pre-operative Cardiopulmonary Exercise (CPX) testing can identify patients with poor aerobic fitness and potentially inadequate oxygen delivery. Do patients who are categorised 'high risk' on the basis of this test result benefit more from GDT than a fitter cohort?
Final Report from Dr G Minto.pdf (82 KB)
