Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barré syndrome.

We conducted a prospective controlled study of the clinical and biological determinants of the mental status abnormalities in 139 patients with Guillain-Barré syndrome (GBS) and 55 patients without GBS placed in the intensive care unit (ICU controls). There were mental status changes in 31% of GBS patients and in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included vivid dreams (19%), illusions (30%, including an illusory body tilt), hallucinations (60%, mainly visual) and delusions (70%, mostly paranoid). They appeared a median 9 days after disease onset (range 1-40 days, during the progression or the plateau of the disease), and lasted a median 8 days. Seven (16%) patients experienced the symptoms before their admission to the ICU. Hallucinations were frequently hypnagogic, occurring as soon as the patients closed their eyes. Autonomic dysfunction, assisted ventilation and high CSF protein levels were significant risk factors for abnormal mental status in GBS patients. CSF hypocretin-1 (a hypothalamic neuropeptide deficient in narcolepsy) levels, measured in 20 patients, were lower in GBS patients with hallucinations (555 +/- 132 pg/ml) than in those without (664 +/- 71 pg/ml, P = 0.03). Since the mental status abnormalities had dream-like aspects, we examined their association with rapid eye movement sleep (REM sleep) using continuous sleep monitoring in 13 GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic ICU controls without hallucinations. Although sleep was short and fragmented in all groups, REM sleep latency was shorter in GBS patients with hallucinations (56 +/- 115 min) than in GBS patients without hallucinations (153 +/- 130 min) and in controls (207 +/- 179 min, P < 0.05). In addition, sleep structure was highly abnormal in hallucinators, with sleep onset in REM sleep periods (83%), abnormal eye movements during non-REM sleep (57%), high percentages of REM sleep without atonia (92 +/- 22%), REM sleep behaviour disorders and autonomic dysfunction (100%), reminiscent of a status dissociatus. The sleep abnormalities, that were almost absent in non-hallucinated GBS patients, were not exclusively related to ICU conditions, since they also appeared out of ICU, and were reversible, disappearing when the mental status abnormalities vanished while the patients were still in ICU. In conclusion, the mental status abnormalities experienced by GBS patients are different from the ICU delirium, are strongly associated with autonomic dysfunction, severe forms of the disease and possibly with a transitory hypocretin-1 transmission decrease. Sleep studies suggest that mental status abnormalities are wakeful dreams caused by a sleep and dream-associated disorder (status dissociatus).

Expiratory flow limitation as a determinant of orthopnea in acute left heart failure.

OBJECTIVES: To assess the contribution of expiratory flow limitation (FL) in orthopnea during acute left heart failure (LHF). BACKGROUND: Orthopnea is typical of acute LHF, but its mechanisms are not completely understood. In other settings, such as chronic obstructive pulmonary disease, dyspnea correlates best with expiratory FL and can, therefore, be interpreted as, in part, the result of a hyperinflation-related increased load to the inspiratory muscles. As airway obstruction is common in acute LHF, postural FL could contribute to orthopnea. METHODS: Flow limitation was assessed during quiet breathing by applying a negative pressure at the mouth throughout tidal expiration (negative expiratory pressure [NEP]). Flow limitation was assumed when expiratory flow did not increase during NEP. Twelve patients with acute LHF aged 40-98 years were studied seated and supine and compared with 10 age-matched healthy subjects. RESULTS: Compared with controls, patients had rapid shallow breathing with slightly increased minute ventilation and mean inspiratory flow. Breathing pattern was not influenced by posture. Flow limitation was observed in four patients when seated and in nine patients when supine. In seven cases, FL was induced or aggravated by the supine position. This coincided with orthopnea in six cases. Only one out of the five patients without orthopnea had posture dependent FL. Control subjects did not exhibit FL in either position. CONCLUSIONS: Expiratory FL appears to be common in patients with acute LHF, particularly so when orthopnea is present. Its postural aggravation could contribute to LHF-related orthopnea.

[Removal of a tracheostomy in ventilator-dependent patients with neuromuscular disease]. / Sevrage de la trachéotomie chez des patients neuromusculaires dépendants d'une ventilation mécanique.

