Respiratory load compensation in chronic airway obstruction

To assess respiratory neuromuscular function and load compensating ability in patients with chronic airway obstruction (CAO), we studied eight stable patients with irreversible airway obstruction during hyperoxic CO2 rebreathing with and without a 17 cmH2O X l-1 X s flow-resistive inspiratory load (IRL). Minute ventilation (VE), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi) were monitored. Pdi and EMGdi were obtained via a single gastroesophageal catheter with EMGdi being quantitated as the average rate of rise of inspiratory (moving average) activity. Based on the effects of IRL on the Pdi response to CO2 [delta Pdi/delta arterial CO2 tension (PaCO2)] and the change in Pdi for a given change in EMGdi (delta Pdi/delta EMGdi) during rebreathing, two groups could be clearly identified. Four patients (group A) were able to increase delta Pdi/delta PaCO2 and delta Pdi/delta EMGdi, whereas in the other four (group B) the IRL responses decreased. All group B patients were hyperinflated having significantly greater functional residual capacity (FRC) and residual volume than group A. In addition the IRL induced percent change in delta Pdi/delta PaCO2, and delta VE/delta PaCO2 was negatively correlated with lung volume so that in the hyperinflated group B the higher the FRC the greater was the decrease in Pdi response due to IRL. In both groups the greater the FRC the greater was the decrease in the ventilatory response to loading. Patients with CAO, even with severe airways obstruction, can effect load compensation by increasing diaphragmatic force output, but the presence of increased lung volume with the associated shortened diaphragm prevents such load compensation.     

Effects of inspiratory resistive load on respiratory control in hypercapnia and exercise

Eight healthy young men underwent two separate steady-state incremental exercise runs within the aerobic range on a treadmill with alternating periods of breathing with no load (NL) and with an inspiratory resistive load (IRL) of approximately 12 cmH2O.1-1.s. End-tidal PCO2 was maintained constant throughout each run at the eucapnic or a constant hypercapnic level by adding 0-5% CO2 to the inspired O2. Hypercapnia caused a steepening, as well as upward shift, relative to the corresponding eucapnic ventilation-CO2 output (VE - VCO2) relationship in NL and IRL. Compared with NL, the VE - VCO2 slope was depressed by IRL, more so in hypercapnic [-19.0 +/- 3.4 (SE) %] than in eucapnic exercise (-6.0 +/- 2.0%), despite a similar increase in the slope of the occlusion pressure at 100 ms - VCO2 (P100 - VCO2) relationship under both conditions. The steady-state hypercapnic ventilatory response at rest was markedly depressed by IRL (-22.6 +/- 7.5%), with little increase in P100 response. For a given inspiratory load, breathing pattern responses to separate or combined hypercapnia and exercise were similar. During IRL, VE was achieved by a greater tidal volume (VT) and inspiratory duty cycle (TI/TT) along with a lower mean inspiratory flow (VT/TI). The increase in TI/TT was solely because of a prolongation of inspiratory time (TI) with little change in expiratory duration for any given VT. The ventilatory and breathing pattern responses to IRL during CO2 inhalation and exercise are in favor of conservation of respiratory work.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effort sensation, chemoresponsiveness, and breathing pattern during inspiratory resistive loading.

Although inspiratory resistive loading (IRL) reduces the ventilatory response to CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are few data about the converse situation: whether CO2 responsiveness influences sustained load compensation and whether awareness of respiratory effort modifies this behavior. We studied 12 normal men during CO2 rebreathing while free breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2, IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2 was inversely related to an index of effort perception (IES/VE; r = -0.63, P less than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05) and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that in normal subjects perception of inspiratory effort can modify free-breathing CO2 responsiveness and is as important as CO2 sensitivity in determining the response to short-term resistive loading. Individuals with good perception choose a small-tidal volume and short-TI breathing pattern during loading, possibly to minimize the discomfort of breathing.     

Effects of changes in CO2 partial pressure on the sensation of respiratory drive

The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55-60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded.     

