LIMB CONGESTION AND EXERCISE REFLEXES IN HEART FAILURE

Project: Research project

Description

The long-term objectives of the PI are to evaluate the mechanisms that regulate the circulatory system in humans. The specific aims of this project are to evaluate reflex responses to exercise in subjects with heart failure and in the aged. The key hypothesis underlying this proposal is that limb congestion secondary to increased venous pressure reversibly augments the discharge of mechanically-sensitive afferents in the skeletal muscle interstitium. We believe this augments the degree of sympathoexcitation during exercise in elderly subjects and those with heart failure. We speculate that limb congestion will increase and limb decongestion will reduce the level of muscle sympathetic nerve activity (MSNA; microneurography) seen during exercise. These effects will be independent of changes in limb blood flow that accompany limb congestion. Additionally, we speculate that the edematous state of heart failure will not augment the central volitional component of sympathoexcitation seen during exercise nor will it increase the contribution from metabolite-sensitive muscle afferents. Using an involuntary contraction model and an external compression paradigm, we believe we will show that mechanically-sensitive afferents are sensitized by limb congestion. We will also examine the effects of limb congestion on sympathetic nerve responses during forearm exercise in the aged. We anticipate that limb congestion in the aged will be associated with a prominent augmentation in the sympathetic response to exercise. Moreover responses to limb congestion in heart failure subjects will increase as a function of age. We speculate that this effect of limb congestion on sympathetic responses during exercise is not specific for heart failure and the aged. In an effort to test this hypothesis, we will examine the effects of lymphedema (secondary to mastectomy for breast cancer) on sympathetic discharge. We believe these studies will provide evidence that the magnitude of sympathetic discharge during exercise in elderly subjects and those with heart failure is in part mediated by the degree of interstitial fluid accumulation.
StatusFinished
Effective start/end date1/1/9512/31/03

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $281,015.00
  • National Institutes of Health: $35,129.00
  • National Institutes of Health: $276,998.00
  • National Institutes of Health: $273,093.00
  • National Institutes of Health
  • National Institutes of Health: $153,418.00
  • National Institutes of Health: $269,303.00

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Reflex
Extremities
Heart Failure
Exercise
Muscles
Forearm
Microdialysis
Peroneal Nerve
Skeletal Muscle
Investigative Techniques
Adenine Nucleotides
Quadriceps Muscle
Vasoconstrictor Agents
Protons
Venous Pressure
Lymphedema
Lactic Acid
Leg
Mastectomy
Extracellular Fluid