Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)     

The ventilatory response to endogenous CO2 in preterm infants

The measurement of the ventilatory response to inhaled CO2 is unphysiologic because the CO2 that normally stimulates breathing is endogenous (tissue or venous CO2). We took advantage of the spontaneous changes in alveolar PCO2 and ventilation occurring in preterm infants during periodic breathing to calculate the ventilatory response to endogenous CO2. This response was obtained in 20 infants and compared with those obtained using the more conventional methods of steady-state inhalation of CO2 (12 infants) and rebreathing of CO2 (11 infants); it was also compared with a transient change in alveolar CO2 obtained by inhalation of 7% CO2 in air for 10 s (CO2 "bolus"; 11 infants). All groups of infants had similar birth weight and gestational ages. To calculate the response to endogenous CO2, delta PACO2 was measured as the difference between lowest and highest PaCO2 and delta VE was the difference between the corresponding instantaneous ventilation. To adjust for circulation time, values for PACO2 were made lowest for the last breath before apnea and highest for the first breath after apnea. The coefficient of variation of the method was 8%. The slope of the ventilatory response to endogenous CO2 was 0.067 +/- 0.009 (mean +/- SE) L.min-1.kg-1.mm Hg PACO2(-1), a value greater than that using steady-state and rebreathing methods (0.038 +/- 0.004 and 0.040 +/- 0.006 L.min-1.kg-1.mm Hg PACO2(-1), respectively), but similar to that of infants inhaling a CO2 "bolus" (0.051 +/- 0.009 L.min-1.kg-1.mm Hg PACO2(-1)).(ABSTRACT TRUNCATED AT 250 WORDS)     

Volume acceleration as an index of neuromuscular output

At the transition from expiration to inspiration, when flow and volume changes are small, changes in the respiratory system driving pressure could determine the degree of volume acceleration (AI), which, in turn, could reflect the degree of respiratory center output. To test this hypothesis, we calculated AI occurring in each respiratory cycle at the transition from expiration to inspiration during CO2 rebreathing in 4 healthy supine subjects. To minimize the flow and volume change over the measurement interval, we measured AI just prior to inspiration within the limits of an expiratory flow of 0.2 L . sec -1 to zero flow using digital differentiation. We also measured mouth pressure 100 msec after the onset of inspiration (P0.1) during intermittent transient inspiratory airway occlusions. During CO2 rebreathing AI increased significantly with both increasing PCO2 and P0.1. We also compared pairs of rebreathing studies, performed without and with an alinear (16 cm H2O . L -1 . sec -1) inspiratory resistor (IR), repeated twice in the 4 subjects. IR markedly decreased delta VE/delta PCO2 and the slope of the increase in mean inspiratory flow rate with PCO2 (delta VT/TI/delta PCO2) but did not significantly alter either delta AI/delta PCO2 or the increase in P0.1 with PCO2 (delta P0.1/delta PCO2). However, the effects of IR on AI and P0.1 differed between the early and late phases of each rebreathing run; early in the rebreathing runs (PCO2 = 55 Torr) IR increased both AI and P0.1 by a similar amount, but near the end of rebreathing (PCO2 = 60 Torr) IR increased P0.1 but not AI. Our results are consistent with the possibility that AI reflects neuromuscular output under the conditions of the study. Hence this approach justifies further evaluation to determine its general applicability.     

Correlation between genioglossal and diaphragmatic responses to hypercapnia during sleep

Oropharyngeal patency during sleep is dependent on the dilating force of the genioglossus, the main tongue protrusor muscle. We measured the ventilatory (Vl), diaphragmatic (EMGdi), and genioglossal (EMGgg) electromyographic responses to CO2 in awake and sleeping goats; delta Vl/delta PETCO2 decreased from awake (0.85 +/- 0.087 L/min/mm Hg) to NREM sleep (0.69 +/- 0.069) to REM sleep (0.57 +/- 0.078, p less than 0.005 versus awake). There were minimal decreases in delta EMGdi/delta PETCO2 and EMGdi at a PETCO2 of 55 mm Hg from awake to NREM, but a significant decrease in EMGdi at a PETCO2 of 55 mm Hg during REM sleep (p less than 0.025 versus NREM). Inspiratory EMGgg was only present above a PCO2 threshold, which was similar for each state (49.3 +/- 2.3 mm Hg PETCO2 awake, 48.8 +/- 2.4 during NREM, 49.5 +/- 2.5 during REM), and delta EMGgg/delta PETCO2 tended to be less during both sleep states compared with that while awake (p = 0.10). At any PCO2, inspiratory EMGgg was markedly inhibited during REM sleep when rapid eye movements were present (phasic REM). We conclude that there is disproportionate inhibition of the genioglossus relative to the diaphragm at low CO2 tensions and at any PCO2 during phasic REM sleep. This imbalance may predispose the upper airway to inspiratory occlusion during sleep.     

