Spectral analysis of the RR interval has shown distinct oscillations at q0.1 Hz (low frequency-LF) and q0.25 Hz (high frequency-HF). The LF is loosely considered to be a marker of sympathetic modulation of RR interval. The HF component, synchronous with respiration, is loosely considered a marker of vagal modulation of heart rate. There is surprisingly little evidence to justify these assumptions. This proposal demonstrates that LF and HF oscillations are clearly present in direct intraneural recordings of sympathetic nerve activity to both muscle blood vessels and skin blood vessels in humans. These oscillations in neural activity are closely coherent with similar oscillations in RR interval and intra-arterial blood pressure. Modulation of the LF and HF oscillations in muscle sympathetic nerve activity (MSNA), skin sympathetic nerve activity, RR interval and blood pressure in response to changes in the balance between sympathetic and vagal drive will be defined; first, during changes in autonomic balance induced by nitroprusside (to increase sympathetic drive) and phenylephrine (to increase vagal drive); second, during sympathetic inhibition in nonREM sleep and sympathetic activation in REM sleep; and third, with low dose atropine to increase vagal tone and high dose atropine to elicit vagal blockade. Further, using 6 repeated measurements over 6 months it will be determined whether spontaneous fluctuations in RR interval, blood pressure and MSNA are accompanied by systematic changes in the balance between LF and HF oscillations. Thus, the hypothesis that increased vagal tone is accompanied by a dominance of HF oscillation of cardiovascular variability, and that increased sympathetic drive is accompanied by a relative dominance of the LF oscillations will be tested. These oscillations will also be examined in heart failure, a condition in which there is very high sympathetic drive to the heart and blood vessels, and in patients after cardiac transplantation. Studies in normal subjects during apnea, and in patients with left ventricular assist devices, will test the hypothesis that the LF and HF oscillations have a central neural origin. These studies will add an important and novel dimension to our understanding of central mechanisms regulating autonomic function.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
International Research Fellowships (FIC) (F05)
Project #
7F05TW005399-02
Application #
6152726
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Project Start
1999-09-30
Project End
Budget Start
1999-09-29
Budget End
2000-09-28
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Winnicki, Mikolaj; Shamsuzzaman, Abu; Lanfranchi, Paola et al. (2004) Erythropoietin and obstructive sleep apnea. Am J Hypertens 17:783-6
Winnicki, Mikolaj; Accurso, Valentina; Hoffmann, Michal et al. (2004) Physical activity and angiotensin-converting enzyme gene polymorphism in mild hypertensives. Am J Med Genet A 125A:38-44
Shamsuzzaman, Abu S M; Winnicki, Mikolaj; Wolk, Robert et al. (2004) Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109:2181-5
Winnicki, Mikolaj; Somers, Virend K; Accurso, Valentina et al. (2002) alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity. J Hypertens 20:1771-7
Winnicki, Mikolaj; Somers, Virend K; Accurso, Valentina et al. (2002) Fish-rich diet, leptin, and body mass. Circulation 106:289-91
Winnicki, M; Phillips, B G; Accurso, V et al. (2001) Independent association between plasma leptin levels and heart rate in heart transplant recipients. Circulation 104:384-6
Accurso, V; Winnicki, M; Shamsuzzaman, A S et al. (2001) Predisposition to vasovagal syncope in subjects with blood/injury phobia. Circulation 104:903-7