Ventilatory Phase Research Articles

Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice

The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

Distinct Patterns of Hyperpnea During Cheyne-Stokes Respiration: Implication for Cardiac Function in Patients With Heart Failure.

In heart failure (HF), we observed two patterns of hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive pattern where end-expiratory lung volume remains at or above functional residual capacity, and a negative pattern where it falls below functional residual capacity. We hypothesized the negative pattern is associated with worse HF. Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea, apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and left ventricular ejection fraction (LVEF) were assessed. Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a negative hyperpnea pattern. There was no difference in age, body mass index, and apnea-hypopnea index between groups. Patients with a negative pattern had longer hyperpnea time (39.5 ± 6.4 versus 25.8 ± 5.9 seconds, P < .01), longer cycle time (67.8 ± 15.9 versus 51.7 ± 9.9 seconds, P < .01), higher NT-proBNP concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York Heart Association class (P = .02) than those with a positive pattern. LFCT and LVEF did not differ between groups. Patients with HF and a negative CSR-CSA pattern have evidence of worse cardiac function than those with a positive pattern. Greater positive expiratory pressure during hyperpnea is likely generated during the negative pattern and might support stroke volume in patients with worse cardiac function. A commentary on this article appears in this issue on page 1227. The trial is registered with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and Clinical Trials (www.clinicaltrials.gov; NCT01128816).

Ventilatory Cycle Measurements and Loop Gain in Central Apnea in Mining Drivers Exposed to Intermittent Altitude.

By measuring the apnea length, ventilatory phase, respiratory cycle length, and loop gain, we can further characterize the central apneas of high altitude (CAHA). Sixty-three drivers of all-terrain vehicles, working in a Peruvian mine located at 2,020 meters above sea level (MASL), were evaluated. A respiratory polygraph was performed in the first night they slept at high altitude. None of the subjects were exposed to oxygen during the test or acetazolamide in the preceding days of the test. Sixty-three respiratory polygraphs were performed, and 59 were considered for analysis. Forty-six (78%) were normal, 6 (10%) had OSA, and 7 (12%) had CAHA. Key data from subjects include: residing altitude: 341 ± 828 MASL, Lake Louise scoring: 0.4 ± 0.8, Epworth score: 3.4 ± 2.7, apneahypopnea index: 35.7 ± 19.3, CA index: 13.4 ± 14.2, CA length: 14.4 ± 3.6 sec, ventilatory length: 13.5 ± 2.9 sec, cycle length: 26.5 ± 4.0 sec, ventilatory length/CA length ratio 0.9 ± 0.3 and circulatory delay 13.3 ± 2.9 sec. Duty ratio media [ventilatory duration/cycle duration] was 0.522 ± 0 0.128 [0.308-0.700] and loop gain was calculated from the duty ratio utilizing this formula: LG = 2π / [(2πDR-sin(2πDR)]. All subjects have a high loop gain media 2.415 ± 1.761 [1.175-6.260]. Multiple correlations were established with loop gain values, but the only significant correlation detected was between central apnea index and loop gain. Twelve percent of the studied population had CAHA. Measurements of respiratory cycle in workers with CAHA are more similar to idiopathic central apneas rather than Hunter-Cheyne-Stokes respiration. Also, there was a high degree of correlation between severity of central apnea and the degree of loop gain. The abnormal breathing patterns in those subjects could affect the sleep quality and potentially increase the risk for work accidents.

