Recruitment pattern of sympathetic neurons during breath-holding at different lung volumes in apnea divers and controls
Introduction
Trained breath-hold divers (BHD) are capable of enduring extremely long periods of apnea. The current world record for static apnea for males is 11 min 35 s (AIDA international). After such a maximal apnea, alveolar oxygen partial pressure can be as low as 20–30 mm Hg with arterial oxygen saturation around 50% (Lindholm and Lundgren, 2006, Overgaard et al., 2006). Such periods of oxygen desaturation are also correlated with increases in muscle sympathetic nerve activity (MSNA) (Heusser et al., 2009). Further, Heusser et al. (2009) showed that, when compared to baseline, the overall increase in MSNA during breath-holding in trained BHD is > 20-fold, a level that is ~ 5 times higher than observed in untrained control subjects. Under such conditions, increases in the action potential (AP) firing frequency and/or the recruitment of postganglionic sympathetic neurons may be necessary in order to enable such a large augmentation in MSNA. However, sympathetic neural firing patterns and strategies of activation of sympathetic nervous system, to date, are not clarified completely.
To address the issue of postganglionic recruitment strategies previous studies examined single-unit recordings and showed that sympathetic neurons, when active, fire predominantly once with a given burst of activity (~ 70% of occurrences) (Macefield et al., 1994, Macefield and Wallin, 1999) with the probability of multiple firings of the same neuron within a burst increasing during voluntary apnea (Macefield and Wallin, 1999) and with certain pathologies (Elam et al., 2003). A different but complementary approach is needed if one aims to determine discharge patterns of the multi-unit MSNA neurogram and to see if new action potentials appear in the recording.
To expand on this single neuron approach, and examine how the multi-unit signal changes with reflex activation, we have used a new spike detection algorithm that uses the continuous wavelet transform approach that enables determination of the number of sympathetic APs contributing to the multiunit MSNA (Salmanpour et al., 2010). Steinback et al. (2010b) recently applied this technique to analyze sympathetic activity in BHD during a prolonged, maximal end-inspiratory breath-hold. This earlier study suggested that large sympathetic neurons, which generate larger APs and faster conduction velocities, may be silent at rest but may be recruited during chemoreceptor-induced increases in sympathetic drive at the end of maximal end-inspiratory apneas.
Breath-holds starting at different lung volumes elicit increase in sympathetic neural traffic through different mechanisms. The sympathetic response to a breath-hold starting at functional residual capacity (FRC) of the lungs appears to be controlled principally by arterial oxygen desaturation and increasing levels of blood CO2 (Somers et al., 1989), representing a dominant influence of chemoreflex stress. However, the increase in sympathetic nervous traffic during total lung capacity (TLC) breath-hold is driven by diverse stimuli present at different phases of the TLC breath-hold, causing a biphasic response in MSNA. During the initial 30 s of TLC breath-hold the SNA response resembles that observed during a Valsalva maneuver (Heusser et al., 2009). This neural response likely is due to the high intrathoracic pressure that, in turn, reduces venous return and cardiac output eliciting unloading of low and high-pressure baroreceptors (Ferrigno et al., 1986, Macefield and Wallin, 1995). After the initial phase of the TLC breath-hold, blood pressure stabilizes but MSNA continues to increase linearly towards the end of the breath-hold. The underlying mechanisms for the increase in MSNA during the latter phase of the breath-hold must include an increase of chemoreflex stress (Somers et al., 1989, Morgan et al., 1993, Heusser et al., 2009) and the lack of ventilatory MSNA inhibition (Somers et al., 1989).
The purpose of the present study was to test the hypothesis that the sympathetic response to either FRC or TLC apneas would be greater in BHD compared with controls due simply to the ability of the divers to sustain a greater duration of breath-hold and the consequent magnitude of chemoreflex stress, rather than a training-induced difference in sympathetic AP recruitment.
Section snippets
Subjects
For the purposes of this study we recruited 19 healthy, male subjects (nine elite breath-hold divers and 10 matched control subjects). After receiving verbal and written instructions outlining the experimental procedures, and having providing informed written consent, subjects underwent the protocol. In fourteen (6 control subjects and 8 breath-hold divers), good quality MSNA recordings were obtained. Anthropometrics and diving history are presented in Table 1.
All participants were non-smokers
Results
Controls performed FRC breath-holds which lasted 27.7 (22.2–33.2) s, significantly shorter than the FRC breath-holds in the BHD group (60.4 (34.3–86.5) s (P = 0.006)). Breath-hold duration at TLC lasted on average 156.5 (106.5–206.5) s in the control group and 214.0 (172.6–255.4) s in the BHD group (P = 0.07).
Discussion
The main finding of our study is that the levels and recruitment patterns of sympathetic neuron activity during FRC (isolated chemoreflex stimulation) and TLC breath-holds (combined activation of baroreflex and chemoreflex) are similar in BHD vs. control subjects if the breath-hold is similar in duration. In other words, if control subjects are brought to the comparable level of chemoreflex stress as BHD by performing a prolonged breath-hold of at least several minutes (3 min in current study),
Conclusion
In summary, our study has shown that prolonged breath-holds result in a considerable increase in MSNA which is reached both by an increase in burst incidence, (i.e. increased firing frequency of sympathetic neurons), by the recruitment of previously silent, larger (faster conducting) neurons, and possibly by repeated firing within the same burst. However, different patterns of activation of postganglionic sympathetic neurons were observed depending on whether the provocation was a TLC or FRC
Acknowledgments
The authors would like to thank Ivana Banic, Dr. Dubravka Glucina, Dr. Jasenka Kraljevic, and Dr. Petra Zubin for their assistance in data collection. This study was funded by the Croatian Ministry of Science, Education and Sports grant no. 216-2160133-0130 to Z Dujic, and by the Natural Sciences and Engineering Research Council of Canada (NSERC) to JK Shoemaker. CD Steinback was supported by a NSERC Alexander Graham Bell Canadian Graduate Scholarship and a NSERC Michael Smith Foreign Study
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