Muscle Perfusion and Protein Metabolism in Elderly

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-05-31

Study Completion Date

2009-05-31

Brief Summary

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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.

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Detailed Description

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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).

Conditions

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Aging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Blinding Strategy

NONE

Study Groups

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Young Aerobic Exercise

45 minutes of treadmill walking at 40% VO2 peak

Group Type ACTIVE_COMPARATOR

Aerobic Exercise

Intervention Type OTHER

45 minuties of treadmill walking was completed at 40% VO2 peak

Elderly Aerobic Exercise

45 minutes of treadmill walking at 40% VO2 peak

Group Type ACTIVE_COMPARATOR

Aerobic Exercise

Intervention Type OTHER

45 minuties of treadmill walking was completed at 40% VO2 peak

Young Sodium Nitroprusside

Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Group Type ACTIVE_COMPARATOR

Sodium Nitroprusside

Intervention Type DRUG

Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Elderly Sodium Nitoprusside

Sodium Nitroprusside given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Group Type ACTIVE_COMPARATOR

Sodium Nitroprusside

Intervention Type DRUG

Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

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

Group Type ACTIVE_COMPARATOR

Sodium Nitroprusside

Intervention Type DRUG

Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Amino Acid Drink

Intervention Type DIETARY_SUPPLEMENT

7.5 gram Amino Acid drink

Interventions

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Aerobic Exercise

45 minuties of treadmill walking was completed at 40% VO2 peak

Intervention Type OTHER

Sodium Nitroprusside

Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Intervention Type DRUG

Amino Acid Drink

7.5 gram Amino Acid drink

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Nitropress

Eligibility Criteria

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Inclusion Criteria

1. Age: young 18-40 yrs; elderly 60-85 yrs.
2. Availability of transportation (i.e., subjects must be able to provide their own transportation to UTMB).
3. Ability to sign informed consent (score \>24 on 30 item mini-mental status exam and no errors on assessment of judgment).

Exclusion Criteria

1. 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.
2. Any patient with atrial fibrillation, history of syncope, angina, or congestive heart failure.
3. 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).
4. Peripheral vascular disease as determined by history or abnormal ankle-brachial index by Doppler (\< 1.0).
5. 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.
6. Any person HIV-seropositive, with active hepatitis, or any other immunosuppressive or autoimmune disease.
7. Any patient taking beta blockers, vasodilators, angiotensin-converting enzyme inhibitors, calcium channel blockers, or alpha blockers.
8. Any patient with uncontrolled metabolic diseases including any patient with liver or renal disease.
9. 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).
10. Currently in muscle strengthening program.
11. Total knee replacement or moderate to severe degenerative joint disease of knees.
12. Anemia (hemoglobin \<13 g/dL in males or \<12 g/dL in females).
13. Any history of hypo- or hyper-coagulation disorders, including patients taking Coumadin or with a history of deep venous thrombosis (DVT) or pulmonary embolism (PE) at any point in their lifetimes.
14. Currently taking aspirin and cannot stop for 7 days (i.e., medical indication for continued aspirin such as transient ischemic attacks).
15. Presence of acute illness or metabolically unstable chronic illness.
16. Heart disease requiring therapy or recent myocardial infarction (less than 1 year)
17. Currently on weight-loss diet.
18. Active cancer or in short-term remission (less than 3 years).
19. Alcohol or drug abuse.
20. History of \>20 packs per year cigarette smoking.
21. Recent (within 6 months) ingestion or injection or transdermal administration of anabolic steroids, corticosteroids, estrogens, or progestagens.
22. History of falls (1 fall in the past year which required medical attention, or more than 2 falls/year regardless of severity).
23. Allergy to iodides, penicillin or shellfish.
24. Any subject with a know hypersensitivity to octafluoropropane.
25. Any subject with a cardiac shunt.
26. Any subject with chronic obstructive pulmonary disease (COPD).

Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes