Project: Research project

Project Details


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
Effective start/end date1/1/9512/30/95


  • National Institute on Aging

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