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Sleep Research Laboratory, Medical Service, John D. Dingell Veterans Affairs Medical Center, and Division of Pulmonary/Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201
Long-term facilitation (LTF) is a
prolonged increase in ventilatory motor output after episodic
peripheral chemoreceptor stimulation. We have previously shown that LTF
is activated during sleep following repetitive hypoxia in snorers
(Babcock MA and Badr MS. Sleep 21: 709-716,
1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of
eliminating inspiratory flow limitation by nasal CPAP on LTF. We
studied 25 normal subjects during stable non-rapid eye movement sleep.
We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O2 fraction = 8%; 3 min) followed by 5 min of room
air. Measurements were obtained during control and at 20 min of
recovery (R20). During the episodic hypoxia study,
inspiratory minute ventilation (
I) increased from
6.7 ± 1.9 l/min during the control period to 8.2 ± 2.7 l/min at R20 (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory
flow limitation during control was the only independent determinant of
the presence of LTF (P = 0.005). Six subjects
were restudied by using nasal continuous positive airway pressure to
ascertain the effect of eliminating inspiratory flow limitation on LTF.
I during the recovery period was 97 ± 10%
(P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increased
I in the recovery period, indicative of development
of LTF; 2) inspiratory flow limitation is the only
independent determinant of posthypoxic LTF in sleeping human;
3) elimination of inspiratory flow limitation abolished the
ventilatory manifestations of LTF; and 4) we propose that
increased I in the recovery period was a result of
preferential recruitment of upper airway dilators by repetitive hypoxia.
episodic hypoxia; ventilatory control; plasticity; non-rapid eye movement sleep
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