Does a supervised exercise program for claudication have an adverse effect on muscle, endothelial and immune function?

Author: Simon Vun

Vun, Simon, 2020 Does a supervised exercise program for claudication have an adverse effect on muscle, endothelial and immune function?, Flinders University, College of Medicine and Public Health

Terms of Use: This electronic version is (or will be) made publicly available by Flinders University in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. You may use this material for uses permitted under the Copyright Act 1968. If you are the owner of any included third party copyright material and/or you believe that any material has been made available without permission of the copyright owner please contact with the details.


Supervised exercise therapy has become increasingly engrained as the first-line treatment for patients who suffer from intermittent claudication. This is on the basis of a large body of clinical studies and meta-analysis, demonstrating significant and meaningful gains in walking distance, together with the suboptimal long-term results of medications and invasive treatment.

There is, however, a concern from some authorities, that the exercise may promote injury to physiological systems and potentially lead to adverse effects for patients. One hypothesis suggests that repeated exposure to the ischaemia- reperfusion phenomenon, which is intentionally provoked by exercise therapy, may lead to adverse consequences for muscle, endothelial or immune function; this is the focus of this thesis.

An adverse effect on muscle mass had previously been reported in a study of patients completing treadmill-training and thus, the first focus of this thesis was to determine where in the lower-limb this was actually taking place.

Firstly, an original analysis protocol to quantify lower limb regional muscle mass using DEXA was developed and demonstrated to be reliable on repeated measures. Secondly, this protocol was applied to a group of patients with claudication before and following completion of 12-weeks of supervised exercise therapy. It was hypothesised that a decrease in muscle mass might be observed in the symptomatic and ischaemic muscle as a result of training. Unexpectedly, there was no change in muscle mass in the symptomatic part of the leg, but there was a significant decrease in muscle mass of the thigh. Whilst reassuring that the ischaemia-reperfusion, that exercising patients with claudication are exposed to, does not result in calf muscle atrophy, this finding has generated more questions as to why and how thigh musculature is affected, and whether this is an adverse effect.

Thirdly, this thesis sought to determine if the 12-week supervised exercise program had any effect on endothelial function assessed by a number of means. A number of small non-protein coding RNA molecules, known as microRNAs, have been increasingly implicated in cardiovascular pathophysiology. One microRNA in particular, miR-92a, appears to have a central role in endothelial dysfunction, vascular inflammation and response to ischaemic injury. microRNA-92a expression, determined by quantitative PCR, was measured from blood, and skeletal muscle biopsies, together with other markers of endothelial function, flow-mediated dilation, and peripheral artery tonometry. Whilst no change was seen in the latter two measures, microRNA-92a levels were lower following 12- weeks of training, suggesting a positive effect of exercise. This study also reports on the levels of an additional measure of endothelial dysfunction, endocan measured by ELISA, which was elevated in patients with claudication compared to healthy controls.

In addressing the question of the effects of supervised exercise on the immune system, inflammatory monocyte subtypes and CD16 expression were assessed by flow cytometry in healthy controls and patients with claudication following 12- weeks of supervised treadmill training. It was observed that patients with claudication have higher numbers of total and inflammatory monocytes, compared to unselected controls, but this was not affected by training. It was, however, observed that monocyte CD16 expression reduced following the exercise training, again possibly suggesting a positive effect of training in the immune system

Finally, it was again observed that treadmill training results in a significant improvement in walking performance in an overground 6-minute walk test.

Thus, the present collection of studies in this thesis, does not suggest there is an adverse effect on calf muscle, endothelial or monocyte function. Whether the changes in thigh muscles are adverse is so far unknown. The long-term effects are as yet unknown, as the possible difference to home- or land-based training, which should be a focused as part of future study.

Keywords: intermittent, claudication, peripheral artery, disease, vascular, muscle, DEXA, microRNA

Subject: Surgery thesis

Thesis type: Masters
Completed: 2020
School: College of Medicine and Public Health
Supervisor: Dr Christopher Delaney