巽 浩一郎

男性呼吸器不全患者を対象にテストステロン (T) 分泌動態を検討した. 症例をPaO₂の値により3群に分け検討を行った結果, PaO₂が60Torr 以下の呼吸不全を呈した群では, PaO₂が70Torr を越えるコントロール群と比較して, 尿中および血中T値の有意な低下が認められた. またLHRH負荷試験において, 呼吸不全を呈した群ではコントロール群と比較して, 30分後のLHの増加率の低下および個々の症例の検討でLHのピーク値出現の遅延が高率に認められた. 一方HCG負荷試験では48時間後の値に差は認められなかった. T生合成に関する17α水酸化酵素の活性を, 17α水酸化プロゲステロン/プロゲルテロンの比より推定したが, この値は低酸素血症の程度に伴い低下するのが認められた. 以上より男性呼吸不全患者においては, PaO₂低下に伴いアンドロジェン活性の低下および17α水酸化酵素活性の低下が起り, これは視床下部-下垂体系の機能低下に起因していることが示唆された.

Twelve healthy men were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, in small doses (5 mg/day), on arterial blood gas levels. Using a randomized, double-blind, crossover trial, one week of CMA administration caused a significant reduction in arterial CO2 tension (PaCO2) by 4.1 ± 2.9 (SD) mm Hg. The magnitude of the fall in PaCO2 was about the same as that obtained with dose of 50 mg per day in our previous study. These results indicate that the dosages of progestin and the effect of the drug on ventilation were not in parallel, and it may provide the idea that larger doses of progestin would not necessarily be required to stimulate ventilation.

We studied hypoxic and hypercapnic ventilatory drives in 22 eucapnic obese subjects (14 female and eight male subjects) referred for weight reduction therapy and 23 normal subjects (eight female and 15 male subjects). In the female subjects, both occlusion pressure, currently used as an indicator of ventilatory drive, and ventilatory responses to hypoxia, as well as occlusion pressure response to hypercapnia, were significantly greater in the obese than in the normal subjects however, no significant differences in these responses between male obese and male normal subjects were observed, except for the hypoxic occlusion pressure response. We also studied breathing during sleep in the obese subjects, and male predominance in abnormal breathing and oxygen desaturation was noted. These results showed that obese female subjects increased their hypoxic and hypercapnic chemosensitivities against their body mass loading, which was not evident in obese male subjects. The relatively depressed chemosensitivities of the latter may be related to disordered breathing and oxygen desaturation during sleep.

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 of apnoea 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 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 of the seven patients with varying degrees of daytime hypersomnolence had their symptoms obviously improved. There was no patient whose predominant type of apnoea was converted from the obstructive to the central type, or vice versa. In the studies of wakefulness, metabolic acidosis, an increase of arterial oxygen tension (PaO2) and a decrease of arterial carbon dioxide tension (PaCO2) were observed. The slopes of the occlusion pressure response and the ventilatory response to carbon dioxide increased, and the carbon dioxide ventilatory response line shifted to the left. It is suggested that acetazolamide cannot remove apnoea completely but has a beneficial effect in mild cases of obstructive sleep apnoea through an augmentation of central (CO2, H+) drive and a stabilising effect on ventilatory control.

Ten healthy young males were studied with a double-blind, cross-over trial to determine whether or not chlormadinone acetate (CMA), a potent synthetic progesterone, augments hypoxic chemosensi-tivity. Seven days after CMA administration, inspiratory minute volume (Vi) and tidal volume (FT) significantly increased. PaCo2 decreased by 3.0 ± 2.6 (S.D.) Torr (p&lt 0.05) and plasma bicarbonate decreased by 2.9±1.1 mM (p&lt 0.01). During CMA administration, the atmospheric hypoxic ventilatory response (HVR), assessed by minute ventilatory (ΔVt/ΔSaO2), and occlusion pressure responses (Δp2/ΔsaO2), significantly increased about 1.9 (p&lt 0.05) and 1.6 times (p&lt 0.01) compared to the placebo response, respectively. The calculated normocapnic HVR (ΔVt/ΔSaO2) increased about 2.3 times the placebo run. Hypoxic response evaluated by the withdrawal test, which represents the peripheral chemo-sensitivity without involving the influence due to secondary hypoxic depression, was about 1.7 times the placebo response (p&lt 0.05). We conclude that CMA augments hypoxic respiratory chemosensitivity. © 1987, PHYSIOLOGICAL SOCIETY OF JAPAN. All rights reserved.

We studied the effect of acetazolamide, a potent inhibitor of carbonic anhydrase, on pulmonary functions, blood gas analysis and ventilatory responses to hypoxia and hypercapnia in healthy male subjects. The following are the data obtained at 4 days after acetazolamide administration (500 mg/day), and compared with those before administration. There is no significant difference in VC, FRC, FEV(1.0%) and D(LCO). Pa(CO2), pH and (HCO3 -) decreased and Pa(O2) increased. On the average, arterial Pa(CO2) is expected to change by 1.51 Torr for a 1-meq/l chronic change in (HCO3 -). V̇1 and V(T) at rest increased while f, T1/T(TOT), V̇(CO2) and V̇(O2) at rest did not change. V(T)/T1 showed increasing tendency without statistical significance. Normocapnic hypoxic ventilatory response (HVR) increased significantly, but there was no significant change in hypocapnic HVR. Hypercapnic ventilatory response (HCVR) increased significantly in both unloaded and loaded conditions.

Recent studies have demonstrated that oxygen desaturation occurs during sleep in some patients with chronic obstructive pulmonary disease (COPD). The degree of sleep hypoventilation in COPD may be related to an inadequate chemical control of ventilation. To investigate this relationship, we compared maximal sleep changes in arterial oxygen saturation (SaO2) with the hypercapnic and hypoxic ventilatory control during wakefulness in 24 patients with COPD. Both hypercapnic and hypoxic ventilatory responses were inversely correlated with the degree of maximal sleep desaturation in rapid-eye-movement (REM) sleep. Furthermore, the level of baseline SaO2 during wakefulness was also negatively related to the magnitude of sleep desaturation. Patients with insufficient chemical control of breathing appear to have larger falls in SaO2, particularly if they have lower baseline SaO2.

A 49-year-old male was admitted with recurrent infected pulmonary cystic lesion. Chest X-ray film showed an infiltrative shadow with an air-fluid level in the right lower lobe and CT-scan showed a polycystic lesion. No arterial abnormality was found on aortography. Right lower lobectomy was carried out and pathologically, the lesion was intralobar sequestration without arterial abnormality. This case seems to support the theory that pulmonary sequestration should be considered as a bronchovascular anomaly.