Early Expiratory Phase Research Articles

Effects of Manual Rib Cage Compressions on Mucus Clearance in Mechanically Ventilated Pigs.

Manual rib cage compression is a chest physiotherapy technique routinely used in clinical practice. However, scientific evidence remains scarce on the effects of manual rib cage compression on airway clearance and oxygenation in mechanically ventilated patients. Anesthetized pigs were intubated via the trachea and mechanically ventilated. To create atelectasis, artificial mucus was infused into the airway. Each pig was randomly assigned to 1 of 2 groups: closed suctioning alone (control group, 7 pigs), or manual rib cage compression combined with closed suctioning (manual rib cage compression group, 8 pigs). Hard and brief rib cage compression synchronized with early expiratory phase was tested. Mucus clearance and oxygenation were assessed after the intervention. Sequential changes of hemodynamics were assessed after the intervention. During hard manual rib cage compression, the mean ± SD peak expiratory flow increased to 44 ± 7 L/min compared with 31 ± 7 L/min without treatment (P < .001). Manual rib cage compression combined with endotracheal suctioning increased mucus clearance compared with closed suctioning alone (mucus amounts, 5.5 [3.4-9.4] g vs 0.7 [0.5-2.0] g; P = .004); however, it did not improve gas exchange and radiologic findings. There were no significant differences in hemodynamic variables between the 2 groups. Our findings indicated that hard and brief manual rib cage compression combined with closed suctioning was safe and led to improvement of mucus clearance; however, no effectiveness was confirmed with regard to oxygenation and ventilation.

Effect of laparotomy on respiratory muscle activation pattern.

Muscular tone of the abdominal wall is important in maintaining transdiaphragmatic pressures and its loss can lead to decreased lung volumes. Patients who are status postlaparotomy are at risk of developing atelectasis. The compensatory role of respiratory muscle activity in postlaparotomy is not well studied. Normally, inspiratory muscles are active during inspiration and passive during expiration to allow for lung recoil. However, electrical activities of the inspiratory muscles continue during early expiratory phase to prevent rapid loss of lung volume. This activity is known as post-inspiratory inspiratory activity (PIIA). In this study, we hypothesized that laparotomy will elicit an increase in PIIA, which is enhanced by respiratory chemical loading. Experiments were conducted in cats under three different conditions: intact abdomen (n=3), open abdomen (n=10), and post abdominal closure (n=10) during eupnea and hypercapnia (10% CO2). Electromyography (EMG) activities of the diaphragm and parasternal muscles were recorded and peak EMG amplitude, PIIA time, and area under the curve were measured. Intraesophageal pressure was also obtained. PIIA was significantly higher under open abdominal conditions in comparison to intact abdomen during eupnea. Our data indicates that PIIA is increased during open abdomen and may be an important compensatory mechanism for altered respiratory mechanics induced by laparotomy. Also, PIIA remained elevated after abdominal closure. However, under hypercapnia, PIIA was significantly higher during intact abdomen in comparison to open abdomen, which is thought to be due to respiratory muscle compensation under chemical loading.

1-A-F-4. Respiratory fluctuation of pain related brain potential: Comparison of hand and foot stimulation

To study the effects of respiration on intraepidermal electrical stimulus-evoked potentials (IESEPs), sympathetic activities and pain sensations, we recorded electroencephalogram (EEG), sympathetic skin response (SSR), digital plethysmogram, subjective pain rating scale and exhaled CO2 in 8 healthy volunteers. The electrical stimulation to the epidermis of the dorsum of the left hand or foot was applied once or twice a minute when an exhaled CO2 level abruptly exceeded 20 mmHg (early expiratory phase, EP) or when it fell bellow 20 mmHg (early inspiratory phase, IP). The stimulus intensity was set at the threshold or 4 times the threshold, and unchanged during the experiment. Subjective pain rating scales fluctuated between “No hurt” and “Hurts a little bit” with an intensity of the threshold or between “Hurts a little bit” and “Hurts a little more” with an intensity of 4 times the threshold; but the former was more frequent for EP stimulation in both stimulus sites. The mean amplitudes of P400 in IESEPs and SSR were smaller for EP stimulation than IP stimulation in both stimulus sites. Our findings suggest that pain information processing fluctuates during respiration, and that pain may be partially gated in the expiratory phase in either stimulus site.

