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.
| 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 |
| 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 |
| Markel, Troy A; Daley 3rd, Joseph C; Hogeman, Cynthia S et al. (2003) Aging and the exercise pressor reflex in humans. Circulation 107:675-8 |
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