Late Expiration Research Articles

Respiratory modulation of heart sound morphology

Heart sounds, the acoustic vibrations produced by the mechanical processes of the cardiac cycle, are modulated by respiratory activity. We have used computational techniques of cluster analysis and classification to study the effects of the respiratory phase and the respiratory resistive load on the temporal and morphological properties of the first (S1) and second heart sounds (S2), acquired from 12 healthy volunteers. Heart sounds exhibited strong morphological variability during normal respiration and nearly no variability during apnea. The variability was shown to be periodic, with its estimated period in good agreement with the measured duration of the respiratory cycle. Significant differences were observed between properties of S1 and S2 occurring during inspiration and expiration. S1 was commonly attenuated and slightly delayed during inspiration, whereas S2 was accentuated and its aortic component occurred earlier at late inspiration and early expiration. Typical split morphology was observed for S1 and S2 during inspiration. At high-breathing load, these changes became more prominent and occurred earlier in the respiratory cycle. Unsupervised cluster analysis was able to automatically identify the distinct morphologies associated with different respiratory phases and load. Classification of the respiration phase (inspiration or expiration) from the morphology of S1 achieved an average accuracy of 87 +/- 7%, and classification of the breathing load was accurate in 82 +/- 7%. These results suggest that quantitative heart sound analysis can shed light on the relation between respiration and cardiovascular mechanics and may be applied to continuous cardiopulmonary monitoring.

Postnatal emergence of synaptic plasticity associated with dynamic adaptation of the respiratory motor pattern

The shape of the three-phase respiratory motor pattern (inspiration, postinspiration, late expiration) is controlled by a central pattern generator (CPG) located in the ponto-medullary brainstem. Synaptic interactions between and within specific sub-compartments of the CPG are subject of intensive research. This review addresses the neural control of postinspiratory activity as the essential determinant of inspiratory/expiratory phase duration. The generation of the postinspiratory phase depends on synaptic interaction between neurones of the nucleus tractus solitarii (NTS), which relay afferent inputs from pulmonary stretch receptors, and the pontine Kölliker-Fuse nucleus (KF) as integral parts of the CPG. Both regions undergo significant changes during the first three postnatal weeks in rodents. Developmental changes in glutamatergic synaptic functions and its modulation by brain-derived neurotrophic factor may have implications in synaptic plasticity within the NTS/KF axis. We propose that dependent on these developmental changes, the CPG becomes permissive for short- and long-term plasticity associated with environmental, metabolic and behavioural adaptation of the breathing pattern.

Increased sympathetic activity in rats submitted to chronic intermittent hypoxia (CIH) is coupled to enhanced late expiratory activity

The mechanisms triggering the sympathetic overactivity in CIH rats are not understood. In the present study, we explored whether juvenile rats exposed to CIH exhibit changes in central respiratory‐sympathetic coupling. CIH was induced with 6% O2 for 40 s every 9 min, 8 h/day for 10 days. On the 11th day, awake CIH rats breathing room air showed a higher mean arterial pressure than controls (101 ± 3 vs 89 ± 3 mmHg, n = 14). Recordings of phrenic, thoracic sympathetic (tSNA), cervical vagus (cVN) and abdominal nerve (Abd) activities were made in the working heart‐brainstem preparation. During late expiration (Late E), tSNA was greater in CIH (n = 9) than in control rats (52 ± 5 vs 40 ± 3%, n = 11; P < 0.05). Moreover, CIH rats (n = 6), but not controls (n = 5), also exhibited a peak of activity in Abd during Late E with reduced post‐inspiratory activity in cVN. These observations suggest that CIH alters the breathing pattern evoking Late E activity in the Abd. We propose that this Late E discharge in CIH rats contributes with an additional excitatory synaptic drive to the sympathetic outflow and, in turn, raises arterial pressure. Further studies are required to identify the neuronal populations and the correspondent neurochemical mechanisms responsible for the altered respiratory‐sympathetic entrainment in CIH rats. Supported by CNPq and FAPESP (Brazil) and BHF (UK).