O3-D-10. Epidermal electrical stimulation-induced brain potential and sympathetic activity are diminished during expiration

To investigate the effects of respiration on pain sensations and brain or autonomic responses, we recorded EEG, sympathetic skin response (SSR), digital plethysmogram (DPG), subjective pain rating scale and exhaled CO 2 in 10 healthy volunteers. Electrical stimulation to the epidermis of the dorsum of the left hand was applied once or twice a minute when an exhaled CO 2 level exceeded 20 mmHg (early expiratory phase, EP) or when it fell below 20 mmHg (early inspiratory phase, IP). The stimulus intensity was set at the threshold of pain or 4 times the threshold in each subject. Despite constant stimulus intensity, subjective pain rating scales fluctuated between EP and IP. In either stimulus intensity, EP stimulation produced weaker pain feeling compared to IP stimulation. The mean amplitudes of N1/P1 in the pain-related potentials and SSR were smaller at EP stimulation than IP stimulation. The DPG wave in synchronization with a heartbeat gradually decreased after EP or IP stimulation and showed a trough on the 6th or 7th beat post-stimulus; but a decrease in DPG wave was less evident at EP stimulation. Our findings suggest that pain information processing fluctuates during respiration and that pain may be gated in the expiratory phase.

Effects of Manual Rib Cage Compressions on Expiratory Flow and Mucus Clearance During Mechanical Ventilation*

We investigated the effects of two different types of manual rib cage compression on expiratory flow and mucus clearance during prolonged mechanical ventilation in pigs. Prospective randomized animal study. Animal research facility, University of Barcelona, Spain. Nine healthy pigs. Pigs were tracheally intubated, sedated, paralyzed, and mechanically ventilated. The animals were prone on a surgical bed in the anti-Trendelenburg position. The experiments were carried out at approximately 60 and 80 hrs from the beginning of mechanical ventilation. Two types of manual rib cage compressions were tested: Hard and brief rib cage compressions synchronized with early expiratory phase (hard manual rib cage compression) and soft and gradual rib cage compressions applied during the late expiratory phase (soft manual rib cage compression). The interventions were randomly applied for 15min with a 15-min interval between treatments. Respiratory flow and mucus movement were assessed during the interventions. Respiratory mechanics and hemodynamics were assessed prior to and after the interventions. Peak expiratory flow increased to 60.1±7.1L/min in comparison to 51.2±4.6L/min without treatment (p < 0.0015) and 48.7±4.3L/min with soft manual rib cage compression (p = 0.0002). Similarly, mean expiratory flow increased to 28.4±5.2L/min during hard manual rib cage compression vs. 15.9±2.2 and 16.6±2.8L/min without treatment and soft manual rib cage compression, respectively (p = 0.0006). During hard manual rib cage compression, mucus moved toward the glottis (1.01 ± 2.37mm/min); conversely, mucus moved toward the lungs during no treatment and soft manual rib cage compression, -0.28 ± 0.61 and -0.15±0.95mm/min, respectively (p = 0.0283). Soft manual rib cage compression slightly worsened static lung elastance and cardiac output (p = 0.0391). Hard manual rib cage compression improved mucus clearance in animals positioned in the anti-Trendelenburg position. The technique appeared to be safe. Conversely, soft manual rib cage compression was not effective and potentially unsafe. These findings corroborate the predominant role of peak expiratory flow on mucus clearance.

Modulation of respiratory sinus arrhythmia in rats with central pattern generator hardware

We report on the modulation of respiratory sinus arrhythmia in rats with central pattern generator (CPG) hardware made of silicon neurons. The neurons are made to compete through mutually inhibitory synapses to provide timed electrical oscillations that stimulate the peripheral end of vagus nerve at specific points of the respiratory cycle: the inspiratory phase (φ1), the early expiratory phase (φ2) and the late expiratory phase (φ3). In this way the CPG hardware mimics the neuron populations in the brainstem which through connections with cardiac vagal motoneurones control respiratory sinus arrhythmia (RSA). Here, we time the output of the CPG hardware from the phrenic nerve activity recorded from rats while monitoring heart rate changes evoked by vagal nerve stimulation (derived from ECG) controlled by the CPG. This neuroelectric stimulation has the effect of reducing the heart rate and increasing the arterial pressure. The artificially induced RSA strongly depends on the timing of pulses within the breathing cycle. It is strongest when the vagus nerve is stimulated during the inspiratory phase (φ1) or the early expiratory phase (φ2) in which case the heart rate slows by 50% of the normal rate. Heart rate modulation is less when the same exact stimulus is applied during the late expiratory phase (φ3). These trials show that neurostimulation by CPG hardware can augment respiratory sinus arrhythmia. The CPG hardware technology opens a new line of therapeutic possibilities for prosthetic devices that restore RSA in patients where respiratory-cardiac coupling has been lost.

