Abstract 618: Sympathetic Nervous System-Mediated Low Frequency Fluctuations in Blood Pressure are Independent of Baroreflex Modulation in Autonomic Failure

Abstract

Autonomic cardiovascular regulation involves sympathetic rhythms that contribute to blood pressure fluctuations in the low frequency range. It has been suggested that fluctuations in sympathetic vasomotor tone reflect a resonance phenomenon due to interplay between the vasculature and baroreflex. Alternatively, this could reflect an intrinsic rhythm of pacemaker neurons. To dissect the autonomic origin of this cardiovascular rhythm, we studied autonomic failure patients with loss of baroreflex buffering. We hypothesized that if this rhythm originates in pacemaker neurons, it would be present in multiple systems atrophy (MSA) patients in whom residual sympathetic tone is intact but not regulated by the baroreflex, and absent in pure autonomic failure (PAF) patients with postganglionic sympathetic denervation. We studied 28 MSA and 34 PAF patients with severe autonomic impairment and neurogenic orthostatic hypotension. Low-frequency systolic blood pressure variability (LFSBP), an index of sympathetic modulation of vasomotor tone, and baroreflex sensitivity (BRS) were assessed by spectral analysis of continuous blood pressure and heart rate recordings. MSA patients had higher LFSBP during supine rest compared with PAF patients (3.3±0.5 versus 1.5±0.2 mmHg2, respectively; p=0.003), despite similarly low BRS (3.6±0.6 PAF versus 4.3±0.7 msec/mmHg MSA; p=0.380). LFSBP was higher in MSA patients with supine hypertension compared with normotensive patients (4.1±0.6 versus 2.3±0.6 mmHg2; p=0.041), with no differences in PAF patients (1.5±0.2 hypertensive versus 1.6±0.3 mmHg2 normotensive, respectively; p=0.984). These findings suggest that LFSBP is driven by an intrinsic rhythm originating in central sympathetic pathways in MSA patients, independent of baroreflex-mediated blood pressure fluctuations. The precise origin of this rhythm is unclear but may include central pacemaker neurons, spinal cord neurons or loops, or hormonal mechanisms. In addition, LFSBP is higher in MSA patients with sympathetically-mediated hypertension, but low and fixed in PAF patients with sympathetic-independent hypertension. Overall, these findings provide new insight into neural regulatory mechanisms involved in blood pressure control.