Breathing dysfunctions associated with impaired control of postinspiratory activity in Mecp2−/y knockout mice

Rett syndrome (RTT) is an inborn neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 gene (MECP2). Besides mental retardation, most patients suffer from potentially life-threatening breathing arrhythmia. To study its pathophysiology, we performed comparative analyses of the breathing phenotype of Mecp2-/y knockout (KO) and C57BL/6J wild-type mice using the perfused working heart-brainstem preparation (WHBP). We simultaneously recorded phrenic and efferent vagal nerve activities to analyse the motor pattern of respiration, discriminating between inspiration, postinspiration and late expiration. Our results revealed respiratory disturbances in KO preparations that were similar to those reported from in vivo measurements in KO mice and also to those seen in RTT patients. The main finding was a highly variable postinspiratory activity in KO mice that correlated closely with breathing arrhythmias leading to repetitive apnoeas even under undisturbed control conditions. Analysis of the pontine and peripheral sensory regulation of postinspiratory activity in KO preparations revealed: (i) prolonged apnoeas associated with enhanced postinspiratory activity after glutamate-induced activation of the pontine Kölliker-Fuse nucleus; and (ii) prolonged apnoeas and lack of reflex desensitization in response to repetitive vagal stimulations. We conclude that impaired network and sensory mediated synaptic control of postinspiration induces severe breathing dysfunctions in Mecp2-/y KO preparations. As postinspiration is particularly important for the control of laryngeal adductors, the finding might explain the upper airway-related clinical problems of patients with RTT such as apnoeas, loss of speech and weak coordination of breathing and swallowing.

Inspiratory resistances facilitate the diaphragm response to transcranial stimulation in humans

BackgroundBreathing in humans is dually controlled for metabolic (brainstem commands) and behavioral purposes (suprapontine commands) with reciprocal modulation through spinal integration. Whereas the ventilatory response to chemical stimuli arises from the brainstem, the compensation of mechanical loads in awake humans is thought to involve suprapontine mechanisms. The aim of this study was to test this hypothesis by examining the effects of inspiratory resistive loading on the response of the diaphragm to transcranial magnetic stimulation.ResultsSix healthy volunteers breathed room air without load (R0) and then against inspiratory resistances (5 and 20 cmH2O/L/s, R5 and R20). Ventilatory variables were recorded. Transcranial magnetic stimulation (TMS) was performed during early inspiration (I) or late expiration (E), giving rise to motor evoked potentials (MEPs) in the diaphragm (Di) and abductor pollicis brevis (APB). Breathing frequency significantly decreased during R20 without any other change. Resistive breathing had no effect on the amplitude of Di MEPs, but shortened their latency (R20: -0.903 ms, p = 0.03) when TMS was superimposed on inspiration. There was no change in APB MEPs.ConclusionInspiratory resistive breathing facilitates the diaphragm response to TMS while it does not increase the automatic drive to breathe. We interpret these findings as a neurophysiological substratum of the suprapontine nature of inspiratory load compensation in awake humans.

Respiratory drive in hindlimb motoneurones of the anaesthetized female cat

Anatomical studies have shown a monosynaptic projection from nucleus retroambiguus (NRA) to semimembranosus (Sm) motor nucleus in female cats, which is stronger in oestrus. Expiratory bulbospinal neurones are the best documented functional cell type in the NRA. If these cells participate in this projection, an expiratory drive would be expected in Sm motoneurones and this drive would be expected to be stronger in oestrus. In anaesthetized, paralyzed, ovariohysterectomized female cats, artificially ventilated to produce a strong respiratory drive (as monitored by phrenic nerve discharges), intracellular recordings were made from Sm motoneurones and from motoneurones in the surrounding hindlimb motor nuclei that are outside the focus of the NRA projection. The animals comprised two groups: either treated for 7 days with oestradiol benzoate (oestrous) or untreated (non-oestrous). Central respiratory drive potentials (CRDPs) were observed in most motoneurones of both groups, with amplitudes larger for the oestrous than for the non-oestrous group (1.58 ± 1.34 mV versus 0.89 ± 0.79 mV, mean ± S.D.). However, the CRDPs most often consisted of a maximum depolarization in early expiration, which declined in late expiration and into inspiration. This pattern is different from the incrementing firing pattern of most expiratory bulbospinal neurones. The CRDPs in Sm and semitendinosus motoneurones (located in the same motor column) were of similar size and frequency to CRDPs in motoneurones outside that column. The hypothesis that expiratory bulbospinal neurones are significantly involved in the projection was rejected. Alternative sources and possible functional roles for the CRDPs are discussed.

