Vascular Dysfunction During Physical Inactivity

Study Overview
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Brief Summary
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Prolonged periods of reduced activity are associated with decreased vascular function and muscle atrophy. Physical inactivity due to a sedentary lifestyle or acute hospitalization is also associated with impaired recovery, hospital readmission, and increased mortality. Older adults are a particularly vulnerable population as functional (vascular and skeletal muscle mitochondrial dysfunction) and structural deficits (loss in muscle mass leading to a reduction in strength) are a consequence of the aging process. The combination of inactivity and aging poses an added health threat to these individuals by accelerating the negative impact on vascular and skeletal muscle function and dysfunction. The underlying factors leading to vascular and skeletal muscle dysfunction are unknown, but have been linked to increases in oxidative stress. Additionally, there is a lack of understanding of how vascular function is impacted by inactivity in humans and how these changes are related to skeletal muscle function. It is the goal of this study to investigate the mechanisms that contribute to disuse muscle atrophy and vascular dysfunction in order to diminish their negative impact, and preserve vascular and skeletal muscle function.

Official Title
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Vascular Dysfunction During Physical Inactivity: Role of Oxidative Stress

Conditions
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Aging, Vascular Endothelium, Skeletal Muscle

Intervention / Treatment
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* Behavioral: Step Count Reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who have recently undergone surgery or injury requiring inactivity Exclusion Criteria: Cardiac abnormalities considered exclusionary by the study physician (congestive heart failure, coronary artery disease, right-to-left shunt) Uncontrolled endocrine or metabolic disease Glomerular filtration rate < 45 mL/min/1.73 m^2 or evidence of kidney disease or failure Vascular disease or risk factors of peripheral atherosclerosis Risk of deep vein thrombosis including family history of thrombophilia, pulmonary emboli, deep vein thrombosis Use of anticoagulant therapy Elevated systolic pressure > 180 or a diastolic blood pressure > 110 Implanted electronic devices such as pacemakers, infusion pumps, stimulators Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma Currently on a weight-loss diet or body mass index > 35 kg/m^2 Inability to abstain from smoking for duration of study History of > 20 pack per year smoking Positive for human immunodeficiency virus, hepatitis B or hepatitis C Recent anabolic or corticosteroids use (within 3 months) Subjects with hemoglobin or hematocrit lower than accepted lab values Agitation/aggression disorder History of stroke with motor disability Recent history (< 12 months) of gastrointestinal bleed Depression diagnosis Alcohol or drug abuse Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia) Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation < 97% on room air) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Activity<br>Reduction of daily step count by 70% for two weeks | Behavioral: Step Count Reduction<br>* Subjects reduce daily step counts by approximately 70% through monitoring and recording from step-count monitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial artery vascular function | Flow rate of brachial artery measured by flow-mediated dilation | 2 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Popliteal artery vascular function | Flow rate of popliteal artery measured by flow-mediated dilation | 2 Weeks | 
| Leg microvascular function | Flow rate of leg microvasculature assessed by passive leg movement and measured by flow-mediated dilation | 2 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reduced Activity, Muscular Atrophy, Vascular Dysfunction