Project: Research project

Project Details


DESCRIPTION (Applicant's abstract): The long-range goals of the PI are
to evaluate the mechanisms that regulate blood flow delivery in heart
failure. The short-range goals are to determine: 1) the interstitial
metabolites that may evoke the muscle metaboreflex in heart failure, and
2) the effects of exercise conditioning on reflex responses to exercise
in heart failure. Recent work from our laboratory has suggested that the
muscle metaboreflex is engaged at low levels of rhythmic forearm
exercise in heart failure patients. This premature reflex engagement was
associated with increased sympathetic drive directed to inactive
skeletal muscle. To date no one has characterized the interstitial
concentrations of the many muscle metabolites that may be responsible
for engaging this reflex in normal subjects and those with heart
failure. We have begun using the microdialysis method to directly
determine interstitial concentrations of multiple potential
metaboreceptor stimulants in humans. We have spent a great deal of
effort over the last few years modifying microdialysis methods so that
we can now measure lactate, phosphate, adenosine, potassium and hydrogen
ion in the interstitium of resting and exercising skeletal muscle. In
this proposal we will utilize this method during rhythmic quadriceps
contractions in subjects with heart failure and in aged-matched and
young controls as we simultaneously measure opposite leg muscle
sympathetic nerve activity (MSNA). We hypothesize that K+ and phosphate
will correlate best with MSNA. We will then examine the effects of
quadriceps muscle conditioning on muscle metaboreflex activity. In
separate studies, we will compare the effects of ischemic and non-
ischemic conditioning on the muscle reflex in the three subject groups
discussed above. We speculate that conditioning will increase limb blood
flow, reduce metabolite production and in the process reduce MSNA
responses to quadriceps contractions more in heart failure subjects than
in controls. We speculate that ischemic forearm training will serve as
a potent stimulus to attenuate MSNA in the peroneal nerve and
vasoconstrictor influences in the exercising forearm. Novel components
of the work described include the use of multiple state of the art human
investigative techniques including microdialysis, peroneal nerve
recordings of sympathetic traffic, Doppler flow measurements, 31P NMR
spectroscopy, and the use of ischemic and non-ischemic exercise
conditioning paradigms. To our knowledge studies such as these have not
been previously performed.
Effective start/end date1/1/9512/31/03


  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging: $269,303.00


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