Muscle sympathetic nerve activity during intense lower body negative pressure to presyncope in humans

Abstract

Activation of sympathetic efferent traffic is essential to maintaining adequate arterial pressures during reductions of central blood volume. Sympathetic baroreflex gain may be reduced, and muscle sympathetic firing characteristics altered with head-up tilt just before presyncope in humans. Volume redistributions with lower body negative pressure (LBNP) are similar to those that occur during haemorrhage, but limited data exist describing arterial pressure-muscle sympathetic nerve activity (MSNA) relationships during intense LBNP. Responses similar to those that occur in presyncopal subjects during head-up tilt may signal the beginnings of cardiovascular decompensation associated with haemorrhage. We therefore tested the hypotheses that intense LBNP disrupts MSNA firing characteristics and leads to a dissociation between arterial pressure and sympathetic traffic prior to presyncope. In 17 healthy volunteers (12 males and 5 females), we recorded ECG, finger photoplethysmographic arterial pressure and MSNA. Subjects were exposed to 5 min LBNP stages until the onset of presyncope. The LBNP level eliciting presyncope was denoted as 100% tolerance, and then data were assessed relative to this normalised maximal tolerance by expressing LBNP levels as 80, 60, 40, 20 and 0% (baseline) of maximal tolerance. Data were analysed in both time and frequency domains, and cross-spectral analyses were performed to determine the coherence, transfer function and phase angle between diastolic arterial pressure (DAP) and MSNA. DAP-MSNA coherence increased progressively and significantly up to 80% maximal tolerance. Transfer functions were unchanged, but phase angle shifted from positive to negative with application of LBNP. Sympathetic bursts fused in 10 subjects during high levels of LBNP (burst fusing may reflect modulation of central mechanisms, an artefact arising from our use of a 0.1 s time constant for integrating filtered nerve activity, or a combination of both). On average, arterial pressures and MSNA decreased significantly the final 20 s before presyncope (n = 17), but of this group, MSNA increased in seven subjects. No linear relationship was observed between the magnitude of DAP and MSNA changes before presyncope (r = 0.12). We report three primary findings: (1) progressive LBNP (and presumed progressive arterial baroreceptor unloading) increases cross-spectral coherence between arterial pressure and MSNA, but sympathetic baroreflex control is reduced before presyncope; (2) withdrawal of MSNA is not a prerequisite for presyncope despite significant decreases of arterial pressure; and (3) reductions of venous return, probably induced by intense LBNP, disrupt MSNA firing characteristics that manifest as fused integrated bursts before the onset of presyncope. Although fusing of integrated sympathetic bursts may reflect a true physiological compensation to severe reductions of venous return, duplication of this finding utilizing shorter time constants for integration of the nerve signal is required.

Figure 1

Muscle sympathetic nerve activity is shown for one representative subject during progressive lower body negative pressure.

Figure 3. Muscle sympathetic activity and ECG tracings are shown for two different subjects

Subject A075 (top panels) demonstrated burst fusing, and subject A142 (bottom panels) did not. Heart rates (HR) were similar between the two subjects (upper right hand corner of the ECG panels).

Figure 2

Coupling (−60 mmHg) and then fusing (−90 mmHg) of muscle sympathetic nerve activity is shown for one representative subject during lower body negative pressure.

Figure 4

Example showing how individual bursts are detected in relation to preceding R-waves for single bursts (top panels) and fused bursts (bottom panels) of muscle sympathetic nerve activity.

Figure 6

Diastolic pressure (DAP)-to-muscle sympathetic nerve activity (MSNA) transfer gain, phase and coherence are shown for the entire subject cohort as a function of normalised levels of lower body negative pressure (LBNP); *significant deviation from baseline; **significant deviation from 40%.

Figure 5

Arterial pressure and muscle sympathetic time series are shown in the left panels; conversion of time series to the frequency domain are shown in the middle panels; cross spectral associations are shown in the right panels for one representative subject during −60 mmHg lower body negative pressure (subject experienced presyncope at −90 mmHg).

Figure 7. Arterial pressure (AP) and muscle sympathetic nerve activity (MSNA) is shown for three representative subjects 2 min before the onset of presyncope

The lowest arterial pressure (BP) recorded for each subject is shown in the upper right corner of the AP panel.

Figure 8. Changes of muscle sympathetic nerve activity (MSNA) are plotted as a function of changes of diastolic (DAP) and systolic (SAP) pressure

Changes were calculated by subtracting mean values recorded during the last 20 s before presyncope from mean values recorded during 40 s to 20 s before presyncope. Numbers of subjects deviating either above or below zero are separated by the horizontal (change in MSNA) and vertical (change in arterial pressure) dashed lines.