Unbuckling the Buccal oscillator in the American Bullfrog

The American Bullfrog is a remarkable model organism to study rhythm generation underlying breathing. It exhibits a breathing pattern that can be divided into four distinct ventilatory phases: lung‐priming, lung‐powerstroke, buccal‐dilation, and buccal‐constriction. We recently established that lung‐priming and lung‐powerstroke are generated by two separate burst generating substrates in the brainstem—the Priming area and Powerstroke area—located in rhombomere 4–5. The neural origin of the two phases of buccal, on the other hand, remains elusive. Our previous experiments suggest that a Buccal area located in rhombomere 7 is responsible, at least in part, for generating the biphasic buccal rhythm; however, whether any additional burst generating substrates are involved is yet unknown.The objective of this study was to characterize areas in the frog brainstem that generate the biphasic buccal rhythm. We utilized the isolated frog brainstem preparation and recorded fictive respiratory motor output from the trigeminal and facial cranial nerves using extracellular suction electrodes. We progressively transected the brainstem in both directions (caudal‐to‐rostral, and rostral‐to‐caudal) to identify regions where transection eliminated one or both buccal burst phases.Our preliminary results suggest that both phases of the buccal rhythm are generated by substrates located at the same level as the previously identified Buccal area. Nevertheless, using our current methodology, we are unable to discern whether multiple substrates or a single substrate is generating the buccal rhythm. To address this question, we developed a ‘buccal slice’ preparation at the level of the Buccal area which, when exposed to 100nM AMPA, produces buccal‐like bursts. We continue to develop this preparation as it holds promise for further dissecting the properties of this system and exploring it at the cellular and molecular levels.Our analysis suggests that the Buccal area is an evolutionary homolog of the mammalian preBötzinger complex. Both are located in rhombomere 7, are resilient oscillators, being staunchly insensitive to CO2, and co‐opted for sniffing. We anticipate that having two comparable preparations, i.e. ‘buccal slice’ and ‘preBötC slice’, will allow for more direct comparisons between these oscillators, further testing their homology and thus take us closer towards understanding the evolution of breathing.Support or Funding InformationNational Science and Engineering Council of Canada (NSERC) and Alberta Innovates Health Solutions (AIHS) provided funding for this study.

Influence of respiratory frequency in measurement of specific airway conductance during non-panting breathing

In order to investigate the influence of respiratory frequency in the measurement of specific airway conductance (sGaw) during non-panting breathing, we examined specific airway conductance using a body plethysmograph (BX-82, Minato) in 20 stable pulmonary emphysema patients and 19 normal control subjects. Our body plethysmograph device can measure sGaw automatically without panting by making various corrections using a 16-bit microcomputer. We measured sGaw first at a flow of 0.5 L/sec during both inspiratory and expiratory ventilatory phases, then the respiratory frequency was changed from 0.5 to 1.0, 1.5 and 2.0 Hz. In normal control subjects sGaw, tidal volume and mouth flow significantly changed by increasing respiratory frequency, and there was a significant correlation between sGaw and mouth flow. In pulmonary emphysema patients, tidal volume decreased significantly by increasing respiratory frequency, and there was a significant correlation between sGaw and tidal volume, but sGaw and mouth flow did not change significantly by increasing respiratory frequency. These results suggest that specific airway conductance is influenced by respiratory frequency, possibly due to the change in tidal volume and mouth flow. It is necessary to standardize respiratory frequencies and mouth flows in the measurement of specific airway conductance during non-panting breathing.

Continuous positive airway pressure reduces loop gain and resolves periodic central apneas in the lamb

Continous positive airway pressure (CPAP) is used to treat infant respiratory distress syndrome and apnea of prematurity, but its mode of action is not fully understood. We hypothesised that CPAP increases lung volume and stabilises respiratory control by decreasing loop gain (LG). Experimentally induced periodic breathing (PB) in the lamb was terminated early by CPAP in a dose-dependent manner, with a control epoch of 45.4+/-5.1s at zero CPAP falling to 32.9+/-5.4, 13.2+/-4.2 and 9.8+/-3.1s at 2.5, 5 and 10 cmH(2)O, respectively (p<0.001); corresponding duty ratios (duration of the ventilatory phase of PB divided by its cycle duration) increased from 0.50+/-0.02 to 0.62+/-0.05, 0.76+/-0.06 and 0.68+/-0.08, respectively (p<0.001). Since epoch duration and duty ratio are surrogate measures of LG, we conclude that CPAP ameliorates the effects of recurrent central apneas, and perhaps mixed and obstructive apneas, by decreasing LG via increases in lung volume.

