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Impaired lymphatic clearance and pro-inflammatory cytokines in mechanically loaded tissue - implications in pressure ulcer aetiology

Impaired lymphatic clearance and pro-inflammatory cytokines in mechanically loaded tissue - implications in pressure ulcer aetiology
Impaired lymphatic clearance and pro-inflammatory cytokines in mechanically loaded tissue - implications in pressure ulcer aetiology
Despite lymphatic function regularly being proposed as one of the causative mechanisms in the development of pressure ulcers, there has been a paucity of research regarding the effect of compression on lymphatic function in human tissues. This has motivated the present work, which has developed and validated techniques to safely assess lymphatic function and concomitantly measure the physiochemical response in the skin, directly under and following the application of a uniaxial load in human volunteers.Lymphatic function was assessed through optical imaging of an intradermally injected near-infrared fluorophore, namely indocyanine green (ICG), which is rapidly cleared in lymph. Pro-inflammatory biomarkers were recovered by two minimally invasive collection techniques involving microdialysis and Sebutape™. Through the application of established image processing concepts to NIR lymphangiography for the first time, a method for objectively quantifying parameters of active lymphatic clearance is also described.The results of the study suggest that applied pressure of 60 mmHg for a period of 40 minutes can lead to changes in both novel pro-inflammatory and lymphatic parameters, not previously described in the literature. During the loading period, induced expression or accumulation of IL-6 and IL-8 in the interstitium was observed (p < 0.01). For IL-6, this upregulation was sustained for over 40 minutes post loading (p < 0.01). The same loading protocol was associated, through categorical analysis, with impaired lymph formation in lymphatic capillaries and disrupted valve function in collecting vessels directly under the load. The velocity of active lymphatic drainage along the loaded pathway was also significantly reduced (p < 0.05).The findings from this thesis support the proposal that impaired lymphatic function, with a corresponding accumulation of harmful biomolecules, are feasible mechanisms which can contribute to the development of pressure ulcers. The present study strongly supports further exploration of these hypotheses using the techniques described.
University of Southampton
Gray, Robert James
10320802-d462-4bfc-92f4-43561788bfd4
Gray, Robert James
10320802-d462-4bfc-92f4-43561788bfd4
Bader, Daniel
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Voegeli, David
e6f5d112-55b0-40c1-a6ad-8929a2d84a10

Gray, Robert James (2017) Impaired lymphatic clearance and pro-inflammatory cytokines in mechanically loaded tissue - implications in pressure ulcer aetiology. University of Southampton, Doctoral Thesis, 250pp.

Record type: Thesis (Doctoral)

Abstract

Despite lymphatic function regularly being proposed as one of the causative mechanisms in the development of pressure ulcers, there has been a paucity of research regarding the effect of compression on lymphatic function in human tissues. This has motivated the present work, which has developed and validated techniques to safely assess lymphatic function and concomitantly measure the physiochemical response in the skin, directly under and following the application of a uniaxial load in human volunteers.Lymphatic function was assessed through optical imaging of an intradermally injected near-infrared fluorophore, namely indocyanine green (ICG), which is rapidly cleared in lymph. Pro-inflammatory biomarkers were recovered by two minimally invasive collection techniques involving microdialysis and Sebutape™. Through the application of established image processing concepts to NIR lymphangiography for the first time, a method for objectively quantifying parameters of active lymphatic clearance is also described.The results of the study suggest that applied pressure of 60 mmHg for a period of 40 minutes can lead to changes in both novel pro-inflammatory and lymphatic parameters, not previously described in the literature. During the loading period, induced expression or accumulation of IL-6 and IL-8 in the interstitium was observed (p < 0.01). For IL-6, this upregulation was sustained for over 40 minutes post loading (p < 0.01). The same loading protocol was associated, through categorical analysis, with impaired lymph formation in lymphatic capillaries and disrupted valve function in collecting vessels directly under the load. The velocity of active lymphatic drainage along the loaded pathway was also significantly reduced (p < 0.05).The findings from this thesis support the proposal that impaired lymphatic function, with a corresponding accumulation of harmful biomolecules, are feasible mechanisms which can contribute to the development of pressure ulcers. The present study strongly supports further exploration of these hypotheses using the techniques described.

Text
Final Thesis 2018.03.05 - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: September 2017

Identifiers

Local EPrints ID: 420760
URI: http://eprints.soton.ac.uk/id/eprint/420760
PURE UUID: 403f990b-298f-4a66-ada2-3d070abf9542
ORCID for Daniel Bader: ORCID iD orcid.org/0000-0002-1208-3507
ORCID for David Voegeli: ORCID iD orcid.org/0000-0003-3457-7177

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Date deposited: 15 May 2018 16:30
Last modified: 14 Mar 2019 01:37

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