Role of CO2 responsiveness and breathing efficiency in determining exercise capacity of patients with chronic airway obstruction

We examined the role of CO2 responsiveness and breathing efficiency in limiting exercise capacity in 15 patients with chronic airway obstruction (FEV1 = 0.88 +/- 0.25 L, mean +/- SD). Responses of minute ventilation and P0.1 (mouth pressure 0.1 s after the onset of occluded inspiration) to hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) were measured by rebreathing, and the ratio of the two (delta VE/delta P0.1) was defined as an index of breathing efficiency during hyperventilation. Exercise capacity was measured as symptom-limited, maximal oxygen consumption (VO2max/BW) in an incremental treadmill test and also as the 12-min walking distance (TMD). All patients discontinued the treadmill test because of dyspnea, and the exercise capacity correlated with the degree of airway obstruction, although there was a wide variability among patients with comparable FEV1. There were no significant correlations between the responses to CO2 and exercise capacity. However, there was a significant correlation between delta VE/delta P0.1 and VO2max/BW (r = 0.87, p less than 0.001) or TMD (r = 0.78, p less than 0.001), and these correlations remained significant even when the relational effects of FEV1 were taken out. These results support the hypothesis that airway obstruction and breathing efficiency are important, but that CO2 responsiveness is not a major factor in determining the exercise capacity of patients with chronic airway obstruction.     

Ventilatory and waking responses to CO2 in sleeping dogs.

We examined ventilatory and waking responses to hyperoxic hypercapnia in 3 dogs during natural sleep. Progressive hypercapnia was induced by a rebreathing technique, and sleep was determined by electroencephalographic and behavioral criteria. In non-rapid eye movement sleep (high-voltage, slow-frequency electroencephalography) rebreathing continued for 0.99 +/- 0.05 min (mean +/- SE) before arousal occurred, and the alveolar PCO2, at arousal was 54.2 +/- 3.4 mm Hg. In contrast, during rapid eye movement sleep, rebreathing lasted for 1.71 +/- 0.27 min (P less than 0.05) before arousal occurred and the alveolar PCO2 at arousal was 60.3 +/- 4.2 mm Hg (P less than 0.05). Linear regression analysis of breath-by-breath instantaneous minute volume of ventilation, tidal volume, and respiratory frequency against alveolar PCO2 revealed regression coefficients in rapid eye movements sleep that were 14 to 33 per cent of those found in non-rapid eye movement sleep, and correlation coefficients of 0.26 to 0.46, compared to 0.71 to 0.91 in non-rapid eye movement sleep. Thus, the link between CO2 and ventilation appeared to be strong in non-rapid eye movement sleep but considerably disrupted during rapid eye movement sleep. We conclude that centers involved in both waking and ventilatory responses to hypercapnia behave as if they are less aware of or responsive to CO2 in rapid eye movement sleep than in non-rapid eye movement sleep.     

