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Ventilatory and mouth occlusion pressure (P0.1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (VE), tidal volume (VT), 'duty cycle' (TI/TT), mean inspiratory flow rate (VT/TI) and P0.1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at 'equivalent' levels of hypoxia and hypercapnia, i.e., at levels which produced the same P0.1 during wakefulness: an oxyhaemoglobin saturation (Sao2) of 94% during the isocapnic-hypoxic tests (PETCO2 = 42.5 +/- 1.2 mmHg) was found to be equivalent to a PETCO2 of 47.4 +/- 3.7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P0.1 were similar in all sleep stages. Sleep did not significantly modify P0.1 or breathing pattern responses to hypoxia (Sao2 = 94%). In contrast, at the 'equivalent' level of hypercapnic stimulation, P0.1 (P less than 0.05) and VE (P less than 0.01) responses were significantly impaired, particularly in REM sleep, with a decrease in VT (P less than 0.01) and VT/TI (P less than 0.05) responses. The results suggest that CO2 intracranial receptor mechanisms are more affected by sleep than the O2 peripheral receptor activity.

The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.

The presence of cimetidine in the incubation medium of rat brain mitochondria caused decreased oxygen uptake, especially during oxidative phosphorylation (state 3). This inhibition of the respiratory control and of ATP synthesis was dose-dependent. The same observations were made for hepatic mitochondria. The significance of these results is discussed in terms of both the neurological side-effects of cimetidine and its effect on regulatory mechanisms of cerebral or hepatic blood flow.

The object of this study was to assess the effect of moderate acute hypoxemia on plasma concentrations of atrial natriuretic factor (ANF), arginine vasopressin (AVP), plasma renin activity (PRA) and urinary excretion of prostaglandin E2 (UPGE2V). Eight volunteers were exposed for 2 hours to a gas mixture containing 10% O2, 4.5% CO2 and 85.5% N2. Hypoxia increased diastolic blood pressure and free water clearance. Hypoxia did not change the AVP, PRA or UPG2V, although increased ANF from 17.7 +/- 3.4 pg/mL to 27.2 +/- 1.7 pg/mL (p less than 0.005) at 120 minutes. ANF changes were closely associated with the rise in blood pressure.

Fourteen male patients with chronic bronchitis and respiratory insufficiency were monitored during nocturnal sleep by conventional polygraphy (EEG, EOG and EMG of the chin) associated with continuous recording of the mean pulmonary arterial pressure (PAP) and, in 50% of the cases, continuous measurement of O2 saturation. Six subjects were able to sleep long enough for oxygen saturation, blood gases and PAP values to be correlated with the various phases of sleep. Frequent, significant and sometimes abrupt peaks of hypoxaemia were observed; they usually, though not necessarily, occurred during paradoxical sleep. The most pronounced nocturnal changes in SaO2 were encountered in those patients who had the most severe hypoxaemia during daytime. Nocturnal fluctuations in PAP were also pronounced (with increases of more than 20 mmHg) and often paralleled changes in SaO2. Correlation between SaO2 and PAP was good in some patients ("responders") but poor or even lacking in others ("poor-or non-responders"). This preliminary study indicates that patients with chronic bronchitis may have severe exacerbations of pulmonary arterial hypertension during nocturnal sleep and warrant nocturnal oxygen therapy.

It has been reported in experimental models that acute hypoxia reduced the activity of the hepatic cytochrome P-450. The objective of the present study was to investigate in conscious dogs whether acute and chronic hypoxia will influence the disposition of theophylline. To this purpose 6 beagle dogs received 8 mg/kg i.v. of theophylline while breathing air, after acute hypoxia (PaO2 of 48.5 +/- 0.3 mmHg) and after 96 hours of hypoxia. Theophylline and metabolites, 3-methylxanthine and 1,3-dimethyluric acid, were assayed by HPLC. Theophylline volume of distribution, while breathing air, was 0.51 +/- 0.03 L/kg and was not affected by hypoxia. Theophylline metabolic and renal clearances were 1.53 +/- 0.24 and 0.18 +/- 0.04 mL/min/kg and remained constant when the dogs were hypoxic. The urinary recovery of theophylline and metabolites was not affected by acute or chronic hypoxia. It is concluded, that in the dog hypoxia does not affect the disposition of theophylline.

