Treatment of obstructive sleep apnea with a simple CPAP device.

PURPOSE: CPAP is the "gold standard" treatment for obstructive sleep apnea (OSA). Current CPAP models have developed additional functions including automatic CPAP and pressure relief. However, CPAP adherence has not improved over the last three decades. Many patients in low-income countries cannot afford these CPAP devices. A novel simple CPAP device with a fixed pressure without pressure controller was developed. METHODS: Manual CPAP pressure titration was performed in 127 patients with OSA. Six patients with a titration pressure higher than 11 cmH2O and 14 patients who could not tolerate CPAP were excluded, leaving 107 participating in the following 2 studies. In study one, 54 of 107 patients were treated by both conventional fixed CPAP and simple CPAP in random order. In the second study, another 53 patients were treated by both autoCPAP in automatic function and simple CPAP in random order. Simple CPAP was fixed at 10 cmH2O, 8 cmH2O, and 6 cmH2O for patients whose titration pressure was between 9-10, 7-8, and ≤ 6 cmH2O, respectively. Conventional fixed CPAP device was set exactly the same as manual titration pressure. RESULTS: All patients whose manual titration pressure ≤ 10 cmH2O were effectively treated by simple CPAP (AHI 40.7 ± 2.3 events/h before vs 2.5 ± 0.3 events/h after, p < 0.001). Patients expressed similar preferences for simple CPAP, autoCPAP, and conventional fixed CPAP (p > 0.05). CONCLUSIONS: We conclude that a novel simple CPAP is an alternative treatment for most patients with OSA, which may widen access to CPAP therapy in the developing countries because of its low cost.

ICU shift related effects on sleep, fatigue and alertness levels.

BACKGROUND: Shift work may lead to suboptimal sleep resulting in impaired alertness, and lowered performance levels, all of which can lead to medical errors. AIMS: To examine fatigue, sleepiness and behavioural alertness prospectively in a tertiary level Australian intensive care unit (ICU). METHODS: All full-time doctors providing 24-h resident cover on a 12-h day and 12-h night shift roster were invited to participate in this study. Data collected included Epworth Sleepiness Scale (ESS), sleep and awake history, Samn-Perelli Fatigue (SPF) Scale, Karolinska Sleepiness Scale (KSS) and iOS-based Psychomotor Vigilance Test (behavioural alertness). Data about medical emergency team (MET) shifts were collected separately as they were perceived to be busier shifts. RESULTS: Twenty-nine ICU doctors participated in this study for a consecutive 6-week period. At baseline the median (interquartile range (IQR)) ESS was 5 (3-9). Day shift leads to an increase in fatigue and sleepiness (both P < 0.01). Night shift leads to worsening in fatigue, sleepiness and psychomotor vigilance (all P < 0.01). MET shifts had a lower psychomotor vigilance than non-MET shifts. The difference in the psychomotor vigilance was mostly due to the difference in recorded lapses and response time. CONCLUSIONS: Shift work ICU doctors experience high levels of fatigue and sleepiness. Night shifts also lead to decreased vigilance. This is even more evident in doctors working MET shifts. These factors may lead to errors. Optimal rostering may reduce these effects and improve patient safety.

Economic evaluation of diagnostic sleep studies for obstructive sleep apnoea in the adult population: a systematic review.

Evidence regarding the cost-effectiveness of limited channel tests compared to laboratory and home polysomnography (PSG) in diagnosing obstructive sleep apnoea (OSA) is unclear. Eligible studies were systematically sought across the following databases: MEDLINE, PsychINFO, SCOPUS, CINAHL, Cochrane, Emcare, Web of Science and ProQuest. Title and abstracts were screened before full-text review. Only full and partial economic evaluations reporting at least one economic outcome were included. A standardised template was used for critical appraisal and data extraction. Relevant findings were summarised using a qualitative approach adhering to economic reporting standards. Literature searches identified 999 non-duplicate abstracts, where 85 studies were retrieved for full-text review. The number of studies that met eligibility criteria and were included in the final analyses was 35, of which 31 investigated Level 3 and four assessed Level 4 tests. Based on the dominance ranking framework, both Level 3 and Level 4 tests were cost-effective compared to PSG. Although study designs and methodologies differ broadly, the findings indicated that using limited channel diagnostic sleep tests for OSA is associated with lower costs and non-inferior health outcomes relative to PSG. Limited channel tests also resulted in shorter waiting times and improved access to diagnostic services for patients with OSA. PROSPERO REGISTRATION NUMBER: CRD42020150130.

