Modulation of the control of muscle sympathetic nerve activity during severe orthostatic stress

Abstract

We tested the hypothesis that arterial baroreflex (ABR)-mediated beat-to-beat control over muscle sympathetic nerve activity (MSNA) is progressively modulated as orthostatic stress increases in humans, but that this control becomes impaired just before the onset of orthostatic syncope. In 17 healthy subjects, the ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (control) and during progressive, stepwise increases in lower body negative pressure (LBNP) that were incremented by -10 mmHg every 5 min until presyncope (nine subjects) or -60 mmHg was reached. (1) The linear relationships between DAP and burst strength and between DAP and total MSNA were shifted progressively upward as LBNP increased until the level at which syncope occurred. The relationship between DAP and burst incidence, however, gradually shifted upward from control only to LBNP = -30 mmHg; there was no further upward shift at higher LBNPs. (2) Although the slope of the relationship between DAP and burst strength and between DAP and total MSNA remained constant at all LBNPs tested, except at the level where syncope occurred, the slope of the relationship between DAP and burst incidence was reduced at LBNPs of -40 mmHg and higher (versus control). (3) In syncopal subjects, the slopes of the relationships between DAP and burst incidence, burst strength, and total MSNA were all substantially reduced during the 1-2 min period prior to the onset of syncope. Taken together, these results suggest baroreflex control over MSNA is progressively modulated as orthostatic stress increases, so that its sensitivity is substantially reduced during the period immediately preceding the severe hypotension associated with orthostatic syncope.

Figure 1. Raw recordings of arterial blood pressure and MSNA in the control situation and at LBNPs of −50 mmHg and −60 mmHg in a subject who experienced symptoms of presyncope at −60 mmHg

At LBNP = −60 mmHg, note the rapid decline in blood pressure and concomitant reduction in MSNA that occurred before the onset of syncope (the last part of the trace). In this subject, calculation of basal data (HR, blood pressure and MSNA) and analysis of ABR control over MSNA for LBNP = −60 mmHg were performed using the data obtained during the period between the dashed lines, when blood pressure and MSNA were largely stable.

Figure 2. Linear relationships between DAP and burst incidence (A and B), burst strength (C and D) and total MSNA (E and F) in the control situation and at LBNPs of −30 mmHg and −60 mmHg in a non-syncopal subject (A, C and E) and in a syncopal subject who experienced syncope at LBNP = −60 mmHg (B, D and F)

PPo, prevailing point.

Figure 3. The group averaged values of the slopes of the linear regression lines relating DAP and burst incidence (A), burst strength (B) and total MSNA (C) in the syncopal (n = 9 subjects) and non-syncopal (n = 3 subjects) subjects during the control situation and the three highest LBNP levels

*P < 0.05 versus control. †P < 0.05 versus the 2nd LBNP level.