A Phase I Trial Examining Muscle Perfusion and Protein Metabolism in Elderly and Young
Overview
- Phase
- Phase 1
- Intervention
- Aerobic Exercise
- Conditions
- Aging
- Sponsor
- The University of Texas Medical Branch, Galveston
- Enrollment
- 62
- Primary Endpoint
- Mixed Muscle Fractional Synthesis Rate (FSR)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study was to examine the role skeletal muscle perfusion plays in mediating muscle protein synthesis in healthy older and younger individuals. The investigators hypothesized that normalization of muscle perfusion in older men and women via exercise or infusion of a vasodilator would enhance nutritive flow and skeletal muscle protein synthesis in the elderly similar to that of their younger counterparts.
Detailed Description
The purpose of this study was to examine muscle protein metabolism in healthy young and elderly subjects during pharmacologic vasodilation of the lower limb vasculature in combination with increased amino acids delivery. We obtained femoral arteriovenous blood samples and v. lateralis muscle biopsies during a primed continuous infusion of L-\[ring-13C6\] Phenylalanine. Muscle protein kinetics were measured in the basal state and during a 180 min infusion of sodium nitroprusside (SNP) and amino acids (Premsol 10%) (SNP+AA). Skeletal muscle microvascular recruitment and flow were measured during the basal state and SNP+AA using contrast-enhanced ultrasound (CEU).
Investigators
Eligibility Criteria
Inclusion Criteria
- •All inclusion criteria must be fulfilled throughout the study. At enrollment, subjects must fit the following criteria:
- •Age: young 18-40 yrs; elderly 60-85 yrs.
- •Availability of transportation (i.e., subjects must be able to provide their own transportation to UTMB).
- •Ability to sign informed consent (score \>24 on 30 item mini-mental status exam and no errors on assessment of judgment).
Exclusion Criteria
- •None of the following exclusion criteria should be present at enrollment or throughout the study:
- •Patients with limiting or unstable angina or who demonstrate cardiac abnormalities such as \> 0.2 mV horizontal or downsloping ST segment depression, frequent arrhythmias (\>10 PVC/min), or valvular disease.
- •Any patient with atrial fibrillation, history of syncope, angina, or congestive heart failure.
- •Patients with vascular disease, as determined by the presence of risk factors of peripheral atherosclerosis (i.e., hypertension, obesity, uncontrolled diabetes, and evidence of venous or arterial insufficiency upon palpation of femoral, popliteal, and pedal arteries).
- •Peripheral vascular disease as determined by history or abnormal ankle-brachial index by Doppler (\< 1.0).
- •Any subject with blood pressure on three consecutive measurements taken at rest on separate occasions that has a systolic pressure \>170 mm Hg or a diastolic blood pressure \>100 mm Hg will be excluded. Subjects will not be included if they are taking blood pressure medication and have a blood pressure above these criteria.
- •Any person HIV-seropositive, with active hepatitis, or any other immunosuppressive or autoimmune disease.
- •Any patient taking beta blockers, vasodilators, angiotensin-converting enzyme inhibitors, calcium channel blockers, or alpha blockers.
- •Any patient with uncontrolled metabolic diseases including any patient with liver or renal disease.
- •Glucose intolerance: fasting plasma glucose concentration 110-126 mg/dL (6.1-7 mmol/L) and/or 2-h plasma glucose 140-200 mg/dL (7.8-11.1 mmol/L) during oral glucose tolerance test (OGTT).
Arms & Interventions
Young Aerobic Exercise
45 minutes of treadmill walking at 40% VO2 peak
Intervention: Aerobic Exercise
Elderly Aerobic Exercise
45 minutes of treadmill walking at 40% VO2 peak
Intervention: Aerobic Exercise
Young Sodium Nitroprusside
Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min
Intervention: Sodium Nitroprusside
Elderly Sodium Nitoprusside
Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min
Intervention: Sodium Nitroprusside
Elderly Sodium Nitroprusside and Amino Acid Drink
Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min and 7.5g amino acid drink taken orally
Intervention: Sodium Nitroprusside
Elderly Sodium Nitroprusside and Amino Acid Drink
Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min and 7.5g amino acid drink taken orally
Intervention: Amino Acid Drink
Outcomes
Primary Outcomes
Mixed Muscle Fractional Synthesis Rate (FSR)
Time Frame: Acute ( 8 hours)
The rate at which the body makes new muscle was assessed by determining the fractional synthesis rate (FSR). This technique determines how quickly new amino acids are used to make muscle. In this technique, a special (but natural and non-radioactive) version of an amino acid is infused into the blood. This special version of the amino acid is heavier than the most common version the same amino acid. This property allows it to be identified in a muscle sample. By determining how much of the special amino acid has accumulated over time in a muscle sample, the fractional synthesis rate can be determined. For example, if the rate were such that 1 of every 100 amino acids were of the special type after 1 day, the fractional synthesis rate would be 1% per day. In other words, 1/100 of the muscle would be newly made each day.