BACKGROUND: Ventilation via a tracheostomy is effective but very restricting in patients with neuromuscular disease. Return to non-invasive ventilation (NIV) is possible but this is not common practice, partly for want of standardised procedures ensuring a safe transition. METHODS: A procedure for transfer of ventilation via a tracheostomy to a mask has been developed based on the literature and local experience (feasibility of NIV, absence of laryngo-tracheal lesions, adequate leak compensation, effective cough). It has been tested in three patients with severe but stable neuromuscular disorders (chronic polyneuropathy in two cases and progressive spinal amyotrophy on one). RESULTS: The three patients were able to be extubated and established on domiciliary ventilation in 6,7 and 10 days, at the end of which all were discharged home. After 4 months in two cases and 6 months in the other no significant complications developed, the respiratory status under NIV was comparable to that previously under tracheostomy and the patients were satisfied with the change. CONCLUSION: The proposed algorithm seems to permit a rapid and safe transition from a tracheostomy to a mask. Large scale studies are needed to verify this concept and subsequently to identify within which group a similar approach may be correctly applied.

[Tracheostomy in intensive care: impact on prognosis and the influence of underlying chronic respiratory insufficiency]. / Trachéotomie en réanimation: pronostic et rôle d'une insuffisance respiratoire chronique.

INTRODUCTION: Numerous uncertainties remain concerning the place of tracheostomy in intensive care. Reluctance to perform tracheostomy is common, particularly in the presence of pre-existing chronic respiratory insufficiency (CRI), but some data suggest there may be benefits. The objective of this study was to evaluate the influence of tracheostomy on mortality in both intensive care and hospital, and to study the role of pre-existing CRI. MATERIAL AND METHODS: In a retrospective study of the records of 2901 patients admitted over a period of 5 years 882 were identified who had been intubated and ventilated. 127 patients who had had tracheostomies (T+) were compared with 755 who had not (T-), and with a sub-group of T- patients (T-app) matched for severity on admission (SAPSII). RESULTS: ICU and hospital mortality were significantly less in the T+ than the T-patients (28 vs 52% and 42 vs 59%) and the duration of stay was longer. This was equally true when matched for severity on admission when T+ were compared with T app (28 vs 49% and 42 vs 59%). Pre-existing CRI did not influence the outcomes of the tracheostomised patients, regardless of whether the CRI was obstructive, restrictive or neuro-muscular. CONCLUSIONS: Tracheostomy can, in certain groups of artificially ventilated patients and in certain care settings, be associated with a reduction in hospital mortality.

Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis.

BACKGROUND: Patients with PD can have disabling visual hallucinations associated with dopaminergic therapy. Sleep disorders, including vivid dreams and REM sleep with motor behaviors (RBD), are frequent in these patients. METHODS: The association of hallucinations and REM sleep both at night and during the day was examined in 10 consecutive nondemented patients with long-standing levodopa-responsive PD and hallucinations. Seven patients presented with paranoia and paranoid delusions. Overnight sleep recordings and standard multiple daytime sleep latency test were performed. The results were compared to those of 10 similar patients with PD not experiencing hallucinations. RESULTS: RBD was detected in all 10 patients with hallucinations and in six without. Although nighttime sleep conditions were similar in both groups, hallucinators tended to be sleepier during the day. Delusions following nighttime REM period and daytime REM onsets were observed in three and eight of the hallucinators, and zero and two of the others. Daytime hallucinations, coincident with REM sleep intrusions during periods of wakefulness, were reported only by hallucinators. Postmortem examination of the brain of one patient showed numerous Lewy bodies in neurons of the subcoeruleus nucleus, a region that is involved in REM sleep control. CONCLUSION: The visual hallucinations that coincide with daytime episodes of REM sleep in patients who also experience post-REM delusions at night may be dream imagery. Psychosis in patients with PD may therefore reflect a narcolepsy-like REM sleep disorder.

Improvement of sleep architecture in PD with subthalamic nucleus stimulation.