A 72-hour study to test the efficacy and safety of the “Mucus Slurper” in mechanically ventilated sheep

In patients intubated with endotracheal tubes (ETTs), suctioning is routinely performed to remove mucus from within the ETT and trachea. The Mucus Slurper is a novel ETT with built-in suction ports arranged radially at its tip. We evaluated the safety and efficacy of the Mucus Slurper, compared with conventional tracheal suction, to prevent airway obstruction in sheep with the ETT and trachea oriented below horizontal. Prospective randomized animal study. Animal research facility at the National Institutes of Health. Twelve healthy sheep. Sheep were randomized to be intubated with either the Mucus Slurper (study group) or a Hi-Lo Tracheal Tube (Mallinckrodt, St. Louis, MO) (control group) and mechanically ventilated for 72 hrs. In the study group, automatic, timed tracheal aspiration lasted 0.3 secs, was repeated every 2 mins, and was synchronized with the early expiratory phase. In the control group, tracheal suction was performed every 6 hrs or as required. In the control group, tracheal secretions accumulated progressively within the ETT and the trachea. In the study group, all mucus that reached the tip of the Mucus Slurper was aspirated, keeping the lumen of the ETT, and proximal trachea, free from secretions. In the study group, expiratory water trap protein concentration, a crude index to measure mucus drainage through the ETT, was consistently less than the control group (p < .001). At autopsy, no macroscopic injury to the tracheal mucosa was found in either group. In the study group, the respiratory circuit was less colonized than in the control group. There were no statistically significant differences between the two groups in bacterial colonization of the lungs/bronchi. The Mucus Slurper, combined with orientation of the trachea below horizontal, prevents accumulation of secretions within the lumen of the ETT and trachea, without need for conventional tracheal suctioning.

The characteristics of the spectra of superior venae cavae in patients with right heart failure

BackgroundAimed to elucidate the characteristics of the spectra of superior venae cavae (SVC) in respiratory cycles in patients with right heart failure.MethodsThe spectra of SVC of 30 patients with right heart failure and 30 paired healthy subjects were recorded through right supraclavicular fossa view. The profiles of spectra of superior venae cavae were observed, and peak velocity and velocity time integral (VTI) of every wave of SVC under spontaneous respiration were measured for statistical analysis.ResultsIn healthy subjects, the peak velocities and VTI of S wave and D wave increased in inspiratory phase and diminished in expiratory phase, and which of S wave were larger than which of D wave in whole respiratory cycle. In patients with right heart failure, spectral variations of SVC could be classified into three patterns: Pattern I: peak velocities and VTI of S wave were larger than that of D wave in early inspiratory phase, but peak velocities and VTI of D wave were larger than those of S wave in late inspiratory phase and early expiratory phase [Pattern I-1], even in whole respiratory cycle [Pattern I-2]; Pattern II: the S wave disappeared and was substituted by inverse wave with low amplitude in whole respiratory cycle. Pattern III: the profiles of the spectra of SVC in patients were similar to those of healthy subjects. In the whole, the respiratory variation ratios of peak velocities and VTI of S wave and D wave were diminished in patients compared with those in healthy subjects.ConclusionThe spectra of superior venae cavae in patients with right heart failure were abnormal, and these characteristics could be used as signs in evaluating right heart failure.

Highly H+-sensitive neurons in the caudal ventrolateral medulla of the rat.