Sixteen patients with severe chronic obstructive pulmonary disease (COPD) (average values at the onset of O2 therapy: FEV1, 891 +/- 284 ml; PaO2, 50.2 +/- 6.6 mmHg; PaCO2, 51.0 +/- 6.4 mmHg) underwent 3 consecutive right heart catheterizations. The first was performed 47 +/- 28 months (T0) before the onset of long-term O2 therapy (LTO2). The second was performed just before the onset of LTO2 (T1). The third was performed after 31 +/- 19 months of LTO2 (T2). Oxygen therapy (15 to 18 h/day) was prescribed on the basis of usual criteria. From T0 to T1, PaO2 decreased from 59.3 +/- 9.4 to 50.2 +/- 6.6 mmHg, and mean pulmonary arterial pressure (Ppa) worsened from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.005). From T1 to T2, PaO2 was stable, whereas Ppa decreased from 28.0 +/- 7.4 to 23.9 +/- 6.6 mmHg (p less than 0.05). Pulmonary hypertension improved in 12 of the 16 patients. Before the onset of LTO2 (from T0 to T1), there was a yearly increase in Ppa of 1.47 +/- 2.3 mmHg, whereas during LTO2 a yearly decrease of 2.15 +/- 4.4 mmHg was observed, and the difference between these 2 values was highly significant. The changes in Ppa either from T0 to T1 or from T1 to T2 were not associated with concomitant changes in cardiac output or pulmonary capillary wedge pressure but were related to changes in pulmonary vascular resistance. These results suggest that LTO2 for 15 to 18 h/day can reverse the progression of pulmonary hypertension in a high percentage of patients with severe COPD, but that normalization of Ppa is rarely observed.

The efficacy and tolerance of a nasal CPAP device marketed in France (Pression +, Sefam) for the treatment of obstructive sleep apnoea syndromes have been evaluated in a co-operative trial including 12 patients. This study confirmed the efficacy of nasal CPAP on sleep parameters: total sleep time was increased; light non-REM sleep was diminished; slow-wave sleep and REM sleep were augmented; sleep apnoeas were eliminated completely or almost completely; oxygen saturation was markedly improved. At one month follow-up, most clinical features were improved; daytime blood gases showed little change but the number of red cells was decreased. On the whole, the tolerance was good in this highly motivated group of patients: eleven patients (92%) were willing to continue their home treatment with the same device. Most difficulties were due to the making of a tailored molded nasal mask and its use during sleep.

A recent study has shown in the conscious dog that hypoxia associated with respiratory acidosis could increase the in vivo distribution of digoxin in the myocardium. The aim of the present study was to evaluate in vitro the effects of hypoxia and (or) hypercapnic acidosis on the digoxin uptake. For this purpose, rat myocardium was incubated for 180 min with radiolabelled [3H]digoxin. The uptake of digoxin which was expressed in nanograms of digoxin bound per 100 mg of myocardium was decreased by hypoxia and increased by hypercapnic acidosis. The association of hypoxia and hypercapnic acidosis had no effect on the digoxin uptake, suggesting that in vitro hypoxia acts in an opposite way to hypercapnia.

