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. 2023 Feb 8:14:1101408.
doi: 10.3389/fphys.2023.1101408. eCollection 2023.

The superior cervical ganglion is involved in chronic chemoreflex sensitization during recovery from acute lung injury

Kajal Kamra  1   2 , Nikolay Karpuk  2 , Irving H Zucker  1 , Harold D Schultz  1 , Han-Jun Wang  1   2
Affiliations

The superior cervical ganglion is involved in chronic chemoreflex sensitization during recovery from acute lung injury

Kajal Kamra et al. Front Physiol. .

Abstract

Introduction: Acute lung injury (ALI) initiates an inflammatory cascade that impairs gas exchange, induces hypoxemia, and causes an increase in respiratory rate (fR). This stimulates the carotid body (CB) chemoreflex, a fundamental protective reflex that maintains oxygen homeostasis. Our previous study indicated that the chemoreflex is sensitized during the recovery from ALI. The superior cervical ganglion (SCG) is known to innervate the CB, and its electrical stimulation has been shown to significantly sensitize the chemoreflex in hypertensive and normotensive rats. We hypothesized that the SCG is involved in the chemoreflex sensitization post-ALI. Methods: We performed a bilateral SCG ganglionectomy (SCGx) or sham-SCGx (Sx) in male Sprague Dawley rats 2 weeks before inducing ALI (Week -2 i.e., W-2). ALI was induced using a single intra-tracheal instillation of bleomycin (bleo) (day 1). Resting-fR, Vt (Tidal Volume), and V̇ E (Minute Ventilation) were measured. The chemoreflex response to hypoxia (10% O2, 0% CO2) and normoxic-hypercapnia (21% O2, 5% CO2) were measured before surgery on W (-3), before bleo administration on W0 and on W4 post-bleo using whole-body plethysmography (WBP). Results: SCGx did not affect resting fR, Vt and V̇E as well as the chemoreflex responses to hypoxia and normoxic hypercapnia in either group prior to bleo. There was no significant difference in ALI-induced increase in resting fR between Sx and SCGx rats at W1 post-bleo. At W4 post-bleo, there were no significant differences in resting fR, Vt, and V̇E between Sx and SCGx rats. Consistent with our previous study, we observed a sensitized chemoreflex (delta fR) in response to hypoxia and normoxic hypercapnia in Sx rats at W4 post-bleo. However, at the same time, compared to Sx rats, the chemoreflex sensitivity was significantly less in SCGx rats in response to either hypoxia or normoxic hypercapnia. Discussion: These data suggest that SCG is involved in the chemoreflex sensitization during ALI recovery. Further understanding of the underlying mechanism will provide important information for the long-term goal of developing novel targeted therapeutic approaches to pulmonary diseases to improve clinical outcomes.

Keywords: acute respiratory distress syndrome; bleomycin; carotid body; chemoreceptors; glomus cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Timeline showing experimental design.
FIGURE 2
FIGURE 2
Representative recordings of resting breathing at normoxia (left) and 10% hypoxia (right) obtained in one rat per experimental group: (A–C) Sx (in blue) at W0, W1 and W4, respectively; (D–F) SCGx (in green) at W0, W1 and W4, respectively.
FIGURE 3
FIGURE 3
Effect of Sx (n = 10) and SCGx (n = 8) on both resting ventilatory parameters (A–C) and chemoreflex activation in response to either 10% hypoxia (D–F) or to 5% normoxic-hypercapnia (G–I) in rats prior to bleo-treatment. Two-way ANOVA was applied using Bonferroni multiple comparisons, Values are mean ± SD; (A) Respiratory rate (fR); (B) Tidal volume (Vt); (C) Minute ventilation (V̇ E). (D–F) changes in ventilatory parameters including fR, Vt and V`˙ E in response to 10% hypoxia in rats prior to bleo-treatment. (G–I) changes in ventilatory parameters including fR, Vt and V̇ E in response to 5% normoxic-hypercapnia in rats prior to bleo-treatment.
FIGURE 4
FIGURE 4
Effect of Sx (n = 10) and SCGx (n = 8) on resting ventilatory parameters-(A) Respiratory rate (fR); (B) Tidal volume (Vt); (C) Minute ventilation (V̇ E) and, (D) Post-sigh Apneas and (E) Apnea-hypopnea Index (AHI) in bleo rats at W1 and W4 post-bleo. Two-way ANOVA was applied using Bonferroni multiple comparisons, Values are mean ± SD.
FIGURE 5
FIGURE 5
Effect of SCGx (n = 8) on sensitized chemoreflex activity on ventilatory parameters in response to hypoxia at W4 post-bleo. Two-way ANOVA was applied using Bonferroni multiple comparisons, Values are mean ± SD; (A) Respiratory rate (fR); (B) Delta fR; (C) Tidal volume (Vt); (D) Delta Vt; (E) Minute ventilation (V̇ E); (F) Delta V̇ E.
FIGURE 6
FIGURE 6
Effect of SCGx (n = 8) on sensitized chemoreflex activity on ventilatory parameters in response to normoxic-hypercapnia at W4 post-bleo. Two-way ANOVA was applied using Bonferroni multiple comparison, Values are mean ± SD; (A) Respiratory rate (fR); (B) Delta fR; (C) Tidal volume (Vt); (D) Delta Vt; (E) Minute ventilation (V̇E); (F) Delta V̇ E.
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