Coordination between ventilatory pressure oscillations and venous return in the cephalopod Sepia officinalis under control conditions, spontaneous exercise and recovery

Venous blood flow was measured for the first time in a cephalopod. Blood velocity was determined in the anterior vena cava (AVC) of cuttlefish S. officinalis with a Doppler, while simultaneously, ventilatory pressure oscillations were recorded in the mantle cavity. In addition, magnetic resonance imaging (MRI) was employed to investigate pulsatile flow in other major vessels. Blood pulses in the AVC are obligatorily coupled to ventilatory pressure pulses, both in frequency and phase. AVC peak blood velocity (v(AVC)) in animals of 232 (+/- 30 SD) g wet mass at 15 degrees C was found to be 14.2 (+/- 7.1) cm s(-1), AVC stroke volume (SV(AVC)) was 0.2 (+/- 0.1) ml stroke(-1), AVC minute volume (MV(AVC)) amounted to 5.5 (+/- 2.8) ml min(-1). Intense exercise bouts of 1-2 min resulted in 2.2-fold increases in MV(AVC), enabled by 1.6-fold increments in both, AVC pulse frequency (f (AVC)) and v(AVC). As increases in blood flow occurred delayed in time by 1.7 min with regard to exercise periods, we concluded that it is not direct mantle cavity pressure conveyance that drives venous return in this cephalopod blood vessel. However, during jetting at high pressure amplitude (> 1 kPa), AVC blood flow and mantle cavity pressure pulse shapes completely overlap, suggesting that under these conditions, blood transport must be driven passively by mantle cavity pressure. MRI measurements at 15 degrees C also revealed that under resting conditions, f (AVC )and ventilation frequency (f (V)) match at 31.6 (+/- 2.1) strokes min(-1). In addition, rates of pulsations in the cephalic artery and in afferent branchial vessels did not significantly differ from f (AVC) and f (V). It is suggested that these adaptations are beneficial for high rates of oxygen extraction observed in S. officinalis and the energy conserving mode of life of the cuttlefish ecotype in general.

Dynamic small animal lung imaging via a postacquisition respiratory gating technique using micro-cone beam computed tomography 1

Micro computed tomography is an important tool for small animal imaging. On many occasions, it is desirable to image lungs in a live instead of postmortem small animal to perform a pulmonary physiology study. Because the lungs are moving, gating with respect to the ventilatory phase has to be performed to reduce motion artifacts. Precapture ventilation gating may be difficult to achieve in some situations, which motivates us to propose and implement a simple postacquisition gating method. Rats were used as the subjects in this study. A sequence of low-dose projection images were acquired at 30 frames per second for each view angle. During each capture sequence the rat undergoes multiple ventilation cycles. Using the sequence of projection images, an automated region of interest algorithm, based on integrated grayscale intensity, tracts the ventilatory phase of the lungs. In the processing of an image sequence, multiple projection images are identified at a particular phase and averaged to improve the signal-to-noise ratio. The resulting averaged projection images from different view angles are input to a Feldkamp cone-beam algorithm reconstruction algorithm to obtain isotropic image volumes. Reconstructions with reduced movement artifacts are obtained. In the gated reconstruction, registration of the bone is much better, the edge of the lung is clearly defined, and structures within the lung parenchyma are better resolved. Also, different phases of a breathing cycle can be reconstructed from one single tomographic scan by the proposed gating method. A postacquisition gating method using the phase information encoded in the 2-dimensional cone beam projections is proposed. This method is simple to implement and does not require additional experimental set-up to monitor the respiration. It may find applications in lung tumor detection, dynamic pulmonary physiology studies, and the respiratory systems modeling. Minimal motion artifact data sets improve qualitative and quantitative analysis techniques that are useful in physiologic studies of pulmonary structure and function.

