. Low-frequency oscillation of sympathetic nerve activity decreases during development of tiltinduced syncope preceding sympathetic withdrawal and bradycardia. Am J Physiol Heart Circ Physiol 289: H1758 -H1769, 2005. First published June 2, 2005; doi:10.1152/ajpheart.01027.2004.-Sympathetic activation during orthostatic stress is accompanied by a marked increase in low-frequency (LF, ϳ0.1-Hz) oscillation of sympathetic nerve activity (SNA) when arterial pressure (AP) is well maintained. However, LF oscillation of SNA during development of orthostatic neurally mediated syncope remains unknown. Ten healthy subjects who developed head-up tilt (HUT)-induced syncope and 10 agematched nonsyncopal controls were studied. Nonstationary timedependent changes in calf muscle SNA (MSNA, microneurography), R-R interval, and AP (finger photoplethysmography) variability during a 15-min 60°HUT test were assessed using complex demodulation. In both groups, HUT during the first 5 min increased heart rate, magnitude of MSNA, LF and respiratory high-frequency (HF) amplitudes of MSNA variability, and LF and HF amplitudes of AP variability but decreased HF amplitude of R-R interval variability (index of cardiac vagal nerve activity). In the nonsyncopal group, these changes were sustained throughout HUT. In the syncopal group, systolic AP decreased from 100 to 60 s before onset of syncope; LF amplitude of MSNA variability decreased, whereas magnitude of MSNA and LF amplitude of AP variability remained elevated. From 60 s before onset of syncope, MSNA and heart rate decreased, index of cardiac vagal nerve activity increased, and AP further decreased to the level at syncope. LF oscillation of MSNA variability decreased during development of orthostatic neurally mediated syncope, preceding sympathetic withdrawal, bradycardia, and severe hypotension, to the level at syncope. autonomic nervous system; baroreflex; blood pressure; heart rate variability; hemodynamics HUMANS HAVE BEEN SUBJECTED to ceaseless orthostatic stresses since they first evolved and assume an orthostatic posture for most of their lives. During standing, gravitational fluid shift toward the lower part of body (i.e., abdominal vascular bed and lower limbs) would cause severe orthostatic hypotension if it were not countered by compensatory mechanisms (23). Orthostatic sympathetic activation has a crucial role in preventing orthostatic hypotension and maintaining arterial blood pressure (AP) (23). Recent studies have reported that orthostatic sympathetic activation is accompanied by an increase in lowfrequency (LF, ϳ0.1-Hz) oscillation of sympathetic nerve activity (SNA) (1, 5). Tilt maneuvers of 75°and 80°greatly increase the LF oscillatory patterns of muscle SNA (MSNA), which mirrored similar changes in LF oscillation of AP (1, 5). However, LF oscillation of SNA has been investigated only in the steady-state orthostatic condition, when AP remains well maintained. It remains unclear whether LF oscillation of SNA changes during development of orthostatic neurally mediated s...