Respiratory responses to ventilatory loading following low cervical spinal cord injury

This study compared the respiratory responses to ventilatory loading in 8 normal subjects and 11 quadriplegic patients with low cervical spinal cord transection. Progressive hypercapnia was produced by rebreathing. Rebreathing trials were carried out with no added load and with inspiratory resistive loads of 5 and 16 cmH2O. l-1 X s. Measurements were made of ventilation and of diaphragmatic electromyographic activity. Base-line hypercapnic ventilatory responses were significantly lower than normal in the quadriplegic patients, but the effects of resistive loading on the ventilatory responses were comparable in the two groups. The change in peak moving-average diaphragmatic electrical activity (DI peak) for a given change in CO2 partial pressure (PCO2) and DI peak at PCO2 55 Torr increased significantly with resistive loading both in the normal subjects and the quadriplegic patients. In the normal subjects, but not in the quadriplegic patients, inspiratory duration increased progressively with increasing resistance. The increase in DI peak during ventilatory loading in the normal subjects was a consequence of inspiratory prolongation. In contrast, in the quadriplegic patients during breathing against the larger resistive load, there was a significant increase in the average rate of rise (DI peak divided by the time from onset to peak) of diaphragmatic activity. The change in DI rate of rise for a given change in PCO2 increased to 137 +/- 13% (SE), and the DI rate of rise at PCO2 55 Torr increased to 128 +/- 8% (SE) of control values. These results indicate that compensatory increases in diaphragmatic activation during ventilatory loading occur in quadriplegic patients in whom afferent feedback from rib cage receptors is disrupted.     

Effect of diaphragm fatigue on neural respiratory drive.

To test the hypothesis that diaphragm fatigue leads to an increase in neural respiratory drive, we measured the esophageal diaphragm electromyogram (EMG) during CO(2) rebreathing before and after diaphragm fatigue in six normal subjects. The electrode catheter was positioned on the basis of the amplitude and polarity of the diaphragm compound muscle action potential recorded simultaneously from four pairs of electrodes during bilateral anterior magnetic phrenic nerve stimulation (BAMPS) at functional residual capacity. Two minutes of maximum isocapnic voluntary ventilation (MIVV) were performed in six subjects to induce diaphragm fatigue. A maximal voluntary breathing against an inspiratory resistive loading (IRL) was also performed in four subjects. The reduction of transdiaphragmatic pressure elicited by BAMPS was 22% (range 13-27%) after 2 min of MIVV and was similar, 20% (range 13-26%), after IRL. There was a linear relationship between minute ventilation (VE) and the root mean square (RMS) of the EMG during CO(2) rebreathing before and after fatigue. The mean slope of the linear regression of RMS on VE was similar before and after diaphragm fatigue: 2.80 +/- 1.31 vs. 3.29 +/- 1.40 for MIVV and 1.51 +/- 0.31 vs 1.55 +/- 0.31 for IRL, respectively. We conclude that the esophageal diaphragm EMG can be used to assess neural drive and that diaphragm fatigue of the intensity observed in this study does not affect respiratory drive.     

Vagal contributions to respiratory muscle activity during eupnea in the awake dog.

We examined the effects of reversible vagal cooling on respiratory muscle activities in awake chronically instrumented tracheotomized dogs. We specifically analyzed electromyographic (EMG) activity and its ventilatory correlates, end-expiratory lung volume (EELV) and diaphragmatic resting length via sonomicrometry. Elimination of phasic and tonic mechanoreceptor activity by vagal cooling doubled the EMG activity of the costal, crural, and parasternal muscles, with activation occurring sooner relative to the onset of inspiratory flow. Diaphragmatic postinspiration inspiratory activity in the intact dog coincided with a brief mechanical shortening of the diaphragm during early expiration; vagal blockade removed both the electrical activity and the mechanical shortening. Vagal blockade also doubled the EMG activity of a rib cage expiratory muscle, the triangularis sterni, but reduced that of an abdominal expiratory muscle, the transversus abdominis. Within-breath electrical activity of both muscles occurred sooner relative to the onset of expiratory flow during vagal blockade. Vagal cooling was also associated with a 12% increase in EELV and a 5% decrease in end-expiratory resting length of the diaphragm. We conclude that vagal input significantly modulates inspiratory and expiratory muscle activities, which help regulate EELV efficiently and optimize diaphragmatic length during eupneic breathing in the awake dog.     