Sleep apnea in renal patients.

In Western societies, sleep apnea (SA) has emerged as a major medical problem with important social ([1][1]) and financial implications. The issue may be even more relevant in nephrology because some of the factors involved in the pathogenesis of renal disease are the same that cause, or are

Blood pressure and heart rate during periodic breathing while asleep at high altitude

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.

Assessment of pulmonary mechanics and breathing patterns during posturally induced glossoptosis in infants.

Respiratory mechanics were studied in nine infants with glossoptosis-apnoea syndrome to determine whether glossoptosis may account for signs of both inspiratory and expiratory airway obstruction. Airflow, oesophageal pressure, inspiratory and expiratory time (Ti and Te), and inspiratory and expiratory resistance (Ri and Re) were measured before and during ventilatory phases characterised by glossoptotic pharyngeal obstruction, induced by turning the infants onto their backs. In addition, an attempt was made to correlate the abnormalities in pulmonary mechanics with the clinical features. During partial glossoptotic pharyngeal obstruction, a significant increase was observed in Te and Re and variable changes in Ti and Ri. During severe obstruction, the infants displayed obstructed inspiratory efforts often associated with stridor, as well as obstructed expiratory efforts often associated with audible grunting and retarded expiratory flow pattern. The expiratory grunt was loudest over the neck and mimicked bronchospasm over the chest. These findings indicate that glossoptotic pharyngeal obstruction induces functional airway obstruction which may affect both inspiration and expiration. Expiratory airway obstruction seems, at least in part, to be due to active braking of expiratory flow.

Upper Airway Muscle Activity During REM and Non-REM Sleep of Patients With Obstructive Apnea

We measured electromyograms (EMGs) of genioglossus muscle (GG) and inspiratory intercostal muscle (IIM) in both rapid eye movement (REM) sleep and non-REM sleep of 12 patients with obstructive sleep apnea (OSA) to examine the influence of different sleep stages on upper airway muscle activity during sleep apnea. Quantifications of both muscle activities were assessed by their individual peak amplitude of integrated inspiratory EMG. Genioglossus and IIM activities showed a qualitatively similar cyclic change with an alteration of apneic and ventilatory phases during both non-REM and REM sleep. Both muscle activities increased gradually in the late apneic phase and reached each peak at the opening of the upper airway and, subsequently, decreased gradually. There were no significant differences in both muscles activities in either the ventilatory or early apneic phase between non-REM sleep and REM sleep. On the other hand, GG and IIM activities in the late apneic phase during REM sleep were significantly lower than those during non-REM sleep. The relative activity of GG to IIM in the late apneic phase was significantly lower during REM sleep than that during non-REM sleep. These results indicate that upper airway and intercostal muscle activation in the later apneic phase during REM sleep were inhibited compared with those during non-REM sleep and that this inhibition was observed predominantly in upper airway muscles.

Neural organization of the ventilatory activity in the frog, Rana catesbeiana. II

The paralyzed, decerebrate frog, Rana catesbeiana, displays "fictive" oropharyngeal and pulmonary ventilations. In order to evaluate the neuronal correlates of these two centrally programmed ventilatory bursting patterns, we have performed intra- and extracellular recordings of bulbar respiratory neurons in this fictively breathing preparation. A total of 123 respiratory neurons were recorded from the caudal medulla. Of 51 antidromically activated neurons, 20 were vagal motoneurons and 31 were hypoglossal motoneurons. Respiratory neurons that depolarized during the lung (L) or non-lung (N) ventilatory phases were classified as L or N neurons, respectively. Phase spanning neurons (S) were active during both L and N phases. Some neurons showed oscillations of membrane potential synchronous with oropharyngeal ventilation. Those active during the buccal elevation phase were exclusively L neurons, whereas those having buccal depressor activity were exclusively N neurons. Synaptic drive potentials were observed in all neurons recorded intracellularly. In some neurons, hyperpolarization was caused by inhibitory postsynaptic potentials, as demonstrated by reversal of membrane potential trajectory after intracellular chloride iontophoresis. Some individual motoneurons and interneurons exhibited both pulmonary and buccal ventilatory activity, indicating that both pattern generators project to a common motor control system.

Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea.

Central apneas during sleep may arise as a result of reduction in PaCO2 below the apnea threshold. We therefore hypothesized that hyperventilation and arousals from sleep interact to cause hypocapnia and subsequent central apneas in patients with idiopathic central sleep apnea (ICSA). Accordingly, the relationships among preapneic ventilation, arousal from sleep, and the onset and duration of subsequent central apneas were examined during Stage 2 non-REM sleep in eight patients with ICSA (mean +/- SEM, 45.4 +/- 4.7 central apneas and hypopneas/h of sleep). During Stage 2 sleep, all episodes of periodic breathing with central apneas were triggered by hyperventilation. Minute ventilation (VI) was greater (6.3 +/- 0.7 versus 5.4 +/- 0.8 L/min, p < 0.05) and mean transcutaneous PCO2 (PtcCO2) was lower (37.8 +/- 1.3 versus 38.9 +/- 1.6 mm Hg, p < 0.05) during periodic breathing than during stable breathing. VI during the ventilatory phase of the periodic breathing cycle increased progressively with increasing grades of associated arousals from Grade 0 (no arousal) (10.3 +/- 1.4 L/min) to Grade 1 (EEG arousal) (12.6 +/- 1.6 L/min) to Grade 2 (movement arousal) (14.1 +/- 1.6 L/min, p < 0.01). There was a corresponding progressive increase in central apnea length following the ventilatory period from no arousal (14.1 +/- 2.0) to EEG arousal (16.4 +/- 1.8) to movement arousal (18.1 +/- 2.0 s, p < 0.01). We conclude that arousals and hyperventilation interact to trigger hypocapnia and central apneas in ICSA.

Physiologic Demands of Prolonged Cardiopulmonary Resuscitation Performance by Physically Conditioned Patients With Cardiac Disease

Thirteen men with cardiac disease who were 37 to 71 years of age (mean, 58 years of age) and who had been aerobically conditioned for at least 6 weeks in a cardiac rehabilitation program were studied to determine whether they could safely perform 10 minutes of sustained cardiopulmonary resuscitation (CPR). Hemodynamic, metabolic, and electrocardiographic (ECG) changes were observed during 10 minutes of single-person CPR (compression and ventilatory phases) to determine if sign /symptomatic response occurred and the exertional effort the responses required. No subjects had serious arrhythmias or significant ST segment changes during CPR performance that were not apparent during exercise training. The highest mean energy cost was 11.4 mL · Kg-1 · min-1 (3.26 METS), measured at minute 6 of CPR performance. Heart rate (HR) peaked at minute 5 (32 beats per minute above resting values), and the rate-pressure product (RPP) increased progressively during CPR performance, achieving an increase of 47 units at minute 10. These responses were within normally prescribed exercise limits and indicated that these selected patients could safely perform prolonged CPR.

Accuracy of central venous pressure monitoring in the intraabdominal inferior vena cava: A canine study

