In the present study, respiratory drives to chemical stimuli and peripheral chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS). The effects of oral administration of domperidone, a selective dopamine D 2 -receptor antagonist, were also examined, to study the respiratory effects of endogenous dopamine on peripheral chemoreceptors.Sixteen patients with OSAS and nine normal control subjects were studied. Respiratory responses to hypercapnia and hypoxia were measured using the rebreathing method and isocapnic progressive hypoxia method, respectively. The hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% O 2 under mild hypercapnic hypoxic conditions (end-tidal oxygen and carbon dioxide tensions &8.0 kPa and 5.3±6.7 kPa, respectively), was used to evaluate peripheral chemosensitivity.In the patients with OSAS, ventilatory responses to hypercapnia and hypoxia were significantly decreased compared with those of control subjects. Hypoxic withdrawal tests showed that peripheral chemosensitivity was significantly lower in patients with OSAS than in normal subjects. Hypercapnic ventilatory response and peripheral chemosensitivity were enhanced by administration of domperidone in the patients with OSAS, although no changes in either of these were observed in the control subjects. The hypoxic ventilatory response and peripheral chemosensitivity in the patients with OSAS were each significantly correlated with severity of hypoxia during sleep.These findings suggest that peripheral chemosensitivity in patients with obstructive sleep apnoea syndrome may be decreased as a result of abnormality in dopaminergic mechanisms and that the reduced chemosensitivity observed in patients with obstructive sleep apnoea syndrome may affect the severity of hypoxia during sleep. Eur Respir J 1999; 13: 418±423.

A 61-year-old man, who suffered from Charcot-Marie-Tooth disease (CMT) for 44 years, was evaluated for the respiratory disorder. He had diaphragmatic dysfunction induced by phrenic nerve disturbance. In this patient, central type apnea and hypopnea related to dia phragmatic weakness occurred during REM sleep, which induced accessory inspiratory muscle inhibition. Respiratory muscle dysfunction had not been generally recognized in CMT until recently, but its significance should be emphasized. (Internal Medicine 31: 1267-1270, 1992 Key words: phrenic nerve disturbance, apnea, hypopnea, hypoxemia Case ReportA 61-year-old man was sent to our hospital for further evaluation of a respiratory disorder during sleep which was pointed during a hospital stay in November 1988. He had Charcot-Marie-Tooth disease (CMT) since age 17 and had been admitted to the previous hospital since 1973. He did not note any dyspnea or general fatigue but complained of sleeplessness for the previous 5 years. There was no history of cardiopulmonary disease. Neuro muscular disease in his family history was negative. His general status appeared to be fair, though he was not able to walk by himself, but could move using a wheelchair. His height was 168cm and weight was 49kg. No deformities of the chest wall and the vertebra were observed. Pulse was regular and the rate was 72/min. Blood pressure was 140/70mmHg. Respiration rate was 16/min. In the supine position, the abdominal wall retracted paradoxically in the inspiratory phase. No edema or clubbed finger sign were revealed. Peripheral cyanosis was recognized in the toes. Consciousness was clear and there was no problem with his intelligence. Cranial nerves were intact. Speech and swallowing were performed without any disturbance. Muscles in the bilateral hands and forearms were atrophied and claw hands were recognized. All muscles below the bilateral middle third of the thigh had atrophied showing the appearance of "stork legs." The feet were short and showed arched deformities called upes caves." The strength of the atrophied muscles was diminished and deep tendon reflexes were absent except for trace reflexes in the bilateral biceps and triceps muscles. There was no trace of pathological reflex, fasciculation or tremor. There was slight disturbance of deep sensation below the level of the tenth thoracic vertebra and touch and pain sensations were manifestly disturbed in the lower limbs, especially in the feet. The chest X-ray film showed a slight elevation of the left diaphragm, and a normal cardiac silhouette. An impairment of bilateral diaphragm movement was recognized fluoroscopically. In the laboratory data on admission, peripheral blood, biochemistry, urinalysis and the thyroid function test were normal. There was no evidence of the diabetic metabolic disorders. In the pulmonary function test, vital capacity was 3,040ml in the sitting position. On the contrary, it de creased to 2,010ml in the supine position. Especially, expiratory reserve volume which was 1,240ml in the sittig positio...

The effects of changing perfusate flow on lung nitric oxide (NO) production and pulmonary arterial pressure (Ppa) were tested during normoxia and hypoxia and after N(G)-monomethyl-L-arginine (L-NMMA) treatment during normoxia in both blood- and buffer-perfused rabbit lungs. Exhaled NO (eNO) was unaltered by changing perfusate flow in blood-perfused lungs. In buffer-perfused lungs, bolus injections of ACh into the pulmonary artery evoked a transient increase in eNO from 67 +/- 3 (SE) to 83 +/- 7 parts/billion with decrease in Ppa, whereas perfusate NO metabolites (pNOx) remained unchanged. Stepwise increments in flow from 25 to 150 ml/min caused corresponding stepwise elevations in eNO production (46 +/- 2 to 73 +/- 3 nl/min) without changes in pNOx during normoxia. Despite a reduction in the baseline level of eNO, flow-dependent increases in eNO were still observed during hypoxia. L-NMMA caused declines in both eNO and pNOx with a rise in Ppa. Pulmonary vascular conductance progressively increased with increasing flow during normoxia and hypoxia. However, L-NMMA blocked the flow-dependent increase in conductance over the range of 50-150 ml/min of flow. In the more physiological conditions of blood perfusion, eNO does not reflect endothelial NO production. However, from the buffer perfusion study, we suggest that endothelial NO production secondary to increasing flow, may contribute to capillary recruitment and/or shear stress-induced vasodilation.

A 31-year-old womanvisited an out-patient clinic, because of low-grade fever and general fatigue. She was referred to our hospital and admitted for examination of an abnormal shadow which had been found on the chest radiograph. She had experienced faint right lateral chest pain several times on the deep inspirations. Chest radiography showeda mass shadowwith calcification in the right lower lung field on the mediastinal side. Chest radiographic computed tomography showed a 6x6 cm tumor in the right lung field. There were low-density areas with septae inside the tumor. Bone scintigraphy showed extremely high uptake of "mTc-HMDP in the tumor. After surgical resection and pathological examination, we concluded that the tumor was an extensively calcified benign hemangiomaof the diaphragm. (Internal Medicine 39: 576-578, 2000)

We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.