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Volume 2 Supplement 1

Neural Control of Breathing

Chronic intermittent asphyxia impairs rat upper airway muscle responses to acute hypoxia and asphyxia

Sleep disordered breathing (SDB) is characterised by chronic intermittent asphyxia (CIA) due to repetitive apnoeas. We tested the hypothesis that CIA affects upper airway muscle activity and responses to acute hypoxia and asphyxia.

Wistar rats were placed in restrainers with their heads in hoods ventilated with air (controls, n = 6) or an air/N2/CO2 mixture intermittently (treated group, n = 6) for 8 h per day, 5 days per week for 5 weeks using timed solenoid valves as previously described [1]. In were added to the the treated group, every 30 s, N2 and CO2 to a minimum of 6–8% and airflow for 15 s reducing hood O2 increasing CO2 to a maximum of 12–14% followed by removal of the N2 and CO2 and recovery to room air values. After 5 weeks, animals were anaesthetised (chloralose and urethane, 100 and 1000 mg/kg respectively IP). Sternohyoid (SH) electromyogram (EMG) activity was measured breathing air, 7.5% O2 in N2 (hypoxia) and 7.5% O2 and 3% CO2 (asphyxia). EMG data were expressed as % of peak activity breathing 9% CO2 (% of reference).

Baseline SHEMG activity was significantly elevated in the treated group (28.4 ± 0.3% of reference in the controls vs. 48.5 ± 0.5% of reference in the treated group; means ± SEM, P < 0.05 ANOVA). CIA significantly reduced SHEMG responses to hypoxia and asphyxia. Thus, the increase in EMG activity from baseline values (ΔEMG) during the first minute of hypoxia was +46.2 ± 5.8% in control rats vs. +30.4 ± 6.1% in treated rats. Similarly, ΔEMG during the first minute of asphyxia was +66.3 ± 5.9% in control rats vs. +41.1 ± 11.1% in treated rats.

We suggest that the elevated upper airway muscle activity associated with SDB is due to CIA. We propose that a reduction in the response of upper airway dilator muscles to acute asphyxia following upper airway obstruction is likely to cause further asphyxic insult leading to a vicious feed-forward cycle. We further propose that CIA contributes to the pathophysiology of SDB and other conditions of intermittent asphyxia.

References

  1. 1.

    McGuire M, Bradford A: Chronic intermittent hypoxia raises haematocrit and causes right ventricular hypertrophy in the rat. Respir Physiol. 1999, 117: 53-58. 10.1016/S0034-5687(99)00047-X.

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Acknowledgement

This work was funded by the RCSI/Charitable Infirmary Charitable Trust.

Author information

Correspondence to T O'Hare.

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Keywords

  • Urethane
  • Sleep Disorder
  • Sleep Disorder Breathing
  • Solenoid Valve
  • Acute Hypoxia