Assessment of the helminth fauna in northern bobwhites (Colinus virginianus) occurring within South Texas.

Populations of northern bobwhites (Colinus virginianus; hereafter bobwhite) have been declining across their geographic range in North America, prompting consideration of the role parasites may play. We conducted this study to learn about the helminth fauna in South Texas, a region that supports a sustainable bobwhite population. Helminths were examined from 356 bobwhites collected during the 2014-2015 (n = 124) and 2015-2016 (n = 232) hunting seasons, when increasing trends in precipitation were observed in comparison with the previous two years. Ten helminth species were found, consisting of 14,127 individuals. Of these, all are heteroxenous parasites and three are pathogenic (Dispharynx nasuta, Tetrameres pattersoni and Oxyspirura petrowi). Aulonocephalus pennula numerically dominated the component community (81% prevalence, 99% of the total helminths found), whereas each of the remaining species occurred rarely (≤9% prevalence) and contributed few individuals (≤0.4%) to the helminth community. Prevalence and abundance of A. pennula were not influenced by host age, sex or body mass, but abundance was higher during the 2014-2015 than the 2015-2016 hunting season. Our findings indicate that the helminth community in bobwhites from South Texas can vary during long-term, highly variable precipitation conditions and these communities are more similar to those found in the Rolling Plains of Texas than those found in the eastern part of the bobwhite's geographic range in the US.

Rapid suppression of bone formation marker in response to sleep restriction and circadian disruption in men.

We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. INTRODUCTION: A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. METHODS: The ~ 3-week protocol included two segments: "baseline," ≥ 10-h sleep opportunity/day × 5 days; "forced desynchrony" (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20-59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (ß) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. RESULTS: Plasma P1NP levels declined significantly within the first 10 days of FD ([Formula: see text] = - 1.33 µg/L per 24 h, p < 0.0001) and remained lower than baseline with prolonged exposure out to 3 weeks ([Formula: see text] = - 0.18 µg/L per 24 h, p = 0.67). As previously reported, levels of a bone resorption marker (C-telopeptide (CTX)) were unchanged. CONCLUSION: Sleep restriction with concurrent circadian disruption induced a relatively rapid decline in P1NP (despite no change in CTX) and levels remained lower with ongoing exposure. These data suggest (1) even brief sleep restriction and circadian disruption can adversely affect bone metabolism, and (2) there is no P1NP recovery with ongoing exposure that, taken together, could lead to lower bone density over time.

Correction to: Chronotherapy for Hypertension.

The meta-analysis referenced in the "Obstructive Sleep Apnea" section should instead refer to a meta-analysis for chronic kidney disease. Additionally, there are two mis-numbered reference citations in the "chronic kidney disease" section (ref. 107 should ref. 104 [Wang C et al. 2014] and ref. 105.

Chronotherapy for Hypertension.

PURPOSE OF REVIEW: Given the emerging knowledge that circadian rhythmicity exists in every cell and all organ systems, there is increasing interest in the possible benefits of chronotherapy for many diseases. There is a well-documented 24-h pattern of blood pressure with a morning surge that may contribute to the observed morning increase in adverse cardiovascular events. Historically, antihypertensive therapy involves morning doses, usually aimed at reducing daytime blood pressure surges, but an absence of nocturnal dipping blood pressure is also associated with increased cardiovascular risk. RECENT FINDINGS: To more effectively reduce nocturnal blood pressure and still counteract the morning surge in blood pressure, a number of studies have examined moving one or more antihypertensives from morning to bedtime dosing. More recently, such studies of chronotherapy have studied comorbid populations including obstructive sleep apnea, chronic kidney disease, or diabetes. Here, we summarize major findings from recent research in this area (2013-2017). In general, nighttime administration of antihypertensives improved overall 24-h blood pressure profiles regardless of disease comorbidity. However, inconsistencies between studies suggest a need for more prospective randomized controlled trials with sufficient statistical power. In addition, experimental studies to ascertain mechanisms by which chronotherapy is beneficial could aid drug design and guidelines for timed administration.