Effects of hydralazine on mouth occlusion pressure and ventilatory response to hypercapnia in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Hydralazine has been shown to increase minute ventilation (VE) in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The mechanism by which hydralazine produces this effect has not been defined. We investigated the effects of orally administered hydralazine on hypercapnic ventilatory response (delta VE/delta PaCO2) and central respiratory drive (delta P0.1/delta PaCO2) as well as the effects on hemodynamics, ventilation, and gas exchange in 10 male patients (mean age, 59 +/- 2 yr). The patients had a severe degree of chronic air-flow obstruction (FEV1, 1.07 +/- 0.08 L) and mild pulmonary hypertension (mean pulmonary artery pressure, 25 +/- 4 mm Hg). After hydralazine, the slope of delta VE/delta PaCO2 increased by 177% (p less than 0.005), and the slope of delta P0.1/delta PaCO2 increased by 145% (p less than 0.05). Resting ventilation increased from 14.8 +/- 1.0 to 17.1 +/- 1.4 L/min (p less than 0.02), primarily as a result of increased respiratory frequency. After hydralazine, PaO2 increased from 66 +/- 4 to 70 +/- 3 mm Hg (p less than 0.05) at rest and from 54 +/- 3 to 59 +/- 3 mm Hg (p less than 0.02) during exercise. PaCO2 decreased from 46 +/- 3 to 42 +/- 3 mm Hg (p less than 0.001) at rest and from 50 +/- 3 to 45 +/- 3 mm Hg (p less than 0.001) during exercise. No change was seen in the dead space to tidal volume ratio or the degree of venous admixture. Mean pulmonary artery pressure and total pulmonary resistance both at rest and during exercise were unchanged after hydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep deprivation decreases ventilatory response to CO2 but not load compensation

Because sleep is known to reduce ventilatory drive, and sleep deprivation is a common accompaniment to ventilatory failure, we tested ventilatory response to carbon dioxide (delta V1/delta PCO2) and response to an inspiratory flow resistive load (change in delta P100/delta PCO2 with load) after both a normal night of sleep and after 24 hours of sleep deprivation in 13 healthy volunteers. Sleep deprivation was associated with a significant decrease in delta V1/delta PCO2 from 2.51 +/- .36 to 2.09 +/- .34 L/min/mm Hg (p less than 0.02). However, load compensation was preserved during sleep deprivation. Since many acutely-ill patients are sleep deprived, an associated reduction of ventilatory drive may play a role in progressive respiratory insufficiency.     

Hypercarbic ventilatory responses of human heart-lung transplant recipients

To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition.     

Ventilatory control after pulmonary resection

Because pulmonary resection decreases pulmonary compliance, the effects of resection on ventilation might be similar to the known effects of elastic loading. We evaluated the breathing pattern and ventilatory drive in 12 patients before and after pulmonary resection with mean tissue loss of 4 segments. During resting ventilation, the only significant change after resection was a decrease in inspiratory time (Tl). At a higher level of minute ventilation (VE), induced by CO2 rebreathing, significant changes included increased respiratory frequency, decreased tidal volume and Tl, and increased occlusion pressure (P0.1). Both ventilation and occlusion pressure responses to CO2 (delta VE/delta PACO2, delta P0.1/delta PACO2) were unchanged after resection. We conclude that increased ventilation induced by CO2 rebreathing unmasks a breathing pattern after pulmonary resection which is similar to that seen with breathing against an external elastic load.     

Learning effect of repeated hypercapneic ventilatory response testing

To determine whether hypercapneic ventilatory response (HCVR) is affected by repeated testing, the HCVR of 22 healthy subjects was determined daily for 4 consecutive days. The slope (S) of the HCVR increased to a maximum on Day 3, which was 14% greater than S on Day 1 (p less than 0.05). The increase in airway occlusion pressure during progressive hypercapnea (delta P0.1/delta PCO2) showed no significant change, indicating that although S and delta P0.1/delta PCO2 are both good measurements of ventilatory response, they are not totally interchangeable in normal subjects. A subgroup of 12 subjects (termed "increasers") was responsible for the overall increase in S. For this subgroup, S was significantly smaller on Day 1 than on each subsequent day. Increasers also had a significantly greater value of S on each day of the study than subjects who did not increase ("decreasers"). On Day 1, increasers' S was 3.77 +/- 1.31 L min-1 mm Hg-1, while decreasers' S was 2.46 +/- 1.00 (p less than 0.001). Some normal subjects demonstrate a learning effect during repeated daily testing of HCVR by the rebreathing technique, and those subjects whose S increases are those with large initial values of S.     

Inspiratory muscle activity during pulmonary edema in anesthetized dogs.

