Vascular Dysfunction During Physical Inactivity

Not Applicable

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Reduced Activity	Step Count Reduction	Reduction of daily step count by 70% for two weeks, followed by two week recovery to normal activity level

Primary Outcome Measures

Name	Time	Method
Brachial Artery Vascular Function	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)	The flow rate of brachial artery measured by flow-mediated dilation (FDM). Doppler ultrasound will be used to determine brachial artery vascular function. Specifically, this assessment will include the measurement of flow rate and artery diameter at rest and in response to flow mediated dilation.

Secondary Outcome Measures

Name	Time	Method
Popliteal Artery Vascular Function	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)	Flow rate of popliteal artery measured by flow-mediated dilation (FMD). Doppler ultrasound will be used to determine popliteal artery vascular function. Specifically, this assessment will include the measurement of flow rate and artery diameter at rest and in response to flow mediated dilation.
Leg Microvascular Function	Baseline, during reduced activity (2 weeks) and 2 weeks post reduced activity (4 weeks)	Flow rate of leg microvasculature assessed by passive leg movement (PLM). Doppler ultrasound will be used to determine leg microvasculature function. Specifically, this assessment will include the measurement of flow rate at rest and in response to movement.