The purpose of this study was to assess the relationship between the breathing pattern response to CO2 and the severity of mechanical impairment in twenty patients with COLD. The CO2 response was compared to that of a control group of twelve normal subjects. All patients had airway obstruction (FEV1 = 40 +/- 14% of predicted; means +/- SD) and hyperinflation (FRC = 154 +/- 23% of predicted). Tidal volume (VT), inspiratory and total cycle duration (TI, TT), occlusion pressure (P0.1) and endtidal PCO2 were measured at rest and during hyperoxic CO2 rebreathing. On the same day, in all patients, arterial blood gas analysis, spirometric and plethysmographic measurements were made. The slope (S) of the P0.1 response (SP 0.1) to increasing endtidal PCO2 was negatively correlated with airway resistance (r = -0.59; p less than 0.01). Although the flow response, S(VT/TI), was positively and closely correlated with SP 0.1 (r = 0.88; p less than 0.001), it also appeared to be independently influenced by obstruction (p less than 0.01). The tidal volume response, SVT, was principally correlated with inspiratory capacity (r = 0.90; p less than 0.001) and also, independently, with Vmax50 (p less than 0.01). SVT was diminished in seventeen patients, ten of whom only had a decreased S(VT/TI). The shortening in TI during hypercapnia was most marked in patients with the greatest S(P0.1), who did not have arterial hypercapnia at rest. These results suggest: that the poor VT response to CO2 in COLD patients is principally caused by a limitation in inspiratory volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

This study aimed to assess the effect of hypoxemia on theophylline disposition. Ten patients with a mean (+/- SEM) of 58 +/- 3 years with COLD (PaO2 55 +/- 1 mm Hg, PaCO2 46 +/- 2 mm Hg, and pH of 7.39 +/- 0.01) were hospitalized to have oxygen therapy. Before starting O2, they received intravenously, 4 mg/kg of theophylline over a 20-minute period; blood samples and urine were collected for six hours. The results suggested that hypoxia does not influence the disposition of theophylline or its metabolites.

Nine patients with severe, predominantly obstructive sleep apnoea syndromes were treated during one night by continuous positive pressure under polygraphic monitoring. Three patients did not tolerate the treatment for either mechanical reasons (2 cases) or ventilatory reasons (1 case). In the remaining 6 patients, continuous positive pressure resulted in reorganization of sleep and disappearance of obstructive and central apnoeic episodes. This effect was incomplete at low pressure (2 cm H2O) and complete at pressures of 6 to 10 cm H2O. The fact that continuous positive pressure was effective against both obstructive and central apnoea suggests that its mode of action is not purely mechanical but involves the central ventilatory control, probably by a reflex mechanism. In view of its effectiveness, continuous positive pressure appears to be the treatment of choice for sleep apnoea syndromes.

Ninety-three patients with severe chronic obstructive pulmonary disease (COPD) of the bronchitic (n = 74) or emphysematous type (n = 19), who all had arterial hypoxemia, underwent 2 right cardiac catheterizations in a clinical steady state, with a delay of 5 yr or more between the first and the last catheterization. No patients received long-term O2 therapy or pulmonary vasodilator drugs. Patients were divided into 2 groups according to the initial level of mean pulmonary artery pressure (Pap). Group 1 included 61 patients without initial pulmonary arterial hypertension (PAH), Pap being less than 20 mmHg; the average delay between the 2 catheterizations was 93.4 +/- 26.8 months. Group 2 included 32 patients with initial PAH (Pap greater than or equal to 20 mmHg), and the average delay was 85.0 +/- 26.0 months. The changes in Pap were small. They ranged from 15.5 +/- 2.4 to 19.6 +/- 7.0 mmHg in Group 1 (p less than 0.001) and from 25.8 +/- 5.6 to 27.8 +/- 9.5 mmHg in Group 2 (NS). The average increase in Pap was 0.65 mmHg/yr in Group 1 and 0.39 mmHg/yr in Group 2 (no statistical difference between the 2 groups). The other hemodynamic parameters (pulmonary capillary wedge pressure, right ventricle filling pressure, cardiac output) did not change. Hemodynamic "worsening," which was defined by an increase in Pap by greater than or equal to 5 mm Hg, was observed in 29% of the patients (n = 27). In these patients, there was a marked worsening of hypoxemia, which was not observed in the remaining 66 patients.(ABSTRACT TRUNCATED AT 250 WORDS)