Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats

Abstract

1. Intermittent hypoxia elicits long-term facilitation (LTF) of phrenic motor output in anaesthetized rats. We tested the hypothesis that an equal cumulative duration of continuous hypoxia would not elicit phrenic LTF. 2. Integrated phrenic nerve activity was recorded in urethane-anaesthetized, vagotomized, paralysed and ventilated rats exposed to: (1) 3 X 3 min hypoxic episodes (inspired O2 fraction (FI, O2) = 0.11) separated by 5 min hyperoxia (FI,O2 = 0.5; n = 6), (2) 9 min continuous hypoxia (n = 6), or (3) 20 min continuous hypoxia (n = 7). Isocapnia was maintained throughout the protocol. 3. Consistent with previous studies, phrenic amplitude was significantly elevated for at least 1 h following intermittent hypoxia (78 +/- 15% 60 min post-hypoxia; P < 0.05) with an associated increase in burst frequency (11 +/- 2.1 bursts min-1; P < 0.05). In contrast, 9 or 20 min continuous hypoxia did not elicit LTF of either phrenic amplitude (4.7 +/- 5.1 and 10.1 +/- 10.2% 60 min post-hypoxia, respectively; P > 0.05) or frequency (4.6 +/- 1.3 and 5.1 +/- 2 bursts min-1 60 min post-hypoxia, respectively; P > 0.05). 4. The results indicate that hypoxia-induced long-term facilitation of phrenic motor output is sensitive to the pattern of hypoxic exposure in anaesthetized rats.

Figure 1. Integrated phrenic discharge in one rat exposed to episodic hypoxia and one rat exposed to 20 min continuous hypoxia

Integrated phrenic discharge during baseline, hypoxia, and 15, 30 and 60 min post-hypoxia. Only episodic hypoxia elicits LTF.

Figure 2. Changes in integrated phrenic and hypoglossal amplitude following episodic and continuous hypoxia

Mean integrated phrenic amplitude (±s.e.m.) at 15, 30 and 60 min following episodic (▪), and 9 min (•) and 20 min (▴) continuous hypoxia expressed as a percentage increase from pre-stimulation (baseline) levels. Episodic hypoxia elicited significant phrenic LTF at all time points. In contrast, 9 and 20 min continuous hypoxia did not elicit phrenic LTF. Neither episodic nor continuous hypoxia elicited significant hypoglossal LTF. *Significantly different from pre-stimulus baseline (P < 0.05); significantly different from 3 x 3 min episodic hypoxia.

Figure 3. Long-term facilitation of phrenic burst frequency following episodic, but not continuous hypoxia

Mean change in phrenic frequency from baseline (±s.e.m.) at 15, 30 and 60 min following episodic (▪) and 9 min (•) and 20 min (▴) continuous hypoxia. Episodic hypoxia elicited significant LTF of burst frequency at all time points. No LTF was observed following 9 or 20 min continuous hypoxia. *Significantly different from pre-stimulus baseline (P < 0.05); significantly different from 3 x 3 min episodic hypoxia (P < 0.05).