Cricothyroid muscle electrical activity during respiration and apneas in lambs

Respiratory function of the cricothyroid muscle (CT) is virtually unknown in the neonatal period. This study was aimed at assessing CT electrical activity (EMG) during respiration and central apneas in non-sedated lambs. Seven full-term and four preterm lambs were instrumented for polysomnographic recording, including EMG of the diaphragm, thyroarytenoid (TA, a glottal constrictor), posterior cricoarytenoid (PCA, the primary glottal dilator) and CT. Phasic CT EMG was usually observed during inspiration and late expiration, whereas phasic TA EMG was observed during early expiration. While TA EMG virtually disappeared in REM sleep, both inspiratory and expiratory CT EMG increased. Overall, while CT EMG was not frequently observed during central apneas in either full-term (10% of apneas, but never simultaneously with TA EMG) or preterm lambs (30% of apneas), it was associated with decreased lung volume and subglottal pressure when present alone or with PCA EMG. Our results concur with the assumption that CT behaves as a laryngeal dilator in the neonatal period.

Functional Heterogeneity Among Neurons in the Nucleus Retroambiguus With Lumbosacral Projections in Female Cats

Nucleus retroambiguus (NRA), in the caudal medulla, projects to all spinal levels. One physiological role is abdominal pressure control, evidenced by projections to intercostal and abdominal motoneurons from expiratory bulbospinal neurons (EBSNs) within NRA. The roles of NRA projections to the lumbosacral cord are less certain, although those to limb motoneurons may relate to mating behavior and those to Onuf's nucleus (ON) to maintaining continence. To clarify this we physiologically characterized NRA projections to the lumbosacral cord. Extracellular recordings were made in NRA under anesthesia and paralysis in estrus cats. Administered CO(2) gave a strong respiratory drive. Antidromic unit responses were recorded to stimulation of the contralateral ventrolateral funiculus of L(6), L(7), or sacral segments and to microstimulation in the region of semimembranosus motor nucleus or ON. All units were found at sites showing expiratory discharges. Units that showed collisions between antidromic and spontaneous spikes (all in late expiration) were identified as EBSNs. These were common from the ventrolateral funiculus (VLF) of L(6) (42.5%) or L(7) (32.9%), but rare from the sacral VLF or the motor nuclei. Antidromic latencies revealed a subthreshold respiratory drive in some non-EBSNs. This group had lower conduction velocities than the EBSNs. The remainder, with a negligible respiratory drive, had even lower conduction velocities. A new population of NRA neurons has thus been defined. They are not active even with a strong respiratory drive, but may provide most of the synaptic input from NRA to lower lumbar and sacral segments and could subserve functions related to mating behavior.

The influence of pulse and respiration on spinal cerebrospinal fluid pulsation.

The aim of the study is to elucidate the location and amount of spinal cerebrospinal fluid pulsations and to differentiate and quantify the cardiac and the respiratory influence. An echo planar imaging sequence was applied to 5 different levels of the spinal canal of 7 healthy volunteers. The amount of maximal flow and respiratory signal variation were determined by a time and frequency domain analysis, respectively. CSF pulsation was high in the anterior cervical and in the thoracolumbar spine. Respiratory influence rose by 19% at C1 and by 28% at T12. The systolic flow was elevated during late expiration and the diastolic upward movement was pronounced by early expiration. The pulsation in the lower spine seems to be related to a second motor of CSF movement because there is a rising respiratory influence and a reappearance of pulsation waves. Physiological spinal CSF pulsation contains a relevant respiratory component.

Expiratory pharyngeal airway obstruction during sleep: a multiple element model.