Pulmonary edema is known to induce a rapid and shallow breathing pattern. However, its effects on the level and pattern of distribution of motor activity to the respiratory muscles is unclear. In the present study we evaluated the effect of oleic acid induced pulmonary edema on the electrical activity of the inspiratory muscles (costal and crural diaphragm and parasternal and external intercostal muscles) in the dog, and related it to the transdiaphragmatic pressure and ventilatory parameters over the course of CO2 rebreathing. Pulmonary edema, reflected by a 7.1 +/- 0.6 wet to dry ratio, decreased lung compliance by 57%, increased pulmonary shunt to 35%, and was associated with a rapid and shallow breathing pattern. When compared at equal levels of PCO2 during CO2 rebreathing before and during edema, ventilation and mean inspiratory flow were increased only at lower levels of hypercapnia and their responses to increasing levels of PCO2 were significantly diminished during edema. Transdiaphragmatic pressures were elevated during edema as compared to control values. The rate of rise of the electrical activity of all inspiratory muscles increased significantly during edema at all levels of PCO2. Peak activity, however, remained unchanged, due to shortening of the inspiratory duration. The EMG responses to progressive hypercapnia were not affected by edema. Pulmonary edema did not change the pattern of breathing and neural output to the inspiratory muscles in vagotomized dogs. We conclude that stimulation of pulmonary proprioreceptors during edema increases neural output to all inspiratory muscles. The neural response to hypercapnia is not altered by edema, and is additive to the vagal input. The ventilatory response to CO2 is blunted during severe edema, due to alterations in lung mechanics.     

The respiratory neuromuscular response to hypoxia, hypercapnia, and obstruction to airflow in asthma.

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.     

Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome

Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.     

A comparison of the ventilatory responses to exercise of elderly and younger humans.

Elderly adults are assumed to have an exaggerated ventilatory response to exercise. This study sought to examine this assumption by comparing the steady-state ventilatory and gas exchange responses of a group of elderly and younger humans. Steady-state ventilatory responses to moderate cycle ergometer exercise were measured in 14 elderly (71.0 +/- 1.3, mean +/- SEM years) and 14 younger (21.8 +/- 0.7 years) subjects. Compared with the younger group, the elderly had a significantly higher VE, VCO2, and VO2 at all work rates. In addition, delta VE/delta VCO2 was significantly higher for the elderly than for the younger subjects (31.07 +/- 1.34 vs 27.16 +/- 1.01, respectively; p less than .03), but the intercept with the ventilation axis was significantly lower (0.81 +/- 0.97 1.min-1 vs 4.15 +/- 0.77 1.min-1, respectively; p less than .015). Consequently, the VE-VCO2 relationships of the two groups crossed and the ventilatory equivalent for CO2 was similar for both groups. Thus, in these elderly subjects, the steeper delta VE/delta VCO2 was misleading because it was not associated with a greater ventilatory equivalent for CO2. In summary, although the ventilatory response of these elderly subjects to a given work rate was greater than that of the younger subjects, this was secondary to a greater metabolic requirement and cannot therefore be considered exaggerated. Furthermore, the data suggest that delta VE/delta VCO2 may be an inappropriate index of the ventilatory response to exercise in the elderly.     

Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea

Nineteen subjects with the obstructive sleep apnea syndrome (10 with daytime arterial CO2 tension 44 mm Hg or higher) were treated with long-term nocturnal continuous positive airway pressure. The ventilatory response to CO2 (Read's method) was measured in triplicate prior to treatment and after 1, 2, 3, 7, and 14 or more nights of therapy. Seven subjects were tested on at least 4 occasions. For each test, slope of the response line and position of the response line (ventilation at a PCO2 of 60 mm Hg) were calculated. The subjects with initial high daytime CO2 showed no change in slope of response with treatment but showed a progressive increase in ventilation at any given degree of PCO2. Ventilation at a PCO2 of 60 mm Hg increased from a mean of 20.0 +/- 1.3 SEM L/min by 8.0 +/- 2.5 SEM L/min after 2 nights of therapy (p less than 0.05, two-way analysis of variance), and by 16.2 +/- 1.9 L/min after 2 wk or more (p less than 0.01). On average, there was no significant change in either slope or position of response in the subjects with initially normal daytime PCO2. We conclude that airway obstruction in sleep (in obstructive sleep apnea syndrome) leads in some subjects to respiratory failure in the daytime, with a left shift in the ventilatory response to CO2, and that this changes is usually reversible during the next several days.     

