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1 Physiology, Wayne State University, Detroit, Michigan, United States; Research and Development, John D. Dingell VA Medical Center, Detroit, Michigan, United States
2 Research and Development, John D. Dingell VA Medical Center, Detroit, Michigan, United States
3 Internal Medicine, Wayne State University, Detroit, Michigan, United States; Physiology, Wayne State University, Detroit, Michigan, United States; Biomedical Engineering, Wayne State University, Detroit, Michigan, United States
4 Internal Medicine, Wayne State University, Detroit, Michigan, United States; Physiology, Wayne State University, Detroit, Michigan, United States; Research and Development, John D. Dingell VA Medical Center, Detroit, Michigan, United States
* To whom correspondence should be addressed. E-mail: jmateika{at}med.wayne.edu.
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 following exposure to eight 4-minute 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.
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