In patients with obstructive sleep apnea and snoring, airway obstruction during sleep is not limited to inspiration but may also occur with expiration. The aim of this study was to assess the segmental mechanics of expiratory obstruction. Experimental study of a convenience sample of 20 patients with snoring and mild obstructive sleep apnea. During sedated sleep, airflow, airway pressure measurements (supraglottic, oropharyngeal, nasopharyngeal, and nasal mask), and either supraglottic/retroglossal or retropalatal areas were simultaneously measured. Nasal continuous positive airway pressures were experimentally adjusted during single breath tests (SBTs) to modify upper airway size. Airway mechanics were evaluated during pressure drops on expiration. The predominant level of expiratory obstruction was supraglottic/retroglossal level alone (65%) or combined supraglottic/retroglossal and retropalatal (17.6%). In nonobstructed SBTs, compliance curves derived from supraglottic/retroglossal and retropalatal pressures were similar but diverged in obstructed breaths. Compliance during expiration was greater in the supraglottic/retroglossal segment compared to the retropalatal segment. Retropalatal cross-sectional size was smaller during early and late expiration on obstructed than on nonobstructed breaths independent of airway pressure measures. The rate of expiratory collapse was increased at all time points measured (P <.005) in the retropalatal segment on obstructed as compared with nonobstructed breaths. During expiration, the supraglottic/retroglossal level is obstructed more frequently and has greater compliance than the retropalatal segment. Failure of upstream pressures to describe pharyngeal obstruction supports a multi-element model of collapse. Segments interact during expiration, with increased retropalatal collapse on obstructed as compared with nonobstructed breaths. Increased collapse on expiration provides a mechanism for increased obstruction on subsequent inspiratory breaths.

Tidal Volume Forced Expiration in Asthmatic Infants: Reproducibility and Reversibility Tests

Background: The tidal volume forced expiration technique used in infants is considered as the first practical noninvasive method of assessing airway physiology in infants. However, its role has been discussed mainly due to the high variability of the derived parameters. Objectives: The aim of the study was to assess the reproducibility of a complete measurement with the tidal volume forced expiration technique in infants as measured by the maximal flow at FRC (v̇_maxFRC). A second aim was to evaluate the bronchial reversibility test in infant asthma. Methods: Thirty infants with asthma were investigated with the tidal volume forced expiration technique twice with 10 min in between and a third time 10 min after inhalation of terbutalin 0.5 mg. Results: The mean v̇_maxFRC in the first investigation was 285 ml·s^–1 (coefficient of variation 57%), unchanged in the second investigation and significantly lower than the mean predicted value of 404 ml·s^–1. The relative difference between the 2 investigations of v̇_maxFRC was mean 10.5% (SD 8.4) of the absolute v̇_maxFRC value and independent of the size of this v̇_maxFRC value. The 95% confidence interval for individual changes would then be up to 27% (mean + 2 SD). The infants with the lowest v̇_maxFRC percent predicted decreased further in v̇_maxFRC after inhalation of the bronchodilator (p < 0.05). Conclusions: The tidal volume forced expiration technique was able to measure flow at late expiration with the same reproducibility as seen with spirometry in adults, even if the flow was low. We found the technique acceptable for clinical practice and research, but the results from reversibility tests are difficult to interpret. A significant change of v̇_maxFRC would, however, be 27% or more.

Tracheal gas insufflation during late exhalation efficiently reduces PaCO(2) in experimental acute lung injury.

Tracheal gas insufflation (TGI) reduces PaCO(2) by flushing the tracheal and mechanical deadspace, and may have its maximum benefit when TGI gas is unopposed by significant expiratory gas flow. Thus, limiting TGI to the late expiratory period may diminish tracheal exposure to TGI gas while preserving the efficacy of TGI. This study examined the gas exchange consequences of such late-expiratory TGI. Randomized controlled trial, animal study. Eleven pigs. After stable lung injury was established using oleic acid 11 pigs were ventilated using a standardized lung protective strategy. Phasic expiratory TGI was applied for 30 min stages during the last 20%, 40%, 60%, and 100% of expiration in random sequence. PaCO(2) was continuously measured via an indwelling blood gas analysis system. PaCO(2) at baseline was 86.1+/-4.7 mmHg, and decreased progressively with increasing TGI duration of 20%, 40%, and 60%, but not 100%, of expiration (PaCO(2)=75.7+/-5.2, 68.8+/-3.6, 65.1+/-5.3 and 65.2+/-5.2 mmHg, respectively). For all stages the reduction in PaCO(2) relative to baseline was significant. Trends of increasing PaO(2) and airway pressure with increasing TGI duration were noted and most likely associated with a TGI-induced increase in lung volume. Under these conditions confining TGI to the final 60% of expiration achieved effective PaCO(2) reduction, not significantly different from panexpiratory TGI, while limiting exposure of the trachea to TGI gas, and reducing the potential for TGI-induced hyperinflation. These findings suggest that TGI is most effectively applied in a phasic manner in late expiration, with its duration titrated to effect.