Awake inspiratory airway occlusion in normal humans is followed by hyperpnea and hypocapnia

The ventilatory response following 15 seconds of inspiratory airway occlusion at functional residual capacity (FRC) was studied in nine normal supine awake subjects. Expired minute ventilation (VE), CO2 output (VCO2), tidal volume (VT), and end-tidal PCO2 (PETCO2) were measured on a breath-by-breath basis. Alveolar PCO2 rose 5.6 mm Hg during the apnea (P less than 0.001). Ventilation rose 10.8 L/min on the first breath following apnea and remained elevated above control measurements for five breaths (P less than 0.05). The persistent hyperpnea was due to an increase in tidal volume and was associated with alveolar hypocapnia for 6 breaths or 30 sec (P less than 0.05) and an increase in CO2 output for 4 breaths (P less than 0.05). Changes in end-tidal PCO2 correlated with excess CO2 output relative to control measurements immediately prior to airway occlusion (P less than 0.03). After 15 sec airway occlusion at FRC, there is alveolar hypercapnia with a 2.6-fold first breath rise in ventilation. Persistent alveolar hyperventilation lasting 30 sec following airway occlusion may be due to delays in central chemoreceptor response or an afterdischarge phenomenon. This overshoot hypercapnia following airway occlusion may have some relevance to the development of central apneas following obstructive apnea episodes.     

Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy

Thirty-one subjects with chronic congestive heart failure (CHF) were separated into 3 groups according to ventilatory patterns during graded exercise: Group 1--oscillators (n = 6); group 2-intermediate oscillators (n = 14); and group 3--nonoscillators (n = 11). Group 1 patients showed cyclic fluctuations in minute ventilation (change of 30 to 40 liters/min) and arterial PO2 (change of 38.0 +/- 4.1 mm Hg) and PCO2 (change of 11 +/- 2.8 mm Hg). The nadir in arterial PO2 occurred at times when wasted ventilatory effort was maximal. The amplitude of ventilatory oscillations in group 1 patients increased in the transition from rest to light exercise and damped with heavy exercise. There was no evidence of alveolar hypoventilation at the nadirs of minute ventilation; arterial PCO2 was always 40 mm Hg or less. Substantial hyperventilation (ventilatory equivalent for CO2 twice normal) occurred with maximal minute ventilation in group 1 patients. Oscillatory hyperventilation correlated with severity of CHF. Maximal oxygen uptake was significantly lower in group 1 (11.7 +/- 1.1 ml/kg/min) than group 3 (17.9 +/- 1.8 ml/kg/min) (p less than 0.05). Oscillatory hyperventilation during exercise may accompany severe CHF and compounds the inadequate delivery of oxygen by the failing heart.     

Gas transport enhancement in high-frequency oscillation

Gas transport during high-frequency oscillation (HFO) with (HFO+BT) and without bias tube (HFO-BT) was investigated in 10 anesthetized supine dogs. The oscillatory volume effectively delivered to the lungs, airway occlusion pressure and lung volume above functional residual capacity (FRC), regulated by a newly deviced pressure control system, as well as the oscillatory frequency (20 Hz) were adjusted to equal levels in HFO+BT and HFO-BT. At a fresh gas flow rate (fgf) of 3 L/min (room air), arterial CO2 partial pressures (PaCO2) decreased from 49.9 +/- 6.5 mm Hg (mean +/- SD) to 40.2 +/- 6.3 mm Hg (P less than 0.01) i.e. by 19.2 +/- 8.7%, and arterial O2 partial pressures (PaO2) increased from 71.5 +/- 13.1 mm Hg to 85.6 +/- 14.6 mm Hg (P less than 0.01) or by 20.5 +/- 12.0% in HFO-BT as compared to HFO+BT. At a fgf of 6 L/min, PaCO2 decreased less but still significantly (P less than 0.025) from 42.1 +/- 6.5 mm Hg to 37.8 +/- 6.8 mm Hg (10.4 +/- 5.6%) and PaO2 increased from 78.1 +/- 12.9 mm Hg to 84.6 +/- 16.4 mm Hg i.e. by 8.1 +/- 6.4% (P less than 0.05) in HFO-BT. The higher gas transport efficiency after removing the bias tube can be explained by two mechanisms: (1) By removing the bias tube, the volume of the bias system decreased from 54 ml in HFO+BT to 1 ml in HFO-BT and rebreathing of exhaust gas from the bias system is therefore eliminated in HFO-BT.(ABSTRACT TRUNCATED AT 250 WORDS)