The role of peroneal nerve electrical neuromuscular stimulation in the augmentation of lower limb circulatory physiology in lower limb arterial and venous disease

Barnes, Rachel, M.D.

Medicine
December 2015

Thesis or dissertation


Rights
© 2015 MD Rachel Barnes. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Introduction:
Studies in healthy volunteers have demonstrated that peroneal nerve stimulation augments blood flow. The studies described within this thesis aimed to establish whether use of the geko™ neuromuscular stimulation device was effective and augments arterial venous and microcirculatory flow in patients with lower limb arterial and venous disease. The fibrinolytic and angiogenic activity of electrical stimulation within this cohort was also examined.

Methods:
Ethical approval was obtained for all aspects of the described studies. Participants with claudication, varicose veins or post- operative infrainguinal bypass grafts were assigned to receive either unilateral active stimulation or sham. Duplex assessments of arterial and venous volume flow were performed at baseline and following stimulation. Laser Doppler flowmetry measurements of microcirculatory flow were made continuously throughout the study period. ELISA analysis was undertaken of plasma samples drawn at baseline and following stimulation to determine the effect on vascular endothelial growth factor(VEGF), tissue plasminogen activator(t-PA) and plasminogen activator inhibitor 1(PAI-1).

Results:
The geko™ device was effective at producing visible muscle contraction in only 59% patients tested due to a combination of oedema and neuropathy. 77 participants were recruited in total to either a proof of concept study or the initial phase of a randomised trial: 30 claudicants (25 active, 5 control), 25 post infrainguinal bypass (19 active, 6 control) and 22 varicose veins (17 active, 5 control). Arterial volume flow increased significantly in all patient groups receiving active stimulation: claudicants 60 ml/ min(P<0.001); infra-inguinal bypass grafts 70ml/min(P<0.001) and varicose veins 80 ml/min(P<0.001). Venous volume flow significantly increased in all patient groups: claudicants 30 ml/min(P=0.001); infra-inguinal bypass grafts 30 ml/min(P=0.004) and varicose veins 80 ml/min(P<0.001).

Microcirculatory flow increased in all patient groups: claudicants 22.2 flux units(P<0.001); infra-inguinal bypass grafts 21.8 flux units(P<0.001) and varicose veins 28.4 flux units(P<0.001). ELISA analysis demonstrated no statistically significant change in VEGF or t-PA antigen levels when comparing the active with the passive and control limbs. Peroneal nerve stimulation in the active limbs resulted in a significant decrease in PAI-1 of 34 ng/ml(P<0.001).

Conclusion:
Transcutaneous peroneal nerve stimulation with the geko™ device is potentially beneficial in patients with lower limb arterial and venous disease. This is primarily due to its ability to augment venous, arterial and microcirculatory flow. The results of this study were influential in the NICE guidance approving its use in vascular patients as a means of DVT prophylaxis.

The enhanced fibrinolytic effect, by decreasing levels of PAI-1, warrants further investigation.

[Thesis also includes articles published in the following journals:
Blood coagulation & fibrinolysis: http://journals.lww.com/bloodcoagulation/Abstract/2016/04000/Fibrinolytic_effects_of_peroneal_nerve_stimulation.8.aspx
doi: 10.1097/MBC.0000000000000409

European journal of clinical investigation:
http://onlinelibrary.wiley.com/doi/10.1111/eci.12244/full
doi: 10.1111/eci.12244

Hypertension research:
http://www.nature.com/hr/journal/v36/n3/full/hr2012144a.html
doi:10.1038/hr.2012.144 ]

Publisher
Hull York Medical School, The University of Hull and the University of York
Supervisor
Chetter, Ian
Sponsor (Organisation)
Firstkind Ltd.
Qualification level
Doctoral
Qualification name
MD
Language
English
Extent
4 MB
Identifier
hull:14057
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