Intermittent claudication is a common condition affecting 5-10% of population over 65 years. Evidence supports a supervised exercise programme (SEP) as a clinically and cost effective treatment for claudication. However, the mechanisms by which these benefits are achieved remain unclear. The aim of this project is to investigate the mechanism by which SEP improves outcome in claudication.
Potential contributory factors include:
- Muscle fibre morphology; endurance increases proportion of slow type I aerobic fibres to fast type II anaerobic fibres and cell hypertrophy
- Cardiorespiratory physiology; The VO2 at the point of change from aerobic to anaerobic metabolism is termed the Ventilatory Anaerobic Threshold (VAT), and is an index used to estimate exercise capacity. Endurance training increases VO2 max and raises VAT
- Endothelial function; patients with IC have significant endothelial dysfunction. Exercise training augments nitric oxide dependant endothelial flow mediated vasodilatation.
- Thrombogenesis; moderate exercise (50-74% VO2max), suppresses platelet reactivity and enhances fibrinolysis.
- Angiogenesis; the development of collateral arterioles would appear angiographically to be an important mechanism by which exercise improves functional ability in IC.
In this study patients with intermittent claudication listed for surgical revascularisation will be randomised to a 4-week preoperative supervised exercise programme (SEP group) or usual care (control). Assessments will be performed at baseline, immediately preoperative and at 3, 6, and 12 months post revascularisation. They involve collaboration with Professor Khalid Naseem (Centre for Cardiovascular and Metabolic Research) in relation to thrombogenesis and platelet activation, and Dr Antonios Matsakas (Department of Sport, Health and Exercise Science) for assessment of muscle fibre morphology. The following outcomes will be measured:
a) Clinical indicators of lower limb ischaemia; patient reported walking distance, claudication and maximum walking distance (constant load treadmill 2.5km/hr with 10 degree incline), pre and post exercise ABPI.
b) Quality of life (Disease specific – VascuQol & Generic – SF36 & EQ5D)
c) Cardiopulmonary exercise testing – FEV1 & FVC; VO2 max & anaerobic threshold
d) Endothelial function – flow mediated vasodilatation
e) Intraoperative muscle biopsy- to assess architectural (fibre type, capillary density) and biochemical (mitochondrial density & activity)
f) Markers of angiogenesis- VEGF, TGF beta1, VCAM, Endothelial Progenitor cells.
g) Thrombogenesis – platelet activation, fibrinogen, vWF, tPA.
These measurements are aimed to provide insight into the mechanisms by which supervised exercise exerts an improvement in claudicants. This translational project aims to look at the spectrum of change that occurs from endothelial dysfunction at the capillary levels, the athero-inflammatory cascade through to the cardiac and respiratory changes. It also aims to identify the changes that occur in the muscle architecture secondary to exercise, and the markers of clinical improvement through the assessment of physical functional ability, walking distances and quality of life to allow a holistic picture of both the patient and pathophysiology.
Exercise classes are not widely available and do not improve outcomes in all patients. We remain uncertain how beneficial the class is, and whether more can be done to optimise it. We aim to identify the link between changes in muscle function and walking ability, so treatments can be personalised. This will be the first study to provide detailed multifaceted evidence regarding the relative importance of mechanisms by which exercise improves outcome in claudicants. This is important to patients, doctors and the NHS. It may also direct manipulation of supervised exercise programmes in order to maximise the effects of the most important mechanisms.
PhD students at HYMS have access to PGTS modules at the Universities of Hull and York for research modules and transferable skills development and gain a Masters level Certificate, or Diploma, in Research Training, in addition to their research degree.
:Prof Ian Chetter, Email: email@example.com
A full-time UK/EU PhD Scholarship will include fees at the ‘home/EU' student rate and maintenance (£13,726 in 2014/15, subject to final confirmation) for three years, depending on satisfactory progress. Full-time International Fee PhD Studentships will include full fees at the International student rate for three years, dependant on satisfactory progress, but no living expenses.
In order to qualify for this scholarship you will require a 2.1 in a relevant subject.
HOW TO APPLY
All applications MUST BE submitted to the HYMS Postgraduate Centre via the online application method: http://www.hyms.ac.uk/postgraduate/applying-for-postgraduate-study.aspx The deadline for applications is the 3rd February 2014.
Please quote PG201309 with the scholarship title when applying. In order for the Panel to get a sense of your academic background, commitment and interest, you are required to complete the application form in full and provide a research proposal/outline of academic interest. Research proposals and personal statements may be used in selecting applicants for interview. If you have any queries on how to apply please email firstname.lastname@example.org.
Please note that this is a student scholarship. If you will be employed by HYMS (e.g. on a fixed or short term contract) for the duration of your study, you will not be eligible to receive the student scholarship as a member of HYMS staff. You should contact Victoria Hill in Postgraduate Admissions if you still wish to apply to discuss different options.
The interview date for the scholarship has yet to be confirmed. Applicants who are short-listed for interview will be sent details of the date, time and venue via email. If you are not invited for the interview, it means that your application has not been successful. Please note that we do not offer feedback to applicants who are not invited to the interview.
As soon as reasonably practicable after the interviews have taken place HYMS will write to the successful applicant offering him/her the post. Upon receipt of formal written acceptance of the post we will write to notify unsuccessful candidates. Whilst we try to do this in as effective and efficient manner as possible, sometimes the process can take rather longer than is ideal because of the need to recall candidates for a second interview and reconvene interview panels and/or due to routine disruptions caused by leave and other absences. We apologise for any delay and inconvenience caused in these circumstances.