Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

Abstract

This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRC_Apnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRC_Apnea) hemoglobin saturation (HbSat) levels (RBR_Matched) or more severe levels (RBR_End). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBR_ALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBR_Matched was associated with reduced AP frequency and APs per burst compared with FRC_Apnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRC_Apnea (+10 ± 2; P < 0.001) but not during RBR_Matched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBR_End (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBR_End was associated with a restrained increase in the APs per burst (FRC_Apnea: +18 ± 7; RBR_End: +11 ± 5) and total AP clusters (FRC_Apnea: +10 ± 2; RBR_End: +6 ± 4) (both P < 0.01). During FRC-RBR_ALT, all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress.NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.

Keywords: action potential; chemoreflex; muscle sympathetic nerve activity.

Fig. 1.

Representative recordings of the integrated muscle sympathetic nerve activity (MSNA) neurogram and detected action potentials (APs) (and associated chemoreflex stimuli) from one individual during the functional residual capacity (FRC) apnea and rebreathing (RBR) protocols. Po₂, partial pressure of oxygen; Pco₂, partial pressure of carbon dioxide; HbSat, hemoglobin saturation. Highlighted (i.e., boxed) areas represent portions of the maneuver used for analysis.

Fig. 2.

Sympathetic action potential (AP) recruitment during baseline (BSL), initial rebreathe (RBR), and maneuver (MAN) periods of the FRC_Apnea and RBR_Matched protocols. *P < 0.05, significantly different from BSL. †P < 0.01, significantly different from RBR_Matched.

Fig. 3.

Sympathetic action potential (AP) recruitment during baseline (BSL), initial rebreathe (RBR), and maneuver (MAN) periods of the FRC_Apnea and RBR_End protocols. *P < 0.05, significantly different from BSL. †P < 0.01, significantly different from RBR_End.

Fig. 4.

Representative recordings of the integrated muscle sympathetic nerve activity (MSNA) neurogram and detected action potentials (APs) (and associated chemoreflex stimuli) from one individual during the alternating functional residual capacity (FRC) apnea and rebreathe (RBR) protocol (FRC-RBR_ALT). Po₂, partial pressure of oxygen; Pco₂, partial pressure of carbon dioxide; HbSat, hemoglobin saturation. Boxed area represents the portion of the maneuver used for analysis (see insets).

Fig. 5.

Sympathetic action potential (AP) recruitment during baseline (BSL) and alternating periods of apnea at functional residual capacity (FRC) and rebreathe (RBR). HbSat, hemoglobin saturation. *P < 0.001, significantly different from BSL. †P < 0.001, significantly different from corresponding RBR.