Braking of expiratory airflow in obese pigs during wakefulness and sleep

Braking of expiratory airflow is a phenomenon prominently seen in neonates where it is thought to defend end-expiratory lung volume. This paper describes pronounced expiratory braking in an adult animal, the obese Vietnamese pot-bellied pig. Three obese pigs were chronically instrumented for recording of intrapleural pressure and bioelectric signals related to sleep. Airflow was measured by a pneumotachograph attached to a facemask. Expiratory airflow resistance was calculated for 10 consecutive expirations during wakefulness, NREM, and REM sleep. All animals demonstrated a biphasic expiratory flow pattern characterized by an initial plateau in flow at a low value followed by a rapid increase later in expiration. Airflow resistance during early expiration was on average four-fold higher than during late expiration. A striking observation was the maintenance of pronounced expiratory braking during NREM and REM sleep. Expiratory braking in these animals is likely due to laryngeal mechanisms and may serve to preserve end-expiratory lung volume or improve hemodynamics.

Firing patterns of pre-Bötzinger and Bötzinger neurons during hypocapnia in the adult rat

Controversy exists about how a coordinated respiratory rhythm is generated in the brainstem. Some authors suggest that neurons in the pre-Bötzinger complex are key to initiation of all types of breathing. While, on the other hand, it has been reported that some pre-Bötzinger neurons fail to maintain a rhythmic discharge in phase with phrenic nerve discharge during mechanical hyperventilation. Extracellular recordings were made from respiratory units in the pre-Bötzinger and Bötzinger complexes of 13 anaesthetised, paralysed and vagotomised rats. Central respiratory activity was monitored from the C5 phrenic nerve. During mechanical hyperventilation, several changes were observed in the phrenic neurogram. Firstly, the frequency and amplitude of integrated phrenic nerve discharge were reduced and reversibly stopped. Secondly, the patterned discharges changed from an augmenting to a variety of non-augmenting patterns in 53 of 60 cases. In some cases ( n=9) we observed that the pattern appeared to have two components, an early short duration discharge followed by a longer duration discharge. Respiratory units also started to show different firing patterns during mechanical hyperventilation. In general, they were divided into those units that fired tonically ( n=28) and units that became silent ( n=32), before phrenic nerve discharge ceased coincidently with complete apnoea. Of particular interest were those expiratory–inspiratory units in the pre-Bötzinger complex ( n=8) that narrowed their firing period towards late expiration and early inspiration during mechanical hyperventilation. Given their firing features, it is possible that these expiratory–inspiratory units may participate in generation of the early inspiratory component of phrenic nerve discharge.

Detection of a relation between respiration and CSF pulsation with an echoplanar technique.

The flow of cerebrospinal fluid (CSF) through the aqueduct was studied with an echoplanar imaging technique. Images (1024) of a slice perpendicular to the aqueduct were acquired with a repetition time of 107 msec and a flip angle of 90 degrees. This imaging technique is very sensitive for flow into the selected slice, although a quantitative assessment of flow velocities is not possible. Simultaneously with the image data acquisition, data from a pulse oximeter and a respiration belt were recorded. For each data point, a delay time to the preceding cardiac pulse was determined from the recorded pulse wave. The signal intensities could then be assigned to the cardiac cycle. Each cardiac interval was assigned to one of eight respiratory phases, and an average signal curve during the cardiac interval was calculated for each respiration phase. The evaluation showed to signal maxima within the cardiac interval, which could be identified as a downward flow at 10% and an upward flow at 80% of the cardiac pulse interval by measurements with additional saturation pulses. In examinations of 22 healthy volunteers, an influence of respiration on the flow through the aqueduct was found. In spite of interindividual variability, comparable effects could be observed in all volunteers. In the late expiration phase the caudally directed flow was at its maximum, whereas the cranially directed flow was maximal in the post-inspiration phase.

Inhibition of inspiratory motor output by high-frequency low-pressure oscillations in the upper airway of sleeping dogs.

