Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure.

RATIONALE: There is increasing evidence of increased ventilatory instability in patients with obstructive sleep apnea (OSA), but previous investigations have not studied whether the hypocapnic apneic threshold is altered in this group. OBJECTIVES: To compare the apneic threshold, CO2 reserve, and controller gain between subjects with and without OSA matched for age, sex, and body mass index. METHODS: Hypocapnia was induced via nasal mechanical ventilation for 3 minutes. Cessation of mechanical ventilation resulted in hypocapnic central hypopnea or apnea depending upon the magnitude of the hypocapnia. The apnea threshold (Pet(CO2)-AT) was defined as the measured Pet(CO2) at which the apnea closest to the last hypopnea occurred. The CO2 reserve was defined as the change in Pet(CO2) between eupneic Pet(CO2) and Pet(CO2)-AT. Controller gain was defined as the ratio of change in Ve between control and hypopnea or apnea to the DeltaPet(CO2). MEASUREMENTS AND MAIN RESULTS: Eleven pairs of subjects were studied. There was no difference in the Pet(CO2)-AT between the two groups. However, the CO2 reserve was smaller in the subjects with OSA (2.2 +/- 0.6 mm Hg) compared with the control subjects (4.5 +/- 1.4 mm Hg; P < 0.001). The controller gain was increased in the subjects with OSA (3.7 +/- 1.3 L/min/mm Hg) compared with the control subjects (1.6 +/- 0.5 L/min/mm Hg; P < 0.001). Controller gain decreased and CO2 reserve increased in seven subjects restudied after using continuous positive airway pressure for 1 month. CONCLUSIONS: Ventilatory instability is increased in subjects with OSA and is reversible with the use of continuous positive airway pressure.

Expiratory effort enhancement and peak expiratory flow in humans.

Peak expiratory flow (PEF) has previously been considered an effort-dependent, non flow-limited parameter that is constrained by the force-velocity relationship of the respiratory muscles. It has also been assumed that, if the muscles were able to augment the expiratory pressure, the PEF would increase. We tested the validity of this notion in normal volunteers who were able to enhance their expiratory pressure with maneuvers utilizing the stretch-shortening cycle (greater force when contractions were immediately preceded by eccentric contractions). Five healthy volunteers [35 (2) years] performed two successive maximal expiratory flow-volume maneuvers (MEFV) in rapid sequence. MEFV1 was a standard maneuver, whereas MEFV2 included a forceful inspiration to total lung capacity; a strategy designed to augment expiratory pressure via the stretch-shortening cycle. Neither maneuver included a post-inspiratory pause. We measured PEF, esophageal pressure (P(es)), and the electromyographic activity of the abdominal muscles. Compared to MEFV1, MEFV2 produced greater activation of the abdominal muscles during inspiration (eccentric contraction), greater peak expiratory P(es), greater rate of rise of P(es), shorter time to PEF, but similar PEF. Our findings directly demonstrate the inability of the augmented expiratory effort to increase PEF and thus support the notion that PEF is determined by a flow-limiting mechanism and not by the velocity of muscle shortening.

Treatment with leuprolide acetate decreases the threshold of the ventilatory response to carbon dioxide in healthy males.

This investigation was designed to determine if suppression of testosterone alters the ventilatory response to carbon dioxide in the presence of high and low levels of oxygen. Eleven healthy male subjects completed a series of rebreathing trials during wakefulness, before and after treatment with a long-acting gonadotropin-releasing hormone agonist. Five subjects also completed studies during non-rapid eye movement (NREM) sleep. During wakefulness, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (P(ET,CO2)) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen (140 Torr) gas mixture. During each trial P(ET,CO2) increased while oxygen was maintained at a constant level. The threshold of the ventilatory response to carbon dioxide was considered to be the point at which minute ventilation began to rise in a linear fashion as P(ET,CO2) increased. The slope of the ventilatory response above the threshold was used as a measure of sensitivity to carbon dioxide. During NREM sleep, hypocapnia was induced via nasal mechanical ventilation. Several trials were completed until the cessation of mechanical ventilation resulted in a central apnoea which demarcated the threshold of the ventilatory response to carbon dioxide. In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 +/- 0.77 versus 39.40 +/- 0.83 Torr; P = 0.01) and high (46.32 +/- 0.56 versus 44.78 +/- 0.83 Torr; P = 0.01) oxygen levels. An increase in sensitivity (4.82 +/- 0.61 versus 7.17 +/- 1.20 l min(-1) Torr(-1); P = 0.02) was also observed during rebreathing in the presence of high but not low oxygen levels. The increase in sensitivity was accompanied by an increase in carbon dioxide production. The findings observed during NREM sleep were similar to those observed during wakefulness, since the P(ET,CO2) that demarcated the threshold was decreased after leuprolide treatment (42.1 +/- 0.6 versus 39.6 +/- 0.6 Torr; P = 0.002). Additionally, the decrease in P(ET,CO2) required to induce an apnoea was greater after treatment with leuprolide (2.56 +/- 0.25 versus 4.06 +/- 0.29 Torr; P = 0.004). We conclude that suppression of testosterone decreases the threshold of the ventilatory response to carbon dioxide during both wakefulness and sleep.