Creatine Use and Muscle Stretching in Peripheral Artery Disease

To utilize near-infrared spectroscopy to investigate if the research device, which induces muscle stretching, and creatine loading impact submaximal exercise performance in aged and PAD patients. Near-infrared spectroscopy (NIRS)-derived tissue oxygenation responses will be obtained during device placement (muscle stretch) and during a walking test (i.e., six-minute walk test). Muscle oxygenation at rest and during device placement will be assessed with Magnetic Resonance Imaging. It is hypothesized that the stretching protocol will improve both NIRS-derived tissue oxygenation and magnetic resonance-derived muscle oxygenation and that creatine supplementation will further improve phosphorus metabolite muscle performance. All patients will undergo either 4 weeks of stretch training with- or- without creatine supplementation according to previously defined creatine guidelines.

Lower extremity peripheral artery disease (PAD) has been estimated to impact nearly 8.5 million U.S. adults above the age of 40, significantly increasing the rate of morbidity and mortality with concomitant decreases in quality of life. These patients are often given medical therapy (e.g., statins, antiplatelet, anticoagulants) and are also recommended to begin structured exercise programs. However, the limb ischemia that occurs during physical activity in these patients often limits exercise tolerance. A previous study by Bauer and colleagues showed that impaired muscle metabolism is a major contributor to functional limitations in PAD patients. These data are important in that they show alterations in blood flow and metabolic machinery likely impact exercise tolerance. As such, the development of tolerable countermeasures to improve limb blood flow and muscle energetics may increase adherence to exercise therapy and improve health outcomes in PAD patients. Previous work by the investigators has shown that daily muscle stretching, achieved via 30-minutes of ankle dorsiflexion, significantly improved soleus muscle function and muscle blood flow during exercise in a rat model of aging . In a follow-up study, the investigators have also shown that this model improves vascular function and walking function in PAD patients. As noted above, muscle energetics are delayed in PAD patients, so improving the rest-to-exercise transition with creatine supplementation may help PAD patients sustain exercise longer. The investigators are now testing to see if an added supplement can further improve the effects of muscle stretching in PAD patients.

Creatine Monohydrate will be given at a 5 day loading period (10g/day) followed by a maintenance phase (5 g/day). The objectives of the current trial are to investigate if creatine supplementation plus muscle stretching improves 6-minute walking distance and muscle oxygenation in patients with peripheral artery disease.

These participants will consume a fiber supplement in place of creatine monohydrate at a matched dose with muscle stretching.

All patients will perform a pre -and -post 6 minute walking test to assess functional outcomes of muscle stretching and supplementation

Use of NIRS on the lateral head of the gastrocnemius muscle in all patients will be performed. NIRS will be measured during a vascular occlusion test, during placement of splint device, and the 6 minute walking test.

Use of MRI to assess muscle oxygenation during a vascular occlusion test at rest, and during placement of splint device

Inclusion Criteria: Ankle-brachial index (ABI) of 0.90 or less in either leg or clinical diagnosis by a medical doctor (PAD group only) Stable condition for at least 3 months (PAD group only) Exclusion Criteria: Habitual exercise or cardiovascular rehabilitation program during the past 3 months Critical limb ischemia Blow or above-knee amputation Leg pain at rest Major surgery or lower extremity revascularization in the last 3 months Major medical illness treatment during the prior 12 months Central neurological disease Limited ankle or knee joint range of motion Requirement of oxygen with activity or exercise Heart failure Atrial fibrillation Wheelchair confinement or inability to walk Cognitive disorder Vasculitis problems including Takayasu's arteritis, Berger's disease, collagen disease or Reynaud's disease Overt cardiovascular disease Metabolic disease Renal disease

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