Economic evaluation of diagnostic sleep studies for obstructive sleep apnoea: a systematic review protocol.

BACKGROUND: Obstructive sleep apnoea (OSA) is a significant public health problem affecting a large proportion of the population and is associated with adverse health consequences and a substantial economic burden. Despite the existence of effective treatment, undiagnosed OSA remains a challenge. The gold standard diagnostic tool is polysomnography (PSG), yet the test is expensive, labour intensive and time-consuming. Home-based, limited channel sleep study testing (levels 3 and 4) can advance and widen access to diagnostic services. This systematic review aims to summarise available evidence regarding the cost-effectiveness of limited channel tests compared to laboratory and home PSG in diagnosing OSA. METHODS: Eligible studies will be identified using a comprehensive strategy across the following databases from inception onwards: MEDLINE, PsychINFO, SCOPUS, CINAHL, Cochrane Library, Emcare and Web of Science Core Collection and ProQuest databases. The search will include a full economic evaluation (i.e. cost-effectiveness, cost-utility, cost-benefit, cost-consequences and cost-minimisation analysis) that assesses limited channel tests and PSG. Two reviewers will screen, extract data for included studies and critically appraise the articles for bias and quality. Meta-analyses will be conducted if aggregation of outcomes can be performed. Qualitative synthesis using a dominance ranking matrix will be performed for heterogeneous data. DISCUSSION: This systematic review protocol uses a rigorous, reproducible and transparent methodology and eligibility criteria to provide the current evidence relating to the clinical and economic impact of limited channel and full PSG OSA diagnostic tests. Evidence will be examined using standardised tools specific for economic evaluation studies. TRIAL REGISTRATION: PROSPERO (CRD42020150130).

Economic evaluation of cognitive behavioural therapy for insomnia (CBT-I) for improving health outcomes in adult populations: A systematic review.

Cognitive behavioural therapy for insomnia (CBT-I) is a promising intervention with established efficacy, yet evidence of its cost-effectiveness remains unclear. Systematic searches were conducted in Medline, Psychinfo, ProQuest, Cochrane, Scopus, CINAHL, Web of Science and Emcare. Titles and abstracts were screened against eligibility criteria, and studies reporting full economic evaluations of CBT-I in adult populations were included and examined in detail. Study characteristics were extracted using a standardised template. Quantitative measures and relevant findings were summarised using a qualitative approach following recommended reporting standards. 1,168 non-duplicate articles were identified, of which 44 were selected for full-text review. Seven full economic evaluations of CBT-I in adult populations met the inclusion criteria and were incorporated in the final synthesis. Using the dominance ranking framework to compare cost and outcomes, CBT-I was cost-effective compared to pharmacotherapy or no treatment. The limited number of studies included in this review implies that caution should be exercised when interpreting these results. Future studies are encouraged to employ longer time-horizons and larger sample sizes to enable better determination of sustained cost and outcomes changes. Prospero registration number: CRD42019133554.

Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.

BACKGROUND: Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD. METHOD: A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood. RESULTS: 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour. CONCLUSIONS: Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life. TRIAL REGISTRATION NUMBER: ACTRN12605000205639.

Effects of moderate sleep deprivation and low-dose alcohol on driving simulator performance and perception in young men.

