The purpose of this study was to determine the influence of tidal volume, breathing pattern, and beginning lung volume on the modulation of efferent, muscle sympathetic nerve activity (MSNA) in humans. In seven supine, healthy subjects, we measured MSNA (microneurography of the right peroneal nerve) and beat to beat arterial blood pressure during 1) low-frequency breathing (fb = 12 breaths/min) at tidal volumes (VT) of 30% (control), 50%, and 70% of inspiratory capacity and with inspiratory time-to-total breath time ratios (TI/TTOT) of 0.3-0.5 (control), less than 0.3, and greater than 0.5; and 2) simulated exercise hyperpnea (fb = 40 breaths/min; VT = 60-70% inspiratory capacity; minute ventilation, approximately 90 1). To optimize our ability to discern modulatory effects, breathing was performed during three conditions of heightened MSNA: nonhypotensive (less than 20 mm Hg) lower-body negative pressure, isometric handgrip exercise, and posthandgrip vascular occlusion (ischemia). PETCO2 was maintained at normal levels by adjusting the FICO2. Within-breath modulation of MSNA was observed during control tidal breathing with approximately 65% of the burst frequency occurring during the expiratory phase. Deep, low-frequency breathing potentiated this modulatory influence (p less than 0.05 versus control) and produced near-complete sympathoinhibition from onset-mid inspiration to early-mid expiration. Increasing (slow inspiration) and decreasing (fast inspiration) TI/TTOT shifted the onset of sympathoinhibition occurring later (greater change in volume) and earlier (less change in volume) during inspiration, respectively. In two subjects who performed deep breathing from an elevated beginning lung volume, the sympathoinhibition was observed earlier in the inspiratory period and with less change in volume compared with control. These within-breath modulatory effects did not appear to be due solely to changes in arterial pressure. Sustained low- or high ("exerciselike")-frequency deep breathing did not alter total minute MSNA compared with control breathing. These results demonstrate that the depth and pattern of breathing, and possibly the starting lung volume, exert marked influences on the within-breath modulation of MSNA in humans. Our findings also suggest that these modulatory effects may be mediated, at least in part, by pulmonary stretch reflexes.

SUMMARY1. Our aim was to determine the influence of the type of task, the absolute and relative difficulty of the task, and the perceived stress associated with performance of the task on sympathetic circulatory regulation during cognitive challenge in humans.2. Sympathetic nerve activity to skeletal muscle (MSNA) determined from peroneal microneurography, heart rate and arterial blood pressure were recorded continuously in twelve subjects during a modified Stroop colour word test (CWT) and mental arithmetic (MA), each performed over six levels of increasing absolute task difficulty. Performance (percentage correct) on each task was assessed and ratings of perceived stress obtained. Responses to CWT and MA were compared at similar levels of performance and perceived stress. 3. MSNA decreased at task onset, remained below baseline levels at low levels of difficulty which were not perceived as stressful, increased above baseline levels at higher levels of difficulty which were perceived as stressful, and increased further during recovery. Thus, the regulation of MSNA was stress dependent. At similar levels of stress perception there were no differences in MSNA between CWT and MA. Although performance declined as task difficulty increased, there was no particular 'threshold' level of performance associated with the stimulation of MSNA.4. Arterial pressure and heart rate were elevated above baseline levels throughout the mental tasks. Arterial pressure increased over the first 3-4 levels of each task and then plateaued whereas heart rate did not vary across increasing levels of task difficulty. Heart rate and arterial pressure responses to CWT were higher than those to MA.5. These data demonstrate that during cognitive challenge the stimulation of MSNA is governed primarily by perceived stress which is dependent, in part, on the absolute level of task difficulty. In contrast, neither performance nor the type of cognitive task appear to be important determinants of MSNA. Arterial pressure is influenced by the task and level of difficulty. Heart rate is independent of task difficulty but may be task dependent.

We determined the influences of breathing-induced changes in intrathoracic and intravascular pressures, central respiratory drive, and pulmonary vagal feedback on the within-breath variation in skeletal muscle sympathetic nerve activity (MSNA) in humans. MSNA (peroneal microneurography), arterial blood pressure (Finapres finger monitor), and tidal volume (VT) were recorded continuously in six normal subjects and four heart-lung transplant patients during: 1) spontaneous air breathing; 2) increased FiCO2; 3) voluntary augmentation of VT with and without inspiratory resistance; and 4) positive pressure, passive mechanical ventilation. During conditions 3 and 4, which were performed under isocapnic conditions with a high MSNA background (either high resting activity or nonhypotensive lower body suction), subjects breathed at control or elevated VT with normal or prolonged inspiratory time (TI); breathing frequency was 12 breaths per minute. During control breathing in normal subjects there was a distinct within-breath pattern of MSNA, with "701O of the activity occurring during low lung volumes (initial half of inspiration and latter half of expiration). This within-breath variation of MSNA was potentiated with increased VT breathing (>85% of activity occurring during low lung volumes; p

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