The effects of antioxidants on health and exercise ability in individuals with peripheral artery disease.

INTERVENTION: Intravenous infusion of an antioxidant glutathione will be performed on one occasion. Rate of infusion will be 15 mg/min over 4 hours (approximately 3600mg). The infusion will be ongoing during the exercise test. Outcome measures will be measured at baseline, after 1 hour of infusion (pre‐exercise), immediately post an acute exercise bout and 30 minutes after exercise. These measures will be conducted in the Exercise Science Laboratory at Deakin University, Burwood by research staff who are members of the research team and are trained in cannulation and first aid. The exercise bout will be a single maximal exercise test performed on a treadmill in a one‐on‐one scenario. This exercise will be performed approximately 60 minutes after the infusion is commenced. The exercise test will be supervised by a minimum of two first aid trained and experienced research team members. The test is completed at 3.2 km/h and begins at a grade of 0% for the first 5 minutes and then is increased by 3.5% every 3 minutes until subjects reach their maximum exercise capacity. Alternatively, we will use the graded Gardner‐Skinner treadmill exercise test which is a well‐accepted modified‐load treadmill exercise test that is frequently used in randomized trials of therapeutic interventions in PAD. In this protocol, participants begin walking on the treadmill at 2.0 mph with a grade of zero. The treadmill speed is maintained at 2.0 mph throughout testing, and the treadmill grade is increased by 2% every 2 minutes. Participants with PAD who are unable to walk at 2.0 mph should perform a modified Gardner treadmill test in which the speed begins at 0.5 mph and a grade of zero and speed is increased by 0.5 mph every 2 minutes until 2.0 mph is achieved. When a speed of 2.0 mph is reached, CONDITION: Cardiovascular ‐ Other cardiovascular diseases peripheral artery disease; ; peripheral artery disease PRIMARY OUTCOME: Cardiorespiratory fitness/exercise capacity.; ; Cardiopulmonary exercise test: Participants will undergo a graded exercise test to exhaustion on a cycle ergometer to determine exercise capacity using standard clinical exercise testing and indirect calorimetry equipment.[60 minutes after infusion is commenced, at the beginning of the maximal exercise test.] INCLUSION CRITERIA: INCLUSION CRITERIA: Aged 40‐75 y, BMI less than or equal to 35 kg/m2, ankle brachial inde X(ABI) of less than or equal to 0.90. SECONDARY OUTCOME: Cardiac function will be assessed via echocardiographic assessment using a commercial ultrasound machine. [Baseline, pre‐exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.] Cerebral blood flow will be measured via transcranial Doppler and duple Xultrasound.[Baseline, pre‐exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.] Femoral arterial diameter and blood velocity will be assessed using 2D and Doppler ultrasound imaging. This will be assessed as a composite outcome.[Baseline, pre‐exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.] Microvascular blood flow will be measured in the thigh via contrast enhanced ultrasound imaging during contrast agent infusion.[Pre‐exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.]