STUDY OBJECTIVE: To determine the combined effects of sleep restriction and low-dose alcohol on driving simulator performance, EEG, and subjective levels of sleepiness and performance in the mid-afternoon. DESIGN: Repeated measures with 4 experimental conditions. Normal sleep without alcohol, sleep restriction alone (4 hours) and sleep restriction in combination with 2 different low blood alcohol concentrations (0.025 g/dL and 0.035 g/dL). SETTING: Sleep Laboratory, Adelaide Institute for Sleep Health. PARTICIPANTS: Twenty-one healthy young men, aged 18-30 years, mean (+/-SD) = 22.5(+/-3.7) years, BMI = 25(+/-6.7) kg/m2; all had normal sleep patterns and were free of sleep disorders. MEASUREMENTS: Participants completed a 70-minute simulated driving session, commencing at 14:00. Driving parameters included steering deviation, braking reaction time, and number of collisions. Alpha and theta EEG activity and subjective driving performance and sleepiness were also measured throughout the driving task. RESULTS: All measures were significantly affected by time. Steering deviation increased significantly when sleep restriction was combined with the higher dose alcohol. This combination also resulted in a significant increase in alpha/theta EEG activity throughout the drive, as well as greater subjective sleepiness and negative driving performance ratings compared to control or sleep restriction alone. DISCUSSION: These data indicate that combining low-dose alcohol with moderate sleep restriction results in significant decrements to subjective alertness and performance as well as to some driving performance and EEG parameters. This highlights the potential risks of driving after consumption of low and legal doses of alcohol when also sleep restricted.

COPD care in Saudi Arabia: physicians' awareness and knowledge of guidelines and barriers to implementation.

OBJECTIVE: To assess Saudi physicians' awareness and knowledge about chronic obstructive pulmonary disease (COPD) guideline recommendations. METHODS: Cross-sectional study including physicians involved in COPD care in five hospitals in the Eastern Province of Saudi Arabia. The level of physicians' knowledge was considered as satisfactory (score > 80%), fair (score 50-80%) or poor (<50% of total score). RESULTS: Among the 44 physicians included in the study, the mean ± standard deviation knowledge score was 29.5 ± 4.2 out of 45 points (65.5%). Most physicians appeared to be unaware of any COPD guidelines (n = 27, 61.4%), and reported not adhering to guidelines (n = 28, 63.6%). CONCLUSION: Saudi physicians' knowledge about Global Initiative for Chronic Obstructive Lung Disease guidelines was assessed as fair. It is therefore highly recommended to increase physicians' awareness and knowledge about COPD-related guidelines.

A functional autoantibody in narcolepsy.

Narcolepsy is widely believed to have an autoimmune basis, but conventional immunological approaches have failed to detect a serum autoantibody marker. Since cholinergic hyperactivity is a feature of narcolepsy-cataplexy, we transferred IgG from nine patients with narcolepsy and nine healthy controls to mice and assessed the effect on smooth muscle contractile responses to cholinergic stimulation. IgG from all narcolepsy patients significantly enhanced bladder contractile responses to the muscarinic agonist carbachol and to neuronally released acetylcholine compared with control IgG (p<0.0001), whereas contraction of the sympathetically innervated vas deferens was unaltered. Our findings provide direct evidence for the autoimmune hypothesis of narcolepsy.

Treatment of obstructive sleep apnea syndrome with nasal continuous positive airway pressure.

To help define the place of nasal continuous positive airway pressure (n-CPAP) treatment in a general sleep apnea population we studied 12 of 13 consecutively diagnosed patients with obstructive sleep apnea syndrome (OSAS). The immediate effects of n-CPAP were tested during a nighttime sleep study divided into two approximately equal parts (control and n-CPAP). Nasal CPAP of 5-10 cm H2O decreased apnea index (apneas per hour of sleep) (control 35.1, n-CPAP 5.7; p less than 0.001) and significantly improved oxyhemoglobin saturation (SaO2). The effect was independent of body weight and the presence of cardiorespiratory complications. However, in three patients with lung disease and markedly elevated PaCO2, significant sleep-related hypoxemia persisted at the relatively low pressures required to open the upper airway. Long-term home-based n-CPAP was offered to 11 patients. (One patient was considered unsuitable because of persisting profound sleep-related hypoxemia). Seven patients consented and were followed for periods ranging from 1 to 18 months. All patients reported dramatic reversal of daytime hypersomnolence; three complained of minor nasal stuffiness but compliance was good and only one stopped using the mask (after 12 months). Apnea index decreased following home use of n-CPAP (before 35.9, after 18.1; p less than 0.01) but overall respiratory instability (apnea + hypopnea) and SaO2 were not significantly improved. It is concluded that n-CPAP is a highly effective means of preventing upper airway occlusion in OSAS and, except for some patients with coexisting lung disease, it totally reverses the accompanying gas exchange disturbance. Long-term home-based n-CPAP therapy is acceptable to a majority of patients, is free of serious side effects, and appears to result in a partial reversal of the underlying breathing disorder.

