Metabolomic Analysis of Biofluids in Limb Ischaemia and Reperfusion
Research type
Research Study
Full title
Metabolomic Analysis of Biofluids in Limb Ischaemia and Reperfusion
IRAS ID
293948
Contact name
Madelaine Gimzewska
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
2 years, 3 months, 4 days
Research summary
Research Summary
Limb ischaemia is a condition where the blood supply to a leg or arm (limb) is reduced, causing the tissue to become starved of oxygen (ischaemic). Tissues need oxygen to function healthily, and tissues which are starved of oxygen become injured. At present doctors rely on examining the limb to assess the extent of tissue injury; there are no blood tests or scans which reliably indicate tissue damage severity.
When a limb becomes ischaemic, the cells in the limb adapt their metabolism to manage under oxygen deprived conditions. These changes in metabolism release chemicals which can be detected in the cells and surrounding tissues. When blood flow is restored (termed reperfusion), further cellular metabolic changes occur, releasing chemicals into the tissues. Some basic chemical changes which occur in ischaemic and reperfused tissue are already understood, but these are not yet specific enough to help make management decisions in limb ischaemia. This work aims to use a scientific method based on computational analysis of spectral information generated from analysis of tissue samples to identify and understand the chemical differences between normal, reversibly ischaemic, irreversibly ischaemic and reperfusing limb tissues. The analysis of metabolic changes in limb ischaemia and reperfusion has potential for direct translational impact; enabling the identification of clinical biomarkers, more sensitive detection of ischaemia, improved stratification of tissue viability, indicating potential targets for tailored resuscitative and management strategies, and increased knowledge of potential pharmacotherapy that can target biological pathways involved in ischaemic tissue injury.Summary of Results
This project set out to see if a special fluid called interstitial fluid (the liquid that surrounds muscle cells) could be collected from the leg and studied to give doctors new information about how well the muscle is coping when blood supply is reduced. Using a very fine tube (microdialysis), we showed that this can be done safely and comfortably.
We compared this muscle fluid with blood samples in healthy volunteers while a tourniquet was used to briefly stop, then restore, blood flow to the leg. The muscle fluid proved to be much more sensitive to these changes than blood. Almost half of the chemical signals we measured changed during reduced blood supply and recovery, compared with fewer than one in six in blood.
We have now also collected samples from patients with both sudden and long-term reduced blood flow to the legs, and are currently analysing these in detail.REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
21/EM/0189
Date of REC Opinion
1 Oct 2021
REC opinion
Further Information Favourable Opinion