1. We utilized a chronically tracheostomized, unanaesthetized dog model to study the reflex effects on inspiratory motor output of low-amplitude, high-frequency pressure oscillations (HFPOs) applied to the isolated upper airway (UA) during stable non-rapid eye movement (NREM) sleep. 2. HFPOs (30 Hz and +/-2 to +/-4 cmH2O) were applied via a piston pump during eupnoea, inspiratory resistive loading and tracheal occlusion. 3. When applied to the patent UA during expiration, and especially during late expiration, HFPOs prolonged expiratory time (TE) and tonically activated the genioglossus muscle EMG. When applied to the patent UA during inspiration, HFPOs caused tonic activation of the genioglossus muscle EMG and inhibition of inspiratory motor output by either: (a) a shortening of inspiratory time (TI), as inspiration was terminated coincident with the onset of HFPOs; or (b) a prolonged TI accompanied by a decreased rate of rise of diaphragm EMG and rate of fall of tracheal pressure. These effects of HFPOs were observed during eupnoea and inspiratory resistive loading, but were maximal during tracheal occlusion where the additional inhibitory effects of lung inflation reflexes were minimized. 4. During eupnoea, topical anaesthesia of the UA abolished the HFPO-induced prolongation of TE, suggesting that the response was mediated primarily by mechanoreceptors close to the mucosal surface; whereas the TE-prolonging effects of a sustained square wave of negative pressure (range, -4.0 to -14.9 cmH2O) sufficient to close the airway were preserved following anaesthesia. 5. These results demonstrate that high-frequency, low-amplitude oscillatory pressure waves in the UA, similar to those found in snoring, produce reflex inhibition of inspiratory motor output. This reflex may help maintain UA patency by decreasing the collapsing pressure generated by the inspiratory pump muscles and transmitted to the UA.

Aspiration of airway dead space. A new method to enhance CO2 elimination.

Alveolar ventilation and CO2 elimination during mechanical ventilation can be enhanced by reducing dead-space ventilation. Aspiration of gas from the dead space (ASPIDS) is a new principle, according to which gas rich in CO2 during late expiration is aspirated through a channel ending at the distal end of the tracheal tube. Simultaneously, fresh gas injected into the inspiratory line fills the airway down to the same site. We hypothesized that ASPIDS would allow a reduction of tidal volume (VT) and airway pressure (Paw). To test our hypothesis we studied six anaesthetized and mechanically ventilated pigs (24 +/- 4 kg). The intention was to decrease VT while keeping PaCO2 constant by using ASPIDS. VT was reduced by decreasing the minute ventilation (V E) in two steps, of 1.8 L/min (VE - 1.8) and 2.2 L/min (VE - 2.2), respectively, and by increasing respiratory rate (RR) from 20 to 46 breaths/min. At ASPIDS, peak Paw was reduced by 35% at VE - 1.8 and at VE - 2.2 (p < 0.001), and by 20% at an RR of 46 (p < 0.01). PaCO2 was maintained or reduced at ASPIDS. No intrinsic positive end-expiratory pressure developed. Arterial blood pressure and heart rate were unaffected. The results show that ASPIDS allows a reduction in VT and Paw while PaCO2 is kept constant. ASPIDS does not lead to problems associated with jet streams of gas or with gas humidification, and can be developed as a safe technique.

Changes in left ventricular contractility with the phase of respiration

The end-systolic wall stress ( σ es)–velocity of circumferential fiber shortening ( V cfsc) relation was defined during the respiratory cycle, in order to obtain a totally noninvasive measure of left ventricular contractility. Eight young, healthy subjects were studied with echocardiography and calibrated carotid pulse tracings, while performing slow paced breathing. Left ventricular σ es vs. V cfsc relation was determined by fitting linear regression line to data points obtained at different times during the respiratory cycle. Data are given as mean±1SD. Left ventricular σ es and V cfsc exhibited small but significant changes during the respiratory cycle: σ es was highest in late inspiration (56.9±4.8 g/cm 2) and lowest in late expiration (49.2±3.7 g/cm 2); inversely, V cfsc was lowest during late inspiration (1.18±0.17 circ/s) and highest during late expiration (1.34±0.20 circ/s). The relation was significant in each subject ( r=−0.64±0.13) and remained inverse and significant, when it was determined separately for inspiration and expiration ( r=−0.61±0.17 and −0.68±0.12, respectively). At identical end-systolic wall stress, the velocity of shortening was greater during inspiration then expiration, suggesting that contractility was reduced during the expiratory phase. The reduced expiratory contractility might reflect increased vagal influence on the ventricular myocardium.

Detection of endotracheal tube obstruction by analysis of the expiratory flow signal.

