Exploring Time-efficient Strategies to Improve Fitness for Surgery in Older Adults (eHHH)

The incidence of conditions requiring surgical intervention increases with age, however there is a reported decline in the rates of elective surgical procedures in those over 65. This is associated with older patients being described as "less fit" and more at risk of postoperative complications, leading to decreased provision of surgical care to those at need. Exercise interventions have the potential to reverse some of the decline in cardiovascular fitness associated with aging and improve the elderly's' "fitness for surgery" and potentially allow increased access to surgical care for those most in need of it.

The percentage of people aged >65 y in the United Kingdom increased from 15% in 1985 to 17% in 2010, an increase of 1.7 million people. One age-associated physiological change is the reduction in vascular function that is observed, both at the levels of the large arteries and the muscle microvasculature. In itself this vascular dysfunction is associated with reduced aerobic performance. Cardiorespiratory fitness (marked by aerobic performance) has been shown to be an independent predictor of postoperative mortality, which provides more accurate prognostic information than age alone. In contrast, physical activity can reverse elements of pathophysiology associated with these conditions, including vascular dysfunction. Nonetheless, major roadblocks to exercise as a strategy to combat age-associated vascular dysfunction and associated conditions exist, namely: i) poor exercise tolerance, ii) "lack of time", iii) age-related mobility impairments, and iv) exercise resistance. The aim of this study is to investigate whether if novel low-volume, time-efficient training strategies can improve indices of vascular health and cardiorespiratory performance in older individuals with a view towards improving their fitness for surgery. Numerous studies have demonstrated that periods of supervised exercise training effectively improve indices of cardiorespiratory (blood pressure, aerobic capacity and blood lipids and vascular function. However, the majority of these studies were conducted using high-volume continuous submaximal aerobic training (e.g. 50-65% VO2max for 30-60 min) or moderate to high volume progressive weight training. This research group have recently shown the efficacy of a time-efficient exercise strategy known as HIIT - High Intensity Interval Training, for improving VO2 max and muscle mass in young individuals with heightened metabolic disease risk and also demonstrated significant improvements in VO2 max comparable to classic aerobic exercise training using several different time-efficient HIIT protocols. However, despite the potential benefits of HIIT, not least its 70-80% reduction in required time-commitment compared to current WHO guidelines, it does have limitations, particularly for an older population where physical (mobility/joint) and/or socio-economic (transport/gym access/equipment purchase) barriers may render it ineffective and/or unachievable. Alternative interventions for prevention or treatment of age-associated vascular dysfunction could be provided by isometric handgrip training (IHG) or remote ischaemic pre-conditioning (RIPC), both of which have a similar low time-commitment compared to HIIT but are less strenuous, have potential as home-based interventions, and require only inexpensive equipment. IHG has been demonstrated to improve resting blood pressure in both normotensive and medicated hypertensive populations to a similar or greater extent as classic aerobic exercise training. However, the effects of IHG on other vascular (e.g. limb, brain and muscle microvascular blood flow) or cardio-respiratory parameters (VO2 max, heart rate (resting/recovery), exercise tolerance) have not been assessed. Similarly, although RIPC has recently been shown to improve maximal athletic cardio-respiratory performance and vascular function in young subjects, no work to date has explored the efficacy of chronic RIPC on indices of health or vascular function in older individuals. Therefore, the aims of this project are to: (i) Assess the efficacy of 6 weeks HIT, IHG and RIPC for improving indices of cardio-respiratory, vascular and metabolic function in older subjects as a means of improving fitness for surgery. (ii) Explore the concept of "exercise resistance" in relation to HIT, IHG and RIPC by: Assessing if the same degree of response heterogeneity exists for the three time-efficient training modes employed in this study as has been reported for classic resistance and aerobic exercise training Assessing if a "non-responder" for one index (i.e., resting blood pressure or leg blood flow) is a non-responder for all other indices

3 x 15 minute sessions per week for 6 weeks. Sessions include 5x intervals of cycling at 110% of Wmax derived from CPET, interspersed with 90s rest periods of unloaded cycling.

3x 15 minute sessions per week for 6 weeks Sessions include 4x intervals of 2minutes isometric handgrip contraction of dominant arm at 30% Maximal voluntary contraction, interspersed with 2minute rest periods

3x 15 minute sessions per week for 6 weeks. Sessions include 3x intervals of 3 minutes of arm ischaemia (blood pressure cuff inflated to 200mmHg on dominant arm) interspersed with 3 minute rest periods.

Measured in seated position using oscillometry, mean value of 3 recordings, measured according to British Society of Hypertension Guidelines 2013.

Measured by duplex ultrasound on non-dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum

Measured by contrast enhanced ultrasound on the dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum

Inclusion Criteria: Healthy volunteer aged 65-85 Exclusion Criteria: • Current participation in a formal exercise regime A BMI < 18 or > 32 kg·m2 Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), Significant arrhythmia, right to left cardiac shunt, recent cardiac event Taking beta-adrenergic blocking agents, Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial) epilepsy Respiratory disease including: pulmonary hypertension, Significant COPD, Uncontrolled asthma, Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, type 1 or 2 diabetes Active inflammatory bowel or renal disease Malignancy Clotting dysfunction Significant Musculoskeletal or neurological disorders Family history of early (<55y) death from cardiovascular disease Known sensitivity to Sonovue

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http://webarchive.nationalarchives.gov.uk/20160105160709/http://www.ons.gov.uk/ons/dcp171776_258607.pdf

Office for National Statistics; Population Ageing in the United Kingdom, its Constituent Countries and the European Union