The ventral surface of the caudal ventrolateral medulla (cVLM) has been shown to generate intense respiratory responses after surface acid-base stimulation. With respect to their chemosensitive characteristics, cVLM neurons have been less studied than other rostral-most regions of the brainstem. The purpose of these experiments was to determine the bioelectric responses of cVLM neurons to acidic stimuli and to determine their chemosensitive properties. Using extracellular and microiontophoretic techniques, we recorded electrical activities from 117 neurons in an area close to the ventral surface of the cVLM in anaesthetised rats. All neurons were tested for their sensitivity to H+. The fluorescent probe BCECF was used to measure extracellular pH changes produced by the microiontophoretic injection of H+ in brainstem slices. This procedure provided an estimation of the local changes in pH produced by microiontophoretic H+ application in the anaesthetised rat. Neurons coupled to the respiratory cycle, R (n = 51), were not responsive to direct stimulation with H+. Sixty-six neurons that did respond to H+ stimulation were uncoupled from respiration, and identified as NR neurons. These neurons presented distinct ranges of H+ sensitivity. The neuronal sensitivity to H+ was mainly assessed by the slope of the stimulus-response curve, where the steeper the slope, the higher the H+ sensitivity. On this basis, NR neurons were classed as being either weakly or highly sensitive to H+. NR neurons with a high H+ sensitivity (n = 12) showed an average value of 34.17 +/- 7.44 spikes s-1 (100 nC)-1 (mean +/- S.D.) for maximal slope and an EC50 of 126.76 +/- 33 nC. Suprathreshold H+ stimulation of highly sensitive NR neurons elicited bursting pattern responses coupled to the respiratory cycle. The bursting responses, which were synchronised with the inspiratory phase and the early expiratory phase of the respiratory cycle, lasted for several seconds before returning to the steady state firing pattern characteristic of the pre-stimulus condition. These NR neurons, which possess the capacity to detect distinct H+ concentrations in the extracellular microenvironment, are excellent candidates to serve in a chemoreceptor capacity in the caudal medulla.

Role of nucleus parabrachialis complex in inspiratory off-switch studied in isolated brainstem-spinal cord preparation from neonatal rat

The nucleus parabrachialis complex (NPB) of the pons is known as a respiratory modulating center. The NPB and the medullary respiratory center are mutually interconnected and vagus nerve afferents from pulmonary stretch receptors project to the NPB [1]. There is much evidence in in vivo preparations from adult mammals [2] that the NPB plays a crucial in the inspiratory off-switch. In the present study, we examined how the NPB participates in the inspiratory off-switch using brainstem-spinal cord preparations obtained from 0–4 days old rats. We hemi-sectioned the pons keeping one side intact. First, we examined the effects of NPB electrical stimulation on C4 ventral nerve inspiratory activity. The electrical stimulation (0.1 ms duration, 1–5 trains, 20 ms interval) applied at various times (100–300 ms after the onset of C4 inspiratory activity) induced a transient depression or termination in C4 inspiratory activity. This depression was stronger when the stimulation was applied near the end of inspiratory activity but less conspicuous when it was applied at around the peak of inspiratory activity. Thus, activation of the NPB neuronal elements could produce termination of inspiratory activity in this in vitro preparation similar to the in vivo preparation. Previous in vivo experiments in adult mammals suggested that an NMDA receptor- mediated off-switch mechanism is present in the inspiratory termination [3]. Then, we examined whether a similar mechanism is involved in the above-observed inspiratory off-switch in the in vitro preparation. It was shown that the inhibition of C4 inspiratory activity induced by the NPB stimulation was greatly reduced by perfusion of NMDA antagonists (MK-801, APV) and that the inhibition was blocked by perfusion of a GABAA-antagonist (Bicuculline). To determine the location of NMDA receptors responsible for this inhibition by the NPB stimulation, an NMDA-antagonist MK-801 (1 mM) was microinjected into the NPB using a glass capillary placed in the vicinity of the stimulation electrode. The injection of MK-801 reduced the inhibition of C4 inspiratory activity by the NPB stimulation, indicating that NMDA receptor-mediated processes take place within the NPB. Since neurons and/or neuron networks responsible for inspiratory off-switch are expected to exist in the NPB, we tried to find respiratory neurons and analyzed their distribution and firing patterns. Neurons were recorded from the cut-surface of the intact half of the pons using whole cell patch clamp method. We found several types of respiratory neurons: inspiratory, tonic inspiratory, expiratory and inspiratory-expiratory (I-E) neurons. The population of I-E neurons was the largest, being more than 50% of the recorded neurons. I-E neurons fired from middle of C4 inspiratory activity through the early expiratory phase and were inhibited at the early part of C4 inspiratory activity. Perfusion of MK-801 (10 M) decreased significantly the driving potential and burst duration of I-E neurons. In addition, this perfusion decreased also the amplitudes of EPSPs induced by vagal nerve stimulation in the I-E neurons. In conclusion, 1) the NPB is involved in the inspiratory off-switch in in vitro preparations, 2) NMDA receptors within the NPB mediate, at least partly, the NPB-related inspiratory off-switch, and 3) a relatively large population of I-E neurons of the NPB could be responsible for the NPB-related inspiratory termination.