High-frequency stimulation of the subthalamic nucleus (STN) was used to investigate the relationship of sleep disorders with motor handicap in PD. In 10 insomniac patients with PD, stimulation reduced nighttime akinesia by 60% and completely suppressed axial and early morning dystonia, but did not alleviate periodic leg movements (n = 3) or REM sleep behavior disorders (n = 5). Total sleep time increased by 47%; wakefulness after sleep onset decreased by 51 minutes. Insomnia in patients with PD may predominantly result from nighttime motor disability.

Parkinson's disease and sleepiness: an integral part of PD.

OBJECTIVE: To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents. METHODS: The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists. RESULTS: Sleep latency was 6.3 +/- 0.6 minutes (normal >8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal <10). A narcolepsy-like phenotype (> or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index >15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices. CONCLUSIONS: In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.

Chronic hiccups and sleep.

To explore the effect of sleep on hiccups, we studied eight patients aged 20-81 years, all males with chronic hiccups lasting 7 days to 7 years, by means of overnight polysomnography. The incidence of new bouts of hiccups and the likelihood of hiccups being present were both highest in wakefulness and became progressively lower through stages I-IV of slow wave sleep (SWS) to rapid eye movement sleep (REMS). There was a significant tendency for hiccups to disappear at sleep onset and REMS onset. Of all 21 bouts of hiccups that were observed to stop, 10/21 did so during an apnea or hypopnea. Frequency of hiccups within a bout slowed progressively from wakefulness through the stages of SWS to REMS. For the whole group, mean frequency decreased significantly from wakefulness [(25.6 +/- 12.1), (mean +/- SD)] to sleep onset or stage I (22.3 +/- 12.2). Sleep latency was increased from 8 +/- 16.3 minutes when hiccups were absent to 16.35 +/- 19.9 minutes when it was present. Sleep efficiency was poor because of long waking periods, and there were deficiencies of both SWS and REMS. Hiccups themselves were not responsible for any arousals or awakenings. We conclude that neural mechanisms responsible for hiccups are strongly influenced by sleep state and that hiccups disrupt sleep onset but not established sleep.

Assessment of the motor pathway to the diaphragm using cortical and cervical magnetic stimulation in the decision-making process of phrenic pacing.

BACKGROUND: Phrenic nerve pacing is a recognized substitute to positive pressure ventilation via tracheotomy in patients with high cervical cord lesions or central hypoventilation. Although its indications are infrequent, reliable strategies need to be used in the determinations of patients who may benefit from this treatment; contraindications should be carefully respected. STUDY OBJECTIVES: To determine whether modern and noninvasive means to study the motor pathway to the diaphragm, namely cortical magnetic stimulation (CxMS) and cervical magnetic stimulation (CMS), can contribute to the selection of patients who may benefit from phrenic pacing. DESIGN AND SETTING: Prospective study (18 months), on a consecutive basis, of patients referred for possible phrenic pacing to a 10-bed ICU associated with a respiratory neurophysiology laboratory. PATIENTS: Seven patients (high cervical cord injury, n = 5; central hypoventilation following neurosurgery, n = 1; idiopathic acquired central hypoventilation, n = 1). INTERVENTION, MEASUREMENTS, AND RESULTS: Electromyography of the diaphragm and transdiaphragmatic pressure were assessed in response to CxMS and CMS. In three cases, no interruption of the corticodiaphragmatic pathway was evidenced, the decision of pacing was postponed, and the patients eventually recovered a spontaneous breathing activity. In two cases, the diagnosis of irreversible peripheral phrenic dysfunction was reached and pacing was denied. In two cases, complete interruption of the corticodiaphragmatic pathway and integrity of peripheral conduction led to the decision of phrenic pacemaker implantation. CONCLUSION: CxMS and CMS can be used to refine the assessment of patients proposed for phrenic pacing. CxMS can possibly identify those in whom there is a possibility for eventual recovery, and therefore substantiate a decision to postpone the pacing.

Airway occlusion pressure.