Respiratory muscle function during CO2 rebreathing with inspiratory flow-resistive loading

We investigated the respiratory muscle contribution to inspiratory load compensation by measuring diaphragmatic and intercostal electromyograms (EMGdi and EMGic), transdiaphragmatic pressure (Pdi), and thoracoabdominal motion during CO2 rebreathing with and without 15 cmH2O X l-1 X s inspiratory flow resistance (IRL) in normal sitting volunteers. During IRL compared with control, Pdi measured during airflow and during airway occlusion increased for a given change in CO2 partial pressure and EMGdi, and there was a greater decrease in abdominal (AB) end expiratory anteroposterior dimensions with increased expiratory gastric pressure (Pga), this leading to an inspiratory decline in Pga with outward AB movement, indicating a passive component to the descent of the abdomen-diaphragm. The response of EMGic to IRL was similar to that of EMGdi, though rib cage (RC)-Pga plots did infer intercostal muscle contribution. We conclude that during CO2 rebreathing with IRL there is improved diaphragmatic neuromuscular coupling, the prolongation of inspiration promoting a force-velocity advantage, and increased AB action serving to optimize diaphragm length and configuration, as well as to provide its own passive inspiratory action. Intercostal action provides increased assistance also. Therefore, compensation for inspiratory resistive loads results from the combined and integrated effort of all respiratory muscle groups.     

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.     

Expiratory abdominal muscle activity during ventilatory chemostimulation in piglets

We examined abdominal muscle minute electromyographic (EMG) activity (peak moving time average EMG x respiratory rate) during eupnea, hyperoxic hypercapnia (8% CO2-40% O2-balance N2), and hypoxia (13% O2) in 12 anesthetized (0.5% halothane) newborn piglets. In addition, we assessed the role of vagal afferent pathways in the abdominal muscles' response to ventilatory chemostimulation by examining abdominal EMG activity (EMGab) before and after bilateral cervical vagotomy in five animals. Phasic expiratory EMGab was observed in 11 of 12 piglets during eupnea. Hypercapnia was associated with a sustained augmentation of minute EMGab (444 +/- 208% control). In contrast, hypoxia consistently augmented (1 min, 193 +/- 33% control) then diminished (5 min, 126 +/- 39% control) minute EMGab. Vagotomy resulted in a decline in peak moving time average EMGab by approximately one-half (48 +/- 18% control); the abdominal muscles' response to ventilatory chemostimulation, however, was qualitatively unchanged. We conclude that 1) expiration during eupnea in anesthetized newborn piglets is associated with phasic EMGab; 2) both hypercapnia and hypoxia augment minute EMGab; however, only hypercapnia is associated with sustained augmentation; and 3) although vagal afferents have a role in modulating the base-line level of EMGab, other extravagal mechanisms appear to determine the pattern of EMGab in response to ventilatory chemostimulation.     

Influence of upper airway sensory receptors on respiratory muscle activation in humans

We reasoned that neural information from upper airway (UA) sensory receptors could influence the relationship between UA and diaphragmatic neuromuscular responses to hypercapnia. In this study, the electromyographic (EMG) activities of the alae nasi (AN), genioglossus (GG), and chest wall (CW) or diaphragm (Di) to ventilatory loading were assessed in six laryngectomized, tracheostomized human subjects and in six subjects breathing with an intact UA before and after topical UA anesthesia. The EMG activities of the UA and thoracic muscles increased at similar rates with increasing hypercapnia in normal subjects, in subjects whose upper airways were anesthetized, and in laryngectomized subjects breathing with a cervical tracheostomy. Furthermore, in the laryngectomized subjects, respiratory muscle EMG activation increased with resistive inspiratory loading (15 cmH2O X l-1 X s) applied at the level of a cervical tracheostomy. At an average expired CO2 fraction of 7.0%, resistive loading resulted in a 93 +/- 26.3% (SE) increase in peak AN EMG activity, a 39 +/- 2.0% increase in peak GG EMG activity, and a 43.2 +/- 16.5% increase in peak CW (Di) EMG activity compared with control values. We conclude that the ventilatory responses of the UA and thoracic muscles to ventilatory loading are not substantially influenced by laryngectomy or UA anesthesia.     