Ventilatory responses to sustained eucapnic hypoxia in healthy males during wakefulness and NREM sleep.

The effects of sustained eucapnic hypoxia (SEH, 20 minutes SaO2, approximately 80%) on ventilation and supraglottic airflow resistance (Rua) plus genioglossal (gg) and diaphragmatic (di) electromyograms (EMGs) were compared during wakefulness and nonrapid eye movement (NREM) sleep in six healthy normal male subjects. Early augmentation of ventilation was followed by decline or roll-off in both states. The augmentation of ventilation was less in sleep than wakefulness (e.g., after 5 minutes hypoxia, 140% and 167% of baseline, respectively, p < 0.05). This appeared to be due to three factors: 1) sleep-related increases in Rua [the ventilatory responses to SEH (sleep vs. awake) were inversely related to changes in Rua (sleep vs. awake) (p < 0.05)], 2. reduced central neural drive (inspiratory phasic EMG di after 5 minutes SEH, 111% and 121% of baseline, p < 0.05), and 3) failure to increase respiratory frequency during SEH sleep. There was also a nonsignificant trend to a biphasic response in EMG gg and a small increase in Rua during SEH.

Acute cardiovascular responses to arousal from non-REM sleep during normoxia and hypoxia.

STUDY OBJECTIVES: There is uncertainty concerning the relative contribution of arousal, chemoreceptor stimulation, and their potentially interactive effects, to the acute cardiovascular changes observed during sleep in patients with sleep-disordered breathing. The purpose of this study was to compare cardiovascular responses (heart rate, skin blood flow, and pulse transit time, a non-invasive measure of arterial wall stiffness) to auditory induced arousal from stage 2 sleep under conditions of normoxia and overnight mild hypoxia. DESIGN: Randomised crossover. SETTING: Sleep Disorders Unit in a 270-bed teaching hospital. PARTICIPANTS: Eleven healthy male subjects. INTERVENTIONS: Subjects slept wearing a facemask and breathed room air (one night; SaO2 approximately 98%) or an hypoxic gas mixture (two nights; SaO2 approximately 92%). Once in stage 2 sleep, subjects were administered one of 10 auditory tones (500 Hz, range 54-90 dB, 5-sec duration) via earphones or a sham tone (recording with no tone). MEASUREMENTS AND RESULTS: Cardiovascular responses were examined beat-by-beat for 20 seconds before and 30 seconds after auditory tones associated with arousals (3-10 second EEG changes) and after sham tones. Sleep efficiency and the percentage of sleep spent in each stage were not different between hypoxia and normoxia nights. Baseline heart rate was elevated on hypoxia nights compared with normoxia nights (59.5+/-1.7 vs. 54.4+/-1.6 b x min(-1), p=0.007). Heart rate, pulse transit time, and skin blood flow showed significant changes after arousal consistent with rapid parasympathetic withdrawal and sympathetic nervous system activation. No changes were observed after sham tones. There were no differences in time course or magnitude of cardiovascular responses between hypoxia and normoxia nights. CONCLUSIONS: We conclude that while mild hypoxia stimulates autonomic activity it does not augment the cardiovascular response to arousal from stage 2 sleep in normal subjects.

Portable computerized polysomnography in attended and unattended settings.

STUDY OBJECTIVE: We compared the validity of a new portable polysomnographic recorder against a laboratory-based polysomnographic system from the same manufacturer. DESIGN AND PATIENTS: Simultaneous, full polysomnographic recordings from the portable device (PSGP) and the laboratory-based system (PSGL) were obtained using separate sets of sensors on 20 patients referred for investigation of sleep apnea. SETTING: After initial optimization of signals, the portable device was left unattended in 10 of the patients (to simulate home studies), while in the other 10 the signals were reviewed on a laptop computer screen and adjustments to electrode or sensor placement made as needed during the studies. Recordings were manually scored by a technologist blinded to the origin of the data. MEASUREMENTS AND RESULTS: The quality of signals was comparable between the PSGP and PSGL studies, apart from a slight decrease in respiratory signal quality during PSGP studies that led to reduced confidence in respiratory event scoring. SaO2 signal loss was also greater in unattended PSGP. There was good agreement between PSGP and PSGL for sleep variables and the apnea-hypopnea index (r=0.99). The periodic limb movement index was slightly lower during unattended PSGP. Blinded physician assessment of the records led to a recommendation for repeat studies due to poor signal quality in one (10%) attended and one (10%) unattended portable recording. There was no significant discordance between PSGP and PSGL in the final diagnostic formulations. CONCLUSION: Portable polysomnography is a viable alternative to laboratory-based polysomnography and may be improved further by better sensor attachment.