Airway occlusion pressure has been used in the past two decades for assessing output of the respiratory controller. It gives a measurement of a weighted sum of the effect of all respiratory muscles active at a given time and, unlike ventilation or tidal volume, does not depend on the resistance or compliance of the respiratory system. In anesthetized subjects or animals, it gives a tracing of the time course of respiratory neuromuscular output through the respiratory cycle, modified by elimination of most phasic vagal stretch receptor feedback and perhaps slightly by activation of some chest wall reflexes. The original postulate that an occluded inspiration would be isometric and the measured pressure free from losses due to force-length and force-velocity has been shown to be incorrect. The volume at which occlusion takes effect, distortions of the chest wall during the maneuver, tonic vagal input, and strength of the muscles must be taken into account when the data are interpreted. Brief occlusions [pressure at 0.1 s (P0.1)] are useful in measuring output in the very first part of inspiration in conscious subjects but must be treated with a great deal of caution. They are most reliable when end-expiratory volume remains constant and there are no important phase lags between flow and pressure. Allowance may be necessary for damping of the pressure signal on its passing through the compliant upper airway. Changes in P0.1 may often be due to changes in the shape of the driving pressure wave without a proportionate change in overall output. The technique remains useful when its limitations are recognized. Because of its simplicity, it can be easily and usefully applied to a range of clinical investigations.

In vivo length-force relationship of canine diaphragm.

Diaphragmatic length was measured by sonomicrometry and transdiaphragmatic pressure (Pdi) by conventional latex balloons in eight dogs anesthetized with pentobarbital sodium under passive conditions and during supramaximal phrenic stimulation. The passive length-pressure relationship indicates that the crural part of the diaphragm is more compliant than the costal part. With supramaximal stimulation the costal diaphragm showed a length-pressure relationship similar in shape to in vitro length-tension curves previously described for the canine diaphragm. The crural part has a smaller pressure-length slope than the costal part in the length range from 80% of optimum muscle length (Lo) to Lo. At supine functional residual capacity (FRC) the resting length (LFRC) of the costal and crural diaphragms are not at Lo. The costal part is distended to 105% of Lo, and crural is shortened to 92% of Lo. Tidal shortening will increase the force output of costal while decreasing that of the crural diaphragm. The major forces setting the passive supine LFRC are the abdominal weight (pressure) and the elastic recoil of the lungs. The equilibrium length (resting length of excised diaphragmatic strips) was 79 +/- 3.6% LFRC for the costal diaphragm and 87 +/- 3.9% LFRC for the crural diaphragm. Similar shortening was obtained in the upright position, indicating passive diaphragmatic stretch at supine LFRC.

Facilitation of the diaphragm response to transcranial magnetic stimulation by increases in human respiratory drive.

The human respiratory neural drive has an automatic component (bulbospinal pathway) and a volitional component (corticospinal pathway). The aim of this study was to assess the effects of a hypercapnia-induced increase in the automatic respiratory drive on the function of the diaphragmatic corticospinal pathway as independently as possible of any other influence. Thirteen healthy volunteers breathed room air and then 5 and 7% hyperoxic CO2. Cervical (cms) and transcranial (tms) magnetic stimulations were performed during early inspiration and expiration. Transdiaphragmatic pressure (Pdi) and surface electromyogram of the diaphragm (DiEMG) and of the abductor pollicis brevis (apbEMG) were recorded in response to cms and tms. During inspiration, Pdi,cms was unaffected by CO2, but Pdi,tms increased significantly with 7% CO2. During expiration, Pdi,cms was significantly reduced by CO2, whereas Pdi,tms was preserved. DiEMG,tms latencies decreased significantly during early inspiration and expiration (air vs. 5% CO2 and air vs. 7% CO2). DiEMG,tms amplitude increased significantly in response to early expiration-tms (air vs. 5% CO2 and air vs. 7% CO2) but not in response to early inspiration-tms. DiEMG,cms latencies and amplitudes were not affected by CO2 whereas 7% CO2 significantly increased the apbEMG,cms latency. The apbEMG,tms vs. apbEMG,cms latency difference was unaffected by CO2. In conclusion, increasing the automatic drive to breathe facilitates the response of the diaphragm to tms, during both inspiration and expiration. This could allow the corticospinal drive to breathe to keep the capacity to modulate respiration in conditions under which the automatic respiratory control is stimulated.

Cervical magnetic stimulation as a method to discriminate between diaphragm and rib cage muscle fatigue.

Inspiratory muscle fatigue can probably determine hypercapnic respiratory failure. Diaphragm fatigue is detected by electrical phrenic stimulation (ELS), but there is no simple tool to assess rib cage muscle (RCM) fatigue. Cervical magnetic stimulation (CMS) costimulates the phrenic nerves and RCM. We reasoned that changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMS and ELS should be different after selective diaphragm vs. RCM fatigue. Five volunteers performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and RCM. Baseline Pdi,twELS and Pdi,twCMS were 28.57 +/- 1.68 and 32.83 +/- 2.92 cmH2O. After selective diaphragm loading, Pdi,twELS and Pdi,twCMS were reduced by 39 and 26%, with comparable decreases in gastric pressure twitch (Pga,tw). Esophageal pressure twitch (Pes,tw) was better preserved with CMS. Therefore Pes,tw/Pga,tw was lower with ELS than CMS (-1.24 +/- 0.16 vs. -1.73 +/- 0.11, P = 0.05). After selective RCM loading, there was no diaphragm fatigue, but Pes,twCMS was significantly reduced (-30%). These findings support the role of rib cage stiffening by CMS-related RCM contraction in the ELS-CMS differences and suggest that CMS can be used to assess RCM fatigue.

Cervical magnetic stimulation: a new painless method for bilateral phrenic nerve stimulation in conscious humans.

Assessing diaphragmatic contractility is a common goal in various situations. This assessment is mainly based on static or dynamic maximal voluntary maneuvers and twitch transdiaphragmatic pressures (Pdi) obtained by stimulation of the phrenic nerves (PS). PS eliminates the central components of diaphragmatic activation, but the available techniques of PS remain subject to some limitations. Transcutaneous PS is painful, and needle PS is potentially dangerous. Time-varying magnetic fields can stimulate nervous structures without pain and without adverse effects. In six subjects, we have studied cervical magnetic stimulation (CMS) as a method of PS. We have compared the stimulated Pdi (Pdistim) with the maximal Pdi obtained during static combined expulsive-Mueller maneuver (Pdimax) and with the Pdi generated during a sniff test (Pdisniff). CMS produced twitch Pdi averaging 33.4 +/- 9.7 cmH2O. Pdistim/Pdimax and Pdistim/Pdisniff were 24 +/- 6 and 41 +/- 14%, respectively. These values are comparable to those obtained in other studies with transcutaneous PS. They were highly reproducible in all the subjects. Electromyographic data provided evidence of bilateral maximal stimulation. CMS is a nonspecific method and may stimulate various nervous structures. However, diaphragmatic contraction was elicited by stimulation of the phrenic trunk, since the phrenicodiaphragmatic latencies (less than 7 ms) were in the range of values reported with direct stimulation of the trunk. Cocontraction of neck muscles, including the sternomastoid, was present, but its influence in the CMS-induced Pdi seems minimal. We conclude that magnetic stimulation is an easy, well-tolerated, reproducible safe, and valuable method to assess phrenic conduction and diaphragmatic twitch response.

Putative projection of phrenic afferents to the limbic cortex in humans studied with cerebral-evoked potentials.

