Laryngeal constriction during hypoxic gasping and its role in improving autoresuscitation in two mouse strains

Abstract

Laryngeal closure following hypoxic gasps has been documented, but its efficacy in improving autoresuscitation capacity is unknown. We studied SWR/J mice who normally cannot autoresuscitate and the C57/BLJ strain who can. We evaluated the effects of elevated end-inspiratory lung volume immediately following a gasp. We compared upper airway-intact mice with tracheostomized mice in which the vocal cords are bypassed. We used the techniques of repeated autoresuscitate trials to test autoresuscitation capability. Both SWR/J and C57/BLJ mice could maintain elevated lung volume immediately after a gasp (breath holding). Such breath holding increased autoresuscitation ability in C57/BLJ mice but did not in SWR/J mice. In SWR/J mice, the duration of the breath holds was less than that in the C57/BLJ mice. These findings indicate that gasp-associated breath holding improves autoresuscitation capability during repeated autoresuscitation trials. Also, they show that SWR/J mice have a deficiency in central nervous system mechanisms regulating glottic closure during hypoxic gasping.

Fig. 1.

A: tracing of respiration in a C57/BLJ mouse during an autoresuscitation (AR) trial. Gasps (G) 1, 6, 7, and 8 were counted in our protocol. Those during seizures, G2-5, were not. Note that some degree of end-inspiratory breath holding is present during hypoxic hyperpnea. After a 1.5-s time lapse between breaths, N₂/CO₂ is discontinued and is replaced by air. Our protocol was giving air after 1 s, but there was some degree of variability in attempting to reach this precise target. Note the prolonged breath hold after the first gasp and its absence in gasps during hypoxic seizures. The final gasps before recovery (G10 and 11) have decreased peak inspiratory volume, possibly due to decreased neural output from the medulary center(s) that regulates gasping. B: tracing of respiration in a tracheostomized C57/BLJ mouse during an AR trial. Note the absence of breath holding associated with gasps. The first 4 gasps were considered in our protocol. Insp, inspiratory; Exp, expiratory.

Fig. 2.

Duration of gasp-associated breath holding in upper airway-intact vs. tracheostomized SWR/J and C57/BLJ mice. Duration of expiratory time is longer in upper airway-intact mice than in tracheostomized mice. Note that expiratory time prolongation is greater in C57/BLJ mice compared with SWR/J mice.

Fig. 3.

Progressive changes in breath holding duration (expiratory time) in SWR/J and C57/BLJ mice with repeated hypoxic exposures. Since the C57/BLJ mice underwent an increased number of trials, their overall exposure to hypoxia was increased compared with that of SWR/J mice. Data for the initial 4 trials, the middle AR trial, and the terminal 4 trials are shown. Note the increased duration of gasp-associated breath holding in C57/BLJ mice as opposed to SWR/J mice. Also note the increasing duration of breath holds with the increasing number of trials.

Fig. 4.

Number (N) of successful AR trials in upper airway-intact and tracheostomized SWR/J and C57/BLJ mice. Note that both tracheostomized and airway-intact SWR mice had reduced trials compared with C57/BLJ mice. Also note that the upper airway-intact C57/BLJ mice had more successful trials than tracheostomized mice. However, this was not the case in SWR/J mice. NS, nonsignificant.