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. Abbreviations AP, arteri...

The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia

“…MCA diameter does not change with mild sympathetic activation induced by LBNP up to Ϫ40 mmHg (39), which may be comparable to our LT group, but not the HT group, as they reached levels of LBNP Ն 70 mmHg. During greater levels of LBNP, there is increased sympathetic nerve activity in the periphery (8), but it is unknown whether cerebral sympathetic activity also increases, which could constrict the cerebral vessels. If this did occur, however, CBF would be further decreased relative to the observed reduction in velocity (i.e., we would be underesti-mating the reduction in flow).…”

“…Despite similar reductions in MCAv in both groups, however, there was an immediate and progressive decrease in ScO 2 in the LT group only from Ϫ15 mmHg LBNP (P ϭ 0.004, Cohen's dϭ1. 8), but no change in ScO 2 for the HT group at any level of LBNP up to Ϫ60 mmHg; ScO 2 only began to fall below baseline from Ϫ75 mmHg LBNP in HT subjects (P Ͻ 0.001, Data are expressed as means Ϯ SD for age, height, weight, and means Ϯ SE for all other data. HT, high tolerance; LT, low tolerance; LBNP, lower body negative pressure; HR, heart rate; MAP, mean arterial pressure.…”

Contribution of left atrial volume and function in neurocardiogenic syncope

“…Vaddadi et al (8) demonstrated that efferent sympathetic activity was maintained during vasovagal syncope episodes, and they speculated that activation of vasodiIator mechanisms may be responsible for vasovagal syncope. In addition, Cooke et al (9) showed that withdrawal of muscle sympathetic activity is not mandatory for presyncope. Some studies have shown that without decrease in peripheral vascular resistance, decrease in cardiac output alone can cause presyncope (1,10).…”

The pathophysiologic mechanisms associated with hypotensive susceptibility

“…Recently, the above hypothesis has been challenged by studies showing that sympathetic withdrawal was not a pre-requisite for syncope [8,14,38]. Indeed, more than 2 decades ago, VVS was reported in heart transplant recipients and more recently several investigators made the observation that decreases in cardiac output contributed to the hypotension independent of reflex-mediated changes [14,20,39].…”