Respiratory sensations may rely in part on cortical integration of respiratory afferent information. In an attempt to study such projections, we recorded evoked potentials at scalp and cervical sites in 10 normal volunteers undergoing transcutaneous phrenic stimulation (0.1-ms square pulses, intensity liminal for diaphragmatic activation, series of 600 shocks at 2 Hz). A negative cerebral component of peak latency (12.79 +/- 0.54 ms; N13) was constant, and a negative spinal component (7.09 +/- 1.04 ms; N7) could also be recorded, all results being reproducible over time. Monitoring of cardiac frequency, skin anesthesia, and stimulation adjacent to the phrenic nerve made the phrenic origin of N7 and N13 the foremost hypothesis. Increasing stimulation frequency and comparison with median nerve stimulation provided arguments for the neural nature of the signals and their cerebral origin. Recordings from intracerebral electrodes in a patient showed a polarity reversal of the evoked potentials at the level of the cingulate gyrus. In conclusion, phrenic stimulation could allow one to study projections of phrenic afferents to the central nervous system in humans. Their exact site and physiological meaning remain to be clarified.

Comparison of magnetic and electrical phrenic nerve stimulation in assessment of phrenic nerve conduction time.

Cervical magnetic stimulation (CMS), a nonvolitional test of diaphragm function, is an easy means for measuring the latency of the diaphragm motor response to phrenic nerve stimulation, namely, phrenic nerve conduction time (PNCT). In this application, CMS has some practical advantages over electrical stimulation of the phrenic nerve in the neck (ES). Although normal ES-PNCTs have been consistently reported between 7 and 8 ms, data are less homogeneous for CMS-PNCTs, with some reports suggesting lower values. This study systematically compares ES- and CMS-PNCTs for the same subjects. Surface recordings of diaphragmatic electromyographic activity were obtained for seven healthy volunteers during ES and CMS of varying intensities. On average, ES-PNCTs amounted to 6.41 +/- 0.84 ms and were little influenced by stimulation intensity. With CMS, PNCTs were significantly lower (average difference 1.05 ms), showing a marked increase as CMS intensity lessened. ES and CMS values became comparable for a CMS intensity 65% of the maximal possible intensity of 2.5 Tesla. These findings may be the result of phrenic nerve depolarization occurring more distally than expected with CMS, which may have clinical implications regarding the diagnosis and follow-up of phrenic nerve lesions.

Linkage of hiccup with heartbeat.

We explored a possible link between the cardiac cycle and the timing of recurrent hiccups in 10 patients with chronic, intractable hiccups. Recordings made during daytime naps in a sleep laboratory included sleep state; electrocardiogram; and respiration by means of a thermistor to detect airflow, bands around the rib cage and abdomen to assess expansion, and a bipolar surface electrode electromyogram over parasternal intercostal muscles. Hiccups could be detected on the abdominal bands and the parasternal electromyogram. The time of occurrence of each hiccup and each R wave in a continuous tracing of 100 or more hiccups were recorded and analyzed together with semiquantitive estimates of the phase of hiccup respiration. Whereas the hiccup rate ranged from approximately one-third to one-eighth of heart rate and was more variable than heart rate, hiccups showed a tendency, stronger in some subjects than others, to occur in midsystole. Variation in R-wave-R-wave (R-R) interval in association with hiccups was found in five patients. In three of these patients, hiccups were synchronized with respiration so that the cyclic change in R-R interval posthiccup could be explained as sinus arrhythmia, but, in two patients, the hiccups were not synchronized with respiration, so that hiccups are most likely responsible for the variation in heart rate. Also, the variation of R-R interval with hiccups suggests that there is some phasic autonomic efferent activity associated with hiccups.

Viscoelastic behavior of lung and chest wall in dogs determined by flow interruption.