Interactions between lung stretch and PaCO2 in modulating ventilatory activity in dogs

The effects of changes in airway pressure (Paw) and arterial PCO2 (PaCO2) on ventilatory activity were studied in anesthetized thoracotomized dogs in which both lungs were ventilated separately. Pulmonary artery occlusion on one side and contralateral vagotomy allowed the reflex effects on ventilation of changes in Paw and PaCO2 to be elicited independently of each other. Ventilatory activity was assessed from integrated efferent phrenic activity, analyzed with respect to burst amplitude (Phr), burst frequency (f), and inspiratory TI) and expiratory duration (TE). While Phr increased linearly with PaCO2, it was independent of Paw. Both PaCO2 and Paw affected f in a complex nonadditive way; this response was entirely mediated by effects on TE, TI being unaffected by either stimulus. The analog of ventilation, estimated as Phr x f, increased linearly with PaCO2 and decreased linearly with Paw, but the effects of both stimuli appeared to be additive. It is concluded that the apparently simple effect of Paw and PaCO2 on ventilation results from more complex effects these stimuli exert on its components.     

Cardiorespiratory failure in rat induced by severe inspiratory resistive loading.

The mechanisms underlying acute respiratory failure induced by respiratory loads are unclear. We hypothesized that, in contrast to a moderate inspiratory resistive load, a severe one would elicit central respiratory failure (decreased respiratory drive) before diaphragmatic injury and fatigue. We also wished to elucidate the factors that predict endurance time and peak tracheal pressure generation. Anesthetized rats breathed air against a severe load ( approximately 75% of the peak tracheal pressure generated during a 30-s occlusion) until pump failure (fall in tracheal pressure to half; mean 38 min). Hypercapnia and hypoxemia developed rapidly ( approximately 4 min), coincident with diaphragmatic fatigue (decreased ratio of transdiaphragmatic pressure to peak integrated phrenic activity) and the detection in blood of the fast isoform of skeletal troponin I (muscle injury). At approximately 23 min, respiratory frequency and then blood pressure fell, followed immediately by secondary diaphragmatic fatigue. Blood taken after termination of loading contained cardiac troponin T (myocardial injury). Contrary to our hypothesis, diaphragmatic fatigue and injury occurred early in loading before central failure, evident only as a change in the timing but not the drive component of the central respiratory pattern generator. Stepwise multiple regression analysis selected changes in mean arterial pressure and arterial Pco(2) during loading as the principal contributing factors in load endurance time, and changes in mean arterial pressure as the principal contributing factor in peak tracheal pressure generation. In conclusion, the temporal development of respiratory failure is not stereotyped but depends on load magnitude; moreover respiratory loads induce cardiorespiratory, not just respiratory, failure.     

Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.     

Respiratory timing during NREM sleep in patients with occlusive sleep apnea

To study respiratory timing mechanisms in patients with occlusive apnea, inspiratory and expiratory times (TI and TE) were calculated from the diaphragmatic electromyogram obtained in seven patients during non-rapid-eye-movement (NREM) sleep. Peak diaphragmatic activity (EMGdi) had a curvilinear relationship with TI during the ventilatory and occlusive phases such that TI shortened as EMGdi decreased during the ventilatory phase (r = 0.87, P less than 0.05) and it prolonged as EMGdi increased during the occlusive phase (r = 0.89, P less than 0.02). However, EMGdi vs. TI for the occlusive phase was shifted to the right of that for the ventilatory phase, reflecting the relatively longer TI during upper airway occlusion. TI also had a linear relationship with pleural pressure (r = 0.94, P less than 0.001) that remained unchanged during the ventilatory and occlusive phases such that it prolonged as negative inspiratory pressure increased. These results indicate that respiratory timing is continuously modified in patients with occlusive apnea as inspiratory neural drive fluctuates during NREM sleep and suggest that this modification is due to the net effects of changing inspiratory neural drive and afferent input predominantly from upper airway mechanoreceptors.     

Effect of posture on inspiratory muscle electromyogram response to hypercapnia

The aim of our study was to examine the effect of posture on inspiratory muscle activity response to hypercapnia. Recent research has revealed that in normal subjects the activation of the rib cage muscles and of the diaphragm is actually greater in the upright than in the supine position during resting tidal breathing. In this study we examined whether the upright position necessarily entails a greater activation of the inspiratory muscles also under conditions of ventilatory stress. For this purpose we compared the responses to CO2-rebreathing in the supine and sitting positions in five volunteers, by simultaneously recording the electromyogram of the diaphragm (EMGdi) and the intercostal muscles (EMGint). The electromyogram was recorded by means of surface electrodes to measure the EMG amplitude. While the slopes of ventilatory (VE) response to increasing arterial CO2 tension (PaCO2) were similar in the two positions, both the EMGdi-VE and EMGint-VE relationship showed steeper slopes in the supine than in the sitting position. In each CO2 run the increases in EMGdi were linearly related to those in EMGint. This relationship was not affected by the body position. These results suggested that, in spite of similar ventilatory responses to CO2-rebreathing in the lying and sitting positions, the supine position, in humans, required a higher activation of the inspiratory muscles.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Alterations in respiratory muscle activation in the ischemic fatigued canine diaphragm

