Inhibition of augmented muscle vasoconstrictor drive following asphyxic apnoea in awake human subjects is not affected by relief of chemical drive
Authors: Seitz Michael J. , Brown Rachael , Macefield Vaughan G. 
Published: August 2012

New findings

What is the central question of this study?

Breath holding to the asphyxic break point causes a progressive increase in muscle sympathetic nerve activity, which is then immediately inhibited on the resumption of breathing, presumably due to relief of the elevated chemical drive. The purpose of this study was to determine whether lung inflation per se, rather than the relief from hypoxia and hypercapnia, is responsible for the inhibition of muscle sympathetic nerve activity after an end‐expiratory apnoea.

What is the main finding and its importance?

We show in human subjects that the duration of this inhibition is the same whether the apnoea is terminated by taking a single breath of room air or of 100% N2 or 10% CO2+ 90% N2. Given that there will be no inhibition of chemoreceptors in the latter two conditions, we conclude that lung inflation itself causes the inhibition of muscle vasoconstrictor drive.

Progressive asphyxia, produced by a prolonged voluntary breath hold (end‐expiratory apnoea), evokes large bursts of muscle sympathetic nerve activity (MSNA). These bursts increase in amplitude until the asphyxic break point is reached, at which point the bursts are inhibited. We tested the hypothesis that lung inflation, rather than relief from hypoxia and hypercapnia, is responsible for the inhibition of MSNA. Multiunit MSNA was recorded from motor fascicles of the common peroneal nerve in 11 subjects. Following a period of quiet breathing, subjects were instructed to behave as follows: (i) to hold their breath in expiration for as long as they could (mean duration 32.3 ± 1.9 s); (ii) to take a single breath of room air, 100% N2 or 10% CO2 + 90% N2 at the asphyxic break point; (iii) to exhale and continue the apnoea until the next break point; and then (iv) to resume breathing. All subjects reported relief during inhalation of any gas, and could continue holding their breath for a further 30.7 ± 2.8 s with room air, 18.6 ± 1.7 s with N2 and 11.8 ± 1.8 s with 10% CO2 + 90% N2. Despite the exaggerated chemoreceptor drive in the latter two conditions (hence the significantly shorter latencies to the subsequent asphyxic break point), the inhibition still occurred; moreover, there was no significant difference in duration of the inhibition of MSNA following the single breath of room air (7.6 ± 0.7 s), N2 (6.2 ± 0.6 s) or 10% CO2 + 90% N2 (5.5 ± 0.4 s). Following the resumption of breathing, however, the duration of MSNA inhibition (11.0 ± 1.0 s) was significantly longer than that following a single breath. To investigate the involvement of chemoreceptors in the respiratory modulation of MSNA further, the same gases were used during an inspiratory‐capacity apnoea, which causes a brief inhibition of MSNA during the inflation phase and a sustained increase during the hold phase. The duration of the apnoea was shortest after a breath of 10% O2 + 90% N2, but the latency until the bursts resumed after the inspiratory breath hold were similar for all gases, which suggests that there is no chemoreceptor involvement during the sympathetic silence seen during the inflation phase of inspiratory‐capacity apnoeas. We conclude that neither peripheral nor central chemoreceptors are responsible for the inhibition of muscle vasoconstrictor drive following an end‐expiratory apnoea or an end‐inspiratory apnoea. Rather, we suggest that the inhibition is evoked by stretch receptors in the lungs and/or chest wall, which may also contribute to the longer inhibition associated with the hyperventilation following the subsequent resumption of rhythmic breathing.