Pulmonary and chest wall mechanics were studied in six anesthetized paralyzed dogs, by use of the technique of rapid airway occlusion during constant flow inflation. Analysis of the pressure changes after flow interruption allowed us to partition the overall resistance of the lung (Rl) and chest wall (Rw) and total respiratory system (Rrs) into two components, one (Rinit) reflecting in the lung airway resistance (Raw), the other (delta R) reflecting primarily the viscoelastic properties of the pulmonary and chest wall tissues. The effects of varying inspiratory flow and inflation volume were interpreted in terms of frequency dependence of resistance, by using a spring-and-dashpot model previously proposed and substantiated by Bates et al. (Proc. 9th Annu. Conf. IEEE Med. Biol. Soc., 1987, vol. 3, p. 1802-1803). We observed that 1) Raw and Rw,init were nearly equal and small relative to Rl and Rw (both were unaffected by flow); 2) Rrs,init decreased slightly with increasing volume; 3) both delta Rl and delta Rw decreased with increasing flow and increased with increasing lung volume. These changes were manifestations of frequency dependence of delta R, as it is predicted by the model; 4) Rrs, Rl, and Rw followed the same trends as delta R. These results corroborate data previously reported in the literature with the use of different techniques to measure airways and pulmonary tissue resistances and confirm that the use of Rl to assess bronchial reactivity is problematic. The interrupter techniques provides a convenient way to obtain Raw values, as well as analogs of lung and chest wall tissue resistances in intact dogs.

Effect of negative expiratory pressure on respiratory system flow resistance in awake snorers and nonsnorers.

In spontaneously breathing subjects, intrathoracic expiratory flow limitation can be detected by applying a negative expiratory pressure (NEP) at the mouth during tidal expiration. To assess whether NEP might increase upper airway resistance per se, the interrupter resistance of the respiratory system (Rint,rs) was computed with and without NEP by using the flow interruption technique in 12 awake healthy subjects, 6 nonsnorers (NS), and 6 nonapneic snorers (S). Expiratory flow (V) and Rint,rs were measured under control conditions with V increased voluntarily and during random application of brief (0.2-s) NEP pulses from -1 to -7 cmH(2)O, in both the seated and supine position. In NS, Rint,rs with spontaneous increase in V and with NEP was similar [3.10 +/- 0.19 and 3.30 +/- 0.18 cmH(2)O x l(-1) x s at spontaneous V of 1.0 +/- 0.01 l/s and at V of 1.1 +/- 0.07 l/s with NEP (-5 cmH(2)O), respectively]. In S, a marked increase in Rint,rs was found at all levels of NEP (P < 0.05). Rint,rs was 3.50 +/- 0.44 and 8.97 +/- 3.16 cmH(2)O x l(-1) x s at spontaneous V of 0.81 +/- 0.02 l/s and at V of 0.80 +/- 0.17 l/s with NEP (-5 cmH(2)O), respectively (P < 0.05). With NEP, Rint,rs was markedly higher in S than in NS both seated (F = 8.77; P < 0.01) and supine (F = 9.43; P < 0.01). In S, V increased much less with NEP than in NS and was sometimes lower than without NEP, especially in the supine position. This study indicates that during wakefulness nonapneic S have more collapsible upper airways than do NS, as reflected by the marked increase in Rint,rs with NEP. The latter leads occasionally to an actual decrease in V such as to invalidate the NEP method for detection of intrathoracic expiratory flow limitation.

Application of negative expiratory pressure during expiration and activity of genioglossus in humans.

The application of negative expiratory pressure (NEP) at end expiration has been shown to cause reflex-mediated activation of the genioglossus muscle in awake humans. To test whether a reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after the onset of expiration and during the end-expiratory pause, was assessed in 10 normal awake subjects at rest. The raw and integrated surface electromyogram of the genioglossus (EMGgg) was recorded with airflow and mouth pressure under control conditions and with NEP ranging from -3 to -10 cmH2O. Intraoral EMGgg was also recorded under the same experimental conditions in two subjects. The application of NEP at the end-expiratory pause elicited a consistent reflex response of EMGgg in seven subjects with a mean latency of 68 +/- 5 ms. In contrast, when NEP was applied at the onset of expiration, EMGgg reflex activity was invariably observed in only one subject. No relationship was found between steady increase or abrupt fall in expiratory flow and the presence or the absence of a reflex activity of genioglossus during sudden application of NEP at the beginning of expiration. Our results show that a reflex activity of genioglossus is elicited much more commonly during application of NEP at the end rather than at the onset of expiration. These findings also suggest that when NEP is applied in early expiration to detect intrathoracic flow limitation the absence of upper airways narrowing does not imply the occurrence of a reflex-mediated activation of genioglossus and vice versa.