To test the hypotheses that in multiple pathophysiologic settings (1) end-expiratory central venous pressure measurements in the intraabdominal inferior vena cava accurately reflect those in the superior vena cava and (2) mean central venous pressure monitoring is as reliable in the inferior vena cava as it is in the superior vena cava. Simultaneous inferior vena caval and superior vena caval pressures were measured during five ventilatory phases: apnea, end-expiratory mechanical ventilation, maximal inspiratory mechanical ventilation, end-expiratory spontaneous ventilation, and maximal inspiratory spontaneous ventilation. Measurements were repeated after progressive intravascular volume depletion. Eight puppies. Simultaneous inferior vena caval and superior vena caval end-expiratory pressures did not differ significantly (mean differences 0 to 0.1 mm Hg) and the limits of agreement of these measurements were within 2 mm Hg. Differences between mean maximal inspiratory pressures in the inferior vena cava and superior vena cava during mechanical and spontaneous ventilation were -0.7 and 3.6 mm Hg, respectively (p less than 0.01), and the limits of agreement extended beyond 2 mm Hg. Furthermore, mean maximal inspiratory pressures in the superior vena cava differed from end-expiratory pressures in the superior vena cava (1.1 and -3.6 mm Hg, p less than 0.01), whereas those in the inferior vena cava did not differ from end-expiratory superior vena caval pressures. Under the experimental conditions studied (1) end-expiratory intraabdominal inferior vena caval pressures accurately reflected end-expiratory superior vena caval pressures and (2) mean central venous pressure monitoring was as reliable in the inferior vena cava as in the superior vena cava.

Right ventricular function assessed by thermodilution technique during apnea and mechanical ventilation

To evaluate strategies for thermodilution-based measurement of cardiac output and right ventricular (RV) ejection fraction and to assess the effects of controlled mechanical ventilation in patients. Furthermore, to compare strategy-associated reproducibility with reference values obtained during long-term apnea. Crossover trial in patients; reference values from apneic animals. University ICU and physiology laboratory. Six consecutive male ICU patients (48 to 70 yrs) after major abdominal vascular surgery. two adult female sheep. Three ventilatory rates (8, 16, and 24 cycles/min) and 15-sec periods of apnea were selected for measurements in patients. In animals, continuous apnea was achieved with extracorporeal CO2 removal and apneic oxygenation. Measurements were performed using an appropriate pulmonary artery catheter and an ejection fraction/cardiac output computer prototype. The thermal indicator was injected automatically at four defined points of the ventilatory cycle, but triggered manually during apnea. At 8 cycles/min, there was a wide mean range of cyclic variable modulation, with a coefficient of variation of 11.6% and 23.2% for cardiac output and RV ejection fraction, respectively. Allowing for ventilatory phase or changing from 8 to 16 cycles/min reduced errors by half. Combining both procedures resulted in a coefficient of variation of 4.7% and 6.6% for cardiac output and RV ejection fraction, respectively. The best coefficient of variation values obtained during 15 secs of apnea in patients approached those variations in experimental apnea (coefficient of variation of 2.1% and 4.5% for cardiac output and RV ejection fraction, respectively). At low ventilatory rates, best results are achieved by averaging four phase-selected measurements. One-point measurements were less accurate and random point measurements less reproducible.

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)

Airway obstruction during periodic breathing in premature infants.

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.

Changes in end-expiratory lung volume during sleep in patients with occlusive apnea.

Eight patients with occlusive sleep apnea were monitored during non-rapid-eye-movement (NREM) sleep to study the factors that contribute to negative inspiratory pressure generation and thus upper airway occlusion. End-expiratory lung volume assessed by respiratory inductive plethysmography [sum of end-expiratory levels (SUM EEL)] increased early and decreased late during the ventilatory phases (P less than 0.0001, one-way analysis of variance). Inspiratory change in esophageal pressure (Pes) and peak inspiratory diaphragmatic and genioglossal electromyograms (EMGdi and EMGge) decreased while the inspiratory pressure generated for a given diaphragmatic activity (Pes/EMGdi) increased during the preapneic phase (P less than 0.0001, for all). Multiple regression analysis with Pes/EMGdi as the dependent variable (R2 = 0.90) indicated that both the changes in SUM EEL and EMGge significantly contributed to the model (P less than 0.008 and 0.004, respectively). These results indicate that end-expiratory lung volume fluctuates during NREM sleep in patients with occlusive apnea and suggest that these changes along with the changes in upper airway muscle activity contribute to the generation of negative inspiratory pressure, leading to the passive collapse of the upper airways.