Acute obstruction of endotracheal tubes (ETT) increases airway pressure, decreases tidal volume, increases the risk of dynamic hyperinflation by prolonging the duration of passive expiration, and prevents reliable calculation of tracheal pressure. We propose a computer-assisted method for detecting ETT obstruction during controlled mechanical ventilation. The method only requires measurement of the expiratory flow. Computer simulation; prospective study in two cases; retrospective study in one case and in seven patients with the adult respiratory distress syndrome (ARDS). Laboratory of the Section of Experimental Anaesthesiology (University of Freiburg); surgical adult intensive care units in a university hospital (University of Basel) and in a university affiliated hospital (Zentralklinikum Augsburg). 3 patients with partial ETT or bronchial obstructions and 7 ARDS patients. Expiratory flow was measured using a pneumotachograph and integrated to obtain expiratory volume. The time-constant of passive expiration (tauE) as a function of expired volume [tauE(V(E)) function] was calculated from the expiratory volume/flow curve. We investigated the tauE(V(E)) function of data obtained from: (1) computer simulation of mechanically ventilated homogeneous and inhomogeneous lungs intubated with ETTs of different sizes; (2) one patient with an artificial ETT obstruction of 7.5 and 25% of the cross-sectional area of the ETT (case 1); (3) one patient with ETT obstruction due to secretions (case 2); (4) one patient with acute bronchial constriction (case 3); (5) seven ARDS patients who showed an increase in airway resistance of more than 2 cm H2O x s/l. It was found that an ETT obstruction caused an increase in tauE in early expiration (at high flow), whereas tauE in late expiration was virtually unchanged. The reason for this is the flow dependency of the increase in ETT resistance produced by ETT obstruction. Unlike ETT obstruction, an increase in pure airway resistance produced an increase in tauE throughout expiration. An ETT obstruction can be reliably distinguished from an increase in pure airway resistance by a characteristic pattern change in the tauE(V(E)) function, which can be detected easily even by an automated pattern recognition system.

Bötzinger-complex expiratory neurons monosynaptically inhibit phrenic motoneurons in the decerebrate rat.

We examined respiratory neurons in the Bötzinger complex of the medulla oblongata in 18 vagotomized, paralyzed, ventilated, and decerebrated rats and tested the hypothesis that bulbospinal expiratory neurons in this region monosynaptically inhibit phrenic motoneurons. First, we surveyed the types of respiratory neurons found in the Bötzinger complex; only 11 of the 98 (approximately 11%) examined were bulbospinal, and all discharged only during late expiration (E2), usually with an augmenting discharge frequency (AUG). Then, we examined the spinal projections of 34 E2-AUG neurons using antidromic activation and found that all projected as far as the C4 or C5 segments of the spinal cord but no further caudally. Most (30, approximately 88%) had only unilateral projections, the majority (25, approximately 83%) ipsilateral, but 4 neurons (approximately 12%) had bilateral projections. Their axons could be antidromically activated at low currents (less than 10 microA) in the dorsal-lateral part of the spinal cord at the C2-3 border; 0.5-1.2 mm (mean+/-SD 0.84+/-0.23 mm) below the dorsal surface and 0.7-1.5 mm (1.19+/-0.25 mm) lateral from the midline. We sought evidence for connections from bulbospinal E2-AUG neurons to 118 phrenic motoneurons by computing spike-triggered averages (STAs) of their intracellular potentials triggered by the action potentials of 38 unilaterally-projecting E2-AUG neurons. Resting phrenic motoneuron membrane potentials ranged from -40 to -75 mV (-56+/-8 mV) and fluctuations with the respiratory cycle from 7 to 20 mV (14+/-4 mV). Of the 118 STAs computed, hyperpolarizations were evident in 18 (approximately 15%) STAs, evoked by 11 of 38 (approximately 29%) E2-AUG neurons. Their amplitudes varied from 35 to 550 microV (105+/-113 microV), 10-90% fall times from 0.4 to 0.9 ms (0.63+/-0.17 ms), and half-amplitude widths from 1.3 to 3.2 ms (2.0+/-0.52 ms). Most (16/95, approximately 17%) of the STAs that displayed hyperpolarizations were associated with ipsilateral trigger neurons but some (2/23, approximately 9%) resulted from contralateral trigger neurons. We conclude that Bötzinger-complex, expiratory neurons project to the C4 and/or C5 segments of the cervical spinal cord but no further caudal. Their axons are located dorsolaterally in the upper cervical segments of the spinal cord, and they monosynaptically inhibit phrenic motoneurons during the late part of expiration.