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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG012227-06
Application #
6137042
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Nayfield, Susan G
Project Start
1995-01-01
Project End
2003-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
6
Fiscal Year
2000
Total Cost
$269,303
Indirect Cost
Name
Pennsylvania State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Momen, Afsana; Bower, Douglas; Leuenberger, Urs A et al. (2005) Renal vascular response to static handgrip exercise: sympathetic vs. autoregulatory control. Am J Physiol Heart Circ Physiol 289:H1770-6
Sinoway, Lawrence I; Li, Jianhua (2005) A perspective on the muscle reflex: implications for congestive heart failure. J Appl Physiol 99:5-22
Momen, Afsana; Leuenberger, Urs A; Handly, Brian et al. (2004) Effect of aging on renal blood flow velocity during static exercise. Am J Physiol Heart Circ Physiol 287:H735-40
Lott, Mary E J; Herr, Michael D; Sinoway, Lawrence I (2004) Effects of age on brachial artery myogenic responses in humans. Am J Physiol Regul Integr Comp Physiol 287:R586-91
Samii, Soraya; Khan, Mazhar H; MacLean, David A et al. (2004) Muscle interstitial calcium during head-up tilt in humans. Circulation 109:215-9
Imadojemu, Virginia A; Mooney, Kenneth; Hogeman, Cindy et al. (2004) Extracellular calcium and vascular responses after forearm ischemia. Circulation 110:79-83
Momen, Afsana; Bower, Douglas; Boehmer, John et al. (2004) Renal blood flow in heart failure patients during exercise. Am J Physiol Heart Circ Physiol 287:H2834-9
Momen, Afsana; Leuenberger, Urs A; Ray, Chester A et al. (2003) Renal vascular responses to static handgrip: role of muscle mechanoreflex. Am J Physiol Heart Circ Physiol 285:H1247-53
Leuenberger, Urs A; Mostoufi-Moab, Sogol; Herr, Michael et al. (2003) Control of skin sympathetic nerve activity during intermittent static handgrip exercise. Circulation 108:2329-35
Daley 3rd, Joseph C; Khan, Mazhar H; Hogeman, Cynthia S et al. (2003) Autonomic and vascular responses to reduced limb perfusion. J Appl Physiol 95:1493-8

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