Effect of varying chemoreflex stress on sympathetic neural recruitment strategies during apnea

Abstract

We sought to examine the effect of varying chemoreflex stress on sympathetic neural recruitment strategies during end-expiratory apnea. We hypothesized that increases in the firing frequency and probability of low-threshold axons at the asphyxic "break point" would be exaggerated during hypoxia and attenuated during hyperoxia. Multiunit muscle sympathetic nervous system activity (MSNA) (peroneal nerve microneurography) was measured in 10 healthy male subjects (31 ± 2 yr, 25 ± 1 kg/m²). Individuals completed maximal voluntary end-expiratory apnea under normoxic, hypoxic (inspired O₂ fraction: 0.17 ± 0.01), and hyperoxic (inspired O₂ fraction: 0.92 ± 0.03) conditions. Action potential (AP) patterns were examined from the filtered raw signal with wavelet-based methodology. Multiunit MSNA was increased (P ≤ 0.05) during normoxic apnea, because of an increase in the frequency and incidence of AP spikes (243 ± 75 to 519 ± 134 APs/min, P = 0.048; 412 ± 133 to 733 ± 185 APs/100 heartbeats, P = 0.02). Multiunit MSNA increased from baseline (P < 0.01) during hypoxic apnea, which was due to an increase in the frequency and incidence of APs (192 ± 59 to 952 ± 266 APs/min, P < 0.01; 326 ± 89 to 1,212 ± 327 APs/100 heartbeats, P < 0.01). Hypoxic apnea also resulted in an increase in the probability of a particular AP cluster firing more than once per burst (P < 0.01). Hyperoxia attenuated any increase in MSNA with apnea, such that no changes in multiunit MSNA or frequency or incidence of AP spikes were observed (P > 0.05). We conclude that increases in frequency and incidence of APs during apnea are potentiated during hypoxia and suppressed when individuals are hyperoxic, highlighting the important impact of chemoreflex stress in AP discharge patterns. The results may have implications for neural control of the circulation in recreational activities and/or clinical conditions prone to apnea.NEW & NOTEWORTHY Our results demonstrate that, compared with normoxic end-expiratory apnea, hypoxic apnea increases the frequency and incidence of action potential spikes as well as the probability of multiple firing. We further show that this response is suppressed when individuals are hyperoxic. These data highlight the potentially important role of chemoreflex stress in neural firing and recruitment and may have implications for neural control of the circulation in recreational and/or clinical conditions prone to apnea.

Keywords: breath hold; carotid body; hyperoxia; hypoxia; microneurography.

Fig. 1.

Schematic representation of action potential (AP) detection and classification. MSNA, muscle sympathetic nerve activity. Figure adapted from Badrov et al. (2015) with permission.

Fig. 2.

Representative data during normoxic apnea. Representative recording of heart rate, mean blood pressure (MBP), muscle sympathetic nerve activity (MSNA) neurogram, and detected action potentials (APs) from 1 individual (male, 26 yr old) during quiet normoxic rest (baseline) and end-expiratory apnea.

Fig. 3.

Sympathetic responses to normoxic apnea. Data are reported as means ± SE for n = 10 subjects. *P < 0.05 vs. baseline. Data were analyzed by using a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, apnea) and the interaction of cluster size and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated muscle sympathetic nerve activity (MSNA) burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst. C: probability of multiple clusters per integrated MSNA burst.

Fig. 4.

Sympathetic responses to hypoxic apnea. Data are reported as means ± SE for n = 7 subjects. *P < 0.05 vs. baseline; †P < 0.05 vs. hypoxia. Data were analyzed by using a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, hypoxia, apnea) and the interaction of cluster and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated muscle sympathetic nerve activity (MSNA) burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst. C: probability of multiple clusters per integrated MSNA burst.

Fig. 5.

Sympathetic responses to hyperoxic apnea. Data are reported as means ± SE for n = 9 subjects. Data were analyzed by using a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, hyperoxia, apnea) and the interaction of cluster and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated muscle sympathetic nerve activity (MSNA) burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst. C: probability of multiple clusters per integrated MSNA burst.