Long-term facilitation of ventilation and genioglossus muscle activity is evident in the presence of elevated levels of carbon dioxide in awake humans

Abstract

We hypothesized that long-term facilitation (LTF) of minute ventilation and peak genioglossus muscle activity manifests itself in awake healthy humans when carbon dioxide is sustained at elevated levels. Eleven subjects completed two trials. During trial 1, baseline carbon dioxide levels were maintained during and after exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven subjects were exposed to sustained elevated levels of carbon dioxide in the absence of episodic hypoxia, which served as a control experiment. Minute ventilation was measured during trial 1, trial 2, and the control experiment. Peak genioglossus muscle activity was measured during trial 2. Minute ventilation during the recovery period of trial 1 was similar to baseline (9.3 +/- 0.5 vs. 9.2 +/- 0.7 l/min). Likewise, minute ventilation remained unchanged during the control experiment (beginning vs. end of control experiment, 14.4 +/- 1.7 vs. 14.7 +/- 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle activity during the recovery period of trial 2 was greater than baseline (minute ventilation: 28.4 +/- 1.7 vs. 19.6 +/- 1.0 l/min, P < 0.001; peak genioglossus activity: 1.6 +/- 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and peak genioglossus muscle activity and that LTF is only evident in awake humans in the presence of sustained elevated levels of carbon dioxide.

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

“…The occurrence of GG LTF in sleeping humans is in contrast to studies during wakefulness that have shown no evidence of GG LTF (McEvoy et al 1996, Jordan et al 2002, unless episodic hypoxia was accompanied by hypercapnia (Harris et al 2006). The discrepancy between wakefulness and NREM sleep vis-à-vis GG LTF could be attributed to higher upper airway resistance during sleep, augmenting negative supraglottic pressure and the magnitude of GG activation.…”

“…Experimental conditions also influence the development of LTF. An example is the occurrence of LTF following episodic hypoxia in awake human subjects, only in the presence of concomitant hypercapnia (Harris et al 2006). Finally, LTF may manifest differently across different motor nuclei, manifesting in the phrenic motorneuron (Fuller et al 2000) or hypoglossal motorneuron (Bach and Mitchell, 1996).…”

Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia

“…This, along with the potential stress associated with contention, may contribute to prevent ventilatory LTF. Finally, ventilatory LTF expression in adult rats is larger under iso-and hypercapnic conditions (18,45). Because our experiments were done under poikilocapnic hypoxia, this may further limit LTF.…”

Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation

“…IH protocol (eight 4-min periods of hypoxia (inspiratory oxygen fraction (FIO 2 ) 8%), separated by 5 min of normoxia (FIO 2 21%)) describe an increase in both tidal volume and breathing frequency [37,38]. Thus, findings regarding the ventilatory pattern of IH-induced LTF is equivocal, and probably the result of varying IH protocols.…”