Augmentation of muscle nociceptive respiratory reflex facilitation by vagal afferents.

Vagal influence on the facilitation of phrenic neural activity during respiratory phase-locked, gastrocnemius muscle nerve nociceptive electrical stimulation was examined in anesthetized, glomectomized, paralyzed, and artificially ventilated cats. (1) In the vagi-intact state, respiratory reflex facilitation was characterized by a sharp rise in peak amplitude, maximum rate of rise or slope, and mean rate of rise of integrated phrenic nerve activity. This was greater during inspiratory phase-locked (T1-locked) muscle nerve electrical stimulation than during expiratory phase-locked (TE-locked) muscle nerve electrical stimulation. "Evoked post-inspiratory phrenic activity" during the early expiratory phase was also observed during TE-locked muscle nerve electrical stimulation. (2) Bilateral vagotomy significantly attenuated the respiratory facilitation during both T1- and TE-locked muscle nerve electrical stimulation. In particular, the "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation was also attenuated or almost completely abolished. (3) Conditioning electrical stimulation of the vagus nerve revealed facilitatory reflexes which co-exist with inspiratory inhibitory reflexes. (4) The "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation, which was attenuated or abolished after vagotomy, was restored after vagal T1-locked conditioning stimuli combined with TE-locked muscle nerve electrical stimulation. The results suggest that vagal facilitatory reflexes augment the respiratory reflex facilitation during muscle nociceptive stimulation.

Classification of giant bullae and changes in pulmonary function after bullectomy based on analysis of diaphragm-bulla motion

This study presents a classification of giant bullae based on analysis of the effects of giant bullae on adjacent lung tissues and changes in pulmonary function after bullectomy. The diaphragm-bulla motion and their relationship during breathing in the supine position were evaluated by analysis of serial posteroanterior chest X-rays in 9 patients with giant bullae whose diaphragm-rib cage motion were synchronous. We measured craniocaudal displacement of the diaphragm and bullae.Patients were divided into three groups according to diaphragm bulla motion. First, three patients whose diaphragm bulla motion had no phase shift had normal values in spirometric pulmonary function test before bullectomy, and showed decrease in %VC (p 0.05), FEV1.0, MVV%pred. and increase in RV/TLC after bullectomy. These impaired values returned to almost the same level one year after the operation. Second, three patients whose bullae inflated in the early expiratory phase and compressed adjacent lung tissues showed no changes on tests except a decrease in RV/TLC one year after the operation. Third, three patients whose bullae inflated at the end of the expiratory phase or kept their size during respiration showed improvement in FEV1.0 and MVV%pred. from early postoperative course and%VC also increased.We conclude that the classification of giant bulla according to the diaphragm-bulla motion can provide useful information for evaluating the pathophysiology of giant bullae and predicting of pulmonary function after bullectomy.

Activity of bulbar respiratory neurons during passive hyperventilation

Discharge of bulbar respiratory neurons was recorded extracellularly with tungsten microelectrodes in pentobarbitalized, in urethanized, and in unanesthetized decerebrate cats. Neuronal discharges were followed while the animals were hyperventilated to apnea. Most inspiratory neurons were inactivated, with late neurons first affected. Some early units continued to exhibit a respiratory rhythm for a few seconds after apnea was induced. An estimated quarter of all inspiratory neurons went progressively into tonic discharge which could not be arrested by further overventilation. The majority of expiratory neurons was sent into slow tonic discharge could not be arrested by additional overventilation. Prior to hyperventilation, most of these neurons began firing in the early expiratory phase. The remaining expiratory neurons, predominantly late units, were progressively inactivated by hyperventilation. Results suggest that in this type of apnea the residual tonic discharge exists simultaneously in inspiratory and expiratory neuron populations. In recovery from apnea, some members of both inspiratory and expiratory neuron populations began to discharge rhythmically a few cycles before any discernible inspiration.