A comparison of two long-acting vasoselective calcium antagonists in pulmonary hypertension secondary to COPD.

UNLABELLED: STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and may predict mortality in this disorder. We have compared the pulmonary vasodilator effects, dose-response characteristics, and tolerability of two calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10 patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH. DESIGN: Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg), increasing weekly for 3 weeks, in a randomized investigator-blinded crossover manner with a 1-week wash-out period between the two treatments. MEASUREMENTS: Doppler measurements of pulmonary hemodynamics were made on the seventh day of treatment at each drug dose. Lung function, arterial blood gases, and adverse events were also monitored weekly. RESULTS: A dose-dependent decline of pulmonary artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a significant decrease in PAP compared with baseline (20% amlodipine, 17% felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that were similar for both drugs, but did not reach statistical significance compared with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance and increase in oxygen delivery with amlodipine and felodipine ER. Lung function and blood gas values were stable throughout. Side effects (headache and ankle edema) were less frequent during amlodipine treatment (p<0.05). CONCLUSIONS: Both amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg, are effective pulmonary vasodilators in COPD patients with PH. Their dose-response characteristics are similar, but amlodipine treatment was associated with fewer side effects.

Validation of new pulsed Doppler echocardiographic techniques for assessment of pulmonary hemodynamics.

In preparation for a vasodilator study on chronic obstructive pulmonary disease (COPD), we investigated the reliability of recently described pulsed Doppler techniques for estimating pulmonary artery pressure (PAP) and cardiac output (CO). Our aims were to determine the following: (1) the imaging success rate for pulsed Doppler measurements; (2) the repeatability of the measurements, and interobserver and intraobserver variability; and (3) the accuracy of Doppler compared with catheter measurements. Doppler studies were attempted in 81 patients (cardiac disease [23], COPD [22], sleep apnea [32], and normal subjects [4]). Suitable images were obtained in 68 subjects (84 percent) and in 76 subjects (94 percent) for PAP and CO estimations, respectively. The lowest imaging success rates were in COPD patients (68 percent for PAP and 86 percent for CO estimation). Repeatability of the techniques was assessed in four cardiac patients and three healthy volunteers by performing four replicate studies in each subject over 1 h. Intrasubject coefficient of variation was < 10 percent for PAP and < 5 percent for CO. The intraobserver variability for Doppler estimation of systolic and mean PAP was 5.5 percent and 5.8 percent, respectively. The corresponding values for interobserver variability were 6.7 percent and 6.2 percent. Intraobserver and interobserver variability for "nongeometric" method of estimating CO was 5.1 percent and 5.9 percent, respectively. Agreement was good between catheter-measured and Doppler-estimated PAP in the 27 patients tested (cardiac [19] and COPD [8]) for both mean and systolic pressures (r = 0.96 and r = 0.97, respectively). The correlations between thermodilution and Doppler estimations of CO in eight COPD patients were 0.77 ("geometric" technique) and 0.97 ("nongeometric" technique). We conclude that pulsed Doppler techniques can be used to obtain accurate and reproducible quantitative information on pulmonary hemodynamics in a wide range of patients. Suitable Doppler images can be obtained in more than two thirds of COPD patients.

Felodipine improves pulmonary hemodynamics in chronic obstructive pulmonary disease.

Pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis. Reduction of pulmonary artery pressure in COPD by prolonged oxygen treatment has been shown to be associated with increased survival. In an attempt to find a suitable pharmacologic method of reducing pulmonary artery pressure and pulmonary vascular resistance in COPD, we enrolled 13 stable pulmonary-hypertensive, hypoxemic COPD patients in a study to test the effects of felodipine, a relatively new, vascular-selective calcium antagonist. Doppler echocardiography was used to estimate pulmonary artery pressure and cardiac output before treatment, 2, 7, and 12 weeks during felodipine treatment (10 to 20 mg/d), and after a 1-week placebo washout period. Measurements of lung function, arterial blood gases, and exercise capacity during an incremental bicycle ergometer test were also performed at intervals during the study period. Three patients withdrew from the study and of the remaining 10, 8 had some side effects of medication (peripheral edema or headache) that improved either spontaneously or following a reduction in drug dose. In the 10 patients who completed the study (8 male; mean age, 67 years), felodipine resulted in significant reductions in mean pulmonary artery pressure (22 percent) and total pulmonary (vascular) resistance (30 percent) and increases in cardiac output (15 percent) and stroke volume (13 percent) compared with baseline measurements and those taken after placebo washout. These effects were sustained over the 12 weeks of felodipine treatment. There was no adverse effect of felodipine treatment on pulmonary gas exchange at rest or during exercise and no change in lung function or exercise capacity. We conclude that in pulmonary hypertensive, hypoxemic COPD patients, felodipine substantially improves pulmonary hemodynamics.

Tachykinins mediate hypocapnia-induced bronchoconstriction in guinea pigs.

The aim of this study was to determine whether hypocapnia causes bronchoconstriction by releasing tachykinins (TKs) from C-afferent nerves in airways. Hypocapnia-induced bronchoconstriction (HIBC) was induced in anesthetized vagotomized guina pigs by ventilating lungs with a heated humidified hypocapnic gas mixture for 15 min after sudden circulatory arrest. The intensity of bronchoconstriction was assessed by calculating changes in dynamic compliance and by measuring the relaxation lung volume at the completion of experiments. Visualization of the airways by tantalum bronchography showed constriction of segmental bronchi with relative sparing of more proximal airways. Hypocapnia-induced bronchoconstriction was prevented by prior administration of salbutamol aerosol. Three experimental interventions were used to investigate the role of TKs in HIBC: 1) repeated capsaicin injections to deplete airway sensory nerves of TKs, 2) treatment with phosphoramidon, an inhibitor of enkephalinase, the main enzyme responsible for TK inactivation, and 3) topical airway anesthesia. Capsaicin pretreatment markedly attenuated the hypocapnia-induced changes in dynamic compliance (P less than 0.0005) and relaxation lung volume (P less than 0.0002), whereas phosphoramidon augmented these changes (P less than 0.02, P less than 0.03, respectively). Topical anesthesia of airways with lignocaine postponed the onset of bronchoconstriction, whereas the longer-acting, more lipid-soluble local anesthetic, bupivacaine, almost completely prevented HIBC. We conclude that, in the guinea pig lung, HIBC is mediated by TKs that are released after the activation of bronchial axonal reflexes.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Comparison of effects of sustained isocapnic hypoxia on ventilation in men and women.

Sleep-related respiratory disturbances are more common in men than in premenopausal women. This might, in part, be due to different susceptibilities to the respiratory depressant effects of hypoxia. Therefore, we compared ventilation during 10 min of baseline room-air breathing and 20-min sustained isocapnic hypoxia (fractional inspired O2 = 11%, arterial saturation of O2 approximately 80%) followed by 10 min of breathing 100% O2 in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O2 (10 min) and averaged. Inspired minute ventilation (VI) after 2 min of hypoxia was the same in men and women [131 +/- 6.1% baseline for men, 136 +/- 7.7% baseline for women; not significant (NS)] and declined to the same level after 20 min (115 +/- 5.0% baseline for men, 116 +/- 6.6% baseline for women; NS) associated with a similar decline in inspiratory time and tidal volume. Breathing frequency did not change. VI decreased transiently during subsequent 100% O2 breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall in VI was significantly greater than that observed during control hyperoxia experiments in men but not in women. We conclude that ventilatory responses to sustained isocapnic hypoxia do not differ between awake healthy men and women in the follicular phase of their menstrual cycle. However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.