There is as yet no convincing evidence that acetazolamide, a carbonic anhydrase inhibitor, is effective in obstructive sleep apnoea. A study was therefore designed to examine the effect of acetazolamide (250 mg/day) on sleep events and ventilatory control during wakefulness in nine patients with the sleep apnoea syndrome. In eight of the nine patients the apnoea index and the total duration ofapnoea were reduced by acetazolamide, and the mean (SEM) apnoea index of all patients changed from 25-0 (6 7) to 18 1 (5 8) episodes an hour. Furthermore, the total time of arterial oxygen desaturation (Sao2-more than 4% depression in Sao2 from the baseline sleeping level-divided by total sleep time was also significantly decreased and its mean (SEM) value improved from 24-1 (7 9) to 13-6 (4-8)% of total sleep time. Five

To determine the relationship between periodic breathing (PB) during sleep at high altitude and ventilatory chemosensitivities, we studied nine Japanese climbers who participated in the expedition to the Kunlun Mountains (7,167m) in China in 1986. At sea level, ventilatory response to hypoxia (HVR) by isocapnic progressive hypoxia test and to hypercapnia (HCVR) by Read's method were examined. At altitude 5,360 m, respiratory movements of the chest and abdominal wall, Saoz, ECG, and HR were monitored. Seven climbers manifested PB during sleep. There was a significant correlation between PB during sleep and HVR and HCVR (p <0.05). All the climbers showed severe desaturation during sleep. There was a significant negative correlation between degree of desaturation during sleep and HVR (p <0.05). A negative correlation was also detected between PB and the degree of desaturation during sleep. We concluded that ventilatory chemosensitivities play an important role in eliciting PB and that climbers with high HVR can maintain their arterial oxygenation during sleep, due to hyperventilation induced by PB, which is considered an advantageous adaptation for lowland sojourners.

The effects of acetazolamide, a potent carbonic anhydrase inhibitor, and ammonium chloride (NH4C1) on arterial blood gas tension, resting ventilation, and ventilatory responses to CO2 (HCVR) and hypoxia (HVR) were studied in healthy male subjects. Both drugs induced chronic metabolic acidosis with the reduction in plasma bicarbonate by a mean of 7.0 ± 2.0 (S.D.) mM after acetazolamide and by 5.6 ± 1.8 mM after NH4Cl. The ratio in the decrement of Paco2 to that of plasma bicarbonate (d Paco2/d [HC03 ]) was 1.51 in the former and 0.98 in the latter. Both drugs increased inspiratory minute ventilation (Vi) predominantly due to increased tidal volume (VT) with acetazolamide and to increased respiratory frequency (f) with NH4Cl. In HCVR, the increments in C02-ventilation slope and in ventilation at PETco2 60 mmHg after drug administration were 0.77 ± 0.51 l • min -1 • mmHg -1 and 20.0± 11.2 1/mmn with acetazolamide and 0.59 ± 0.40l • min -1 • mmHg -1 and 8.0 ± 2.8 1/mmn with NH4Cl, respectively. On the other hand, HVR both in terms of d Vi/ASao2 slope and of ventilation at Sao2 75% significantly increased after NH4Cl but not after acetazolamide administration. Thus, augmented VT and HCVR in the acetazolamide group and increased f and HVR in the NH4C1 group suggested that the central chemosensitive mechanism in the former and the peripheral chemosensitive mechanism in the latter may predominantly be responsible for the elevated ventilatory activities.

Ten climbers who participated in the Nepal-Japan Kangchenjunga Expedition (altitude, 8,478-8,586 m) in 1984 were examined for their hypercapnic and isocapnic hypoxic ventilatory responses (HCVR and HVR) at sea level before and after the expedition. Five climbers who reached an altitude higher than 8,000 m, [designated high-performance climbers (HPC)] exhibited significantly higher HVR than five climbers who did not [low-performance climbers (LPC)]. On the other hand, no significant difference in HCVR was seen between HPC and LPC. Our results were in agreement with the findings reported by Schoene et al. (J. Appl. Physiol. 56: 1478-1483, 1984) obtained in the American Medical Research Expedition to Everest in 1981. Significant depression in HVR in five climbers was found even 35-40 days after the expedition, which was accompanied by decreased arterial partial pressure of CO2 and increased pH at rest. Hence, the effect of altitude acclimatization in the climbers exposed to extreme altitude may have still persisted at the time of the postexpedition study. Our results confirmed that HRV evaluated at sea level may be used as an indicator of a climber's capability at great high altitude.

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The possible role of ventilatory control in relation to sleep apnea has not yet been clarified. We investigated the relationship between awake ventilatory drives to hypoxia and hypercapnia and sleep-disordered breathing in 21 subjects with sleep apnea syndrome. The awake hypoxic ventilatory drive, which was evaluated by occlusion pressure responses, was inversely correlated with the magnitude of maximal oxygen desaturation during sleep as well as the ratio of duration with more than 4 and 10% oxygen desaturation to total sleep time. On the other hand, the awake hypercapnic ventilatory drive was not correlated with these parameters of sleep desaturation. Apnea index and duration were not correlated with the degree of hypoxic or hypercapnic ventilatory drive, respectively. Our study concluded that sleep desaturation is better correlated with hypoxic ventilatory drive than with hypercapnic ventilatory drive in patients with sleep apnea syndrome. These results are different from the results obtained in the patients with COPD in our previous study.

We investigated the mechanisms of the beneficial effect derived from progesterone therapy for sleep apnea syndrome (SAS). Nine patients with SAS were treated for 7 days with chlormadinone acetate (CMA), a respiratory stimulant known to increase not only CO2 and hypoxic chemosensitivity but also respiratory drive response for ventilatory loading. They were examined as to sleep events and ventilatory control during wakefulness before and during CMA treatment. Apnea-hypopnea index was significantly reduced from 51.1 +/- 5.7 to 43.6 +/- 8.1 episodes/h (p less than 0.05). The ratio of desaturation time with more than 4% SaO2 fall to total sleep time was diminished in seven of nine patients, and its mean value decreased from 44.9 +/- 8.6 to 28.7 +/- 8.1% (p less than 0.05). Both hypercapnic ventilatory response (HCVR) and load response during wakefulness were significantly increased, although isocapnic hypoxic ventilatory response (HVR) was not significantly enhanced by CMA. The degree of augmentation in awake load response as well as in HCVR was positively correlated with that of improvement in sleep-disordered breathing. Moreover, patients who did not show amelioration in oxygen desaturation were found to be incapable of increasing load response despite increased HCVR. We conclude that CMA therapy for sleep apnea syndrome is effective in the patients whose load response as well as respiratory control activity are augmented during wakefulness.