The purpose of the present study was to examine the respiratory motor response to diaphragm fatigue. Studies were performed using in situ diaphragm muscle strips dissected from the left costal diaphragm in anesthetized dogs. The left inferior phrenic artery was isolated, and diaphragmatic strip fatigue was elicited by occluding this vessel. Strip tension, strip electromyographic activity, parasternal electromyographic activity, and the electromyogram of the right hemidiaphragm were recorded during spontaneous breathing efforts before, during, and after periods of phrenic arterial occlusion. In separate trials, we examined the neuromuscular responses to phrenic arterial occlusion at arterial PCO2 (PaCO2) of 40, 55, and 75 Torr. No fatigue and no alteration in electromyographic activities were observed in trials at PaCO2 of 40 Torr. During trials at PaCO2 of 55 and 75 Torr, however, diaphragm tension fell, the peak height of the diaphragm strip electromyogram decreased, and the peak heights of the parasternal and right hemidiaphragm electromyograms increased. Relief of phrenic arterial occlusion resulted in a return of strip tension and all electromyograms toward base-line values. In additional experiments, the left phrenic nerve was sectioned in the chest after producing fatigue. Phrenic section was followed by an increase in the peak height of the left phrenic neurogram (recorded above the site of section). This latter finding suggests that diaphragm strip motor drive may be reflexly inhibited during the development of fatigue by neural traffic carried along phrenic afferents.     

Volume-timing relationships during cough and resistive loading in the cat.

The relationship between pulmonary volume-related feedback and inspiratory (CTI) and expiratory (CTE) phase durations during cough was determined. Cough was produced in anesthetized cats by mechanical stimulation of the intrathoracic tracheal lumen. During eupnea, the animals were exposed to single-breath inspiratory and expiratory resistive loads. Cough was associated with large increases in inspiratory volume (VI) and expiratory volume (VE) but no change in phase durations compared with eupnea. There was no relationship between VI and CTI during coughing. A linear relationship with a negative slope existed between VI and eupneic inspiratory time during control and inspiratory resistive loading trials. There was no relationship between VE and CTE during all coughs. However, when the first cough in a series or a single cough was analyzed, the VE/CTE relationship had a positive slope. A linear relationship with a negative slope existed between VE and eupneic expiratory time during control and expiratory resistive loading trials. These results support separate ventilatory pattern regulation during cough that does not include modulation of phase durations by pulmonary volume-related feedback.     

Interaction of hypoxic and hypercapnic stimuli on breathing pattern in the newborn rat

We aimed to investigate whether newborn rats respond to acute hypoxia with a biphasic pattern as other newborn species, the characteristics of their ventilatory response to hypercapnia, and the ventilatory response to combined hypoxic and hypercapnic stimuli. First, we established that newborn unanesthetized rats (2-4 days old) exposed to 10% O2 respond as other species. Their ventilation (VE), measured by flow plethysmography, immediately increased by 30%, then dropped and remained around normoxic values within 5 min. The drop was due to a decrease in tidal volume, while frequency remained elevated. Hence, alveolar ventilation was about 10% below normoxic value. At the same time O2 consumption, measured manometrically, dropped (-23%), possibly indicating a mechanism to protect vital organs. Ten percent CO2 in O2 breathing determined a substantial increase in VE (+47%), indicating that the respiratory pump is capable of a marked sustained hyperventilation. When CO2 was added to the hypoxic mixture, VE increased by about 85%, significantly more than without the concurrent hypoxic stimulus. Thus, even during the drop in VE of the biphasic response to hypoxia, the respiratory control system can respond with excitation to a further increase in chemical drive. Analysis of the breathing patterns suggests that in the newborn rat in hypoxia the inspiratory drive is decreased but the inspiratory on-switch mechanism is stimulated, hypercapnia increases ventilation mainly through an increase in respiratory drive, and moderate asphyxia induces the most powerful ventilatory response by combining the stimulatory action of hypercapnia and hypoxia.