24-hour profile of serum sclerostin and its association with bone biomarkers in men.

The osteocyte's role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. INTRODUCTION: The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. METHODS: Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. RESULTS: No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30-07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). CONCLUSIONS: Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.

Day/night variations of high-molecular-weight adiponectin and lipocalin-2 in healthy men studied under fed and fasted conditions.

AIMS/HYPOTHESIS: Adiponectin and lipocalin-2 are adipocyte-derived plasma proteins that have been proposed to have opposite effects on insulin sensitivity. Given the epidemiological, physiological and molecular links between sleep, the circadian timing system and glucose metabolism, the aim of this study was to assess effects of the sleep/wake cycle and the fasting/feeding cycle on high-molecular-weight adiponectin (HMW-adiponectin; the biologically active form) and lipocalin-2. We also aimed to compare the 24 h rhythms in the levels of these proteins with those of cortisol, leptin, leptin-binding protein and total adiponectin. METHODS: Lean men underwent a 3 day in-laboratory study, either in the fed state (n = 8, age: 20.9 ± 2.1 years, BMI: 22.8 ± 2.3 kg/m²) or fasting state (3 day fast, n = 4, age: 25.3 ± 3.9 years, BMI: 23.3 ± 2.2 kg/m²). The sleep episode was scheduled in darkness from 23:00 to 07:00 hours. Blood was sampled every 15 min for 24 h on the third day of each study. RESULTS: While fed, HMW-adiponectin and lipocalin-2 had large daily rhythms with troughs at night (HMW-adiponectin: ~04:00 hours, peak-to-trough amplitude 36%, p < 0.0001; lipocalin-2: ~04:00 hours, 40%, p < 0.0001). On the third day of fasting, the timing and relative amplitudes were unchanged (HMW-adiponectin: ~04:00 hours, 38%, p = 0.0014; lipocalin-2: ~05:00 hours, 38%, p = 0.0043). CONCLUSIONS/INTERPRETATION: These data show that HMW-adiponectin and lipocalin-2 both have significant day/night rhythms, both with troughs at night, that these are not driven by the feeding/fasting cycle, and that it is important to report and/or standardise the time of day for such assays. Further studies are required to determine whether the daily rhythm of HMW-adiponectin levels influences the daily rhythm of insulin sensitivity.

The suprachiasmatic nucleus functions beyond circadian rhythm generation.

We recently discovered that human activity possesses a complex temporal organization characterized by scale-invariant/self-similar fluctuations from seconds to approximately 4 h-(statistical properties of fluctuations remain the same at different time scales). Here, we show that scale-invariant activity patterns are essentially identical in humans and rats, and exist for up to approximately 24 h: six-times longer than previously reported. Theoretically, such scale-invariant patterns can be produced by a neural network of interacting control nodes-system components with feedback loops-operating at different time scales. However such control nodes have not yet been identified in any neurophysiological model of scale invariance/self-similarity in mammals. Here we demonstrate that the endogenous circadian pacemaker (suprachiasmatic nucleus; SCN), known to modulate locomotor activity with a periodicity of approximately 24 h, also acts as a major neural control node responsible for the generation of scale-invariant locomotor patterns over a broad range of time scales from minutes to at least 24 h (rather than solely at approximately 24 h). Remarkably, we found that SCN lesion in rats completely abolished the scale-invariant locomotor patterns between 4 and 24 h and significantly altered the patterns at time scales <4 h. Identification of the control nodes of a neural network responsible for scale invariance is the critical first step in understanding the neurophysiological origin of scale invariance/self-similarity.

Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion.

STUDY DESIGN: Case-controlled preliminary observational study. OBJECTIVE: Melatonin is usually secreted only at night and may influence sleep. We previously found that complete cervical spinal cord injury (SCI) interrupts the neural pathway required for melatonin secretion. Thus, we investigated whether the absence of night time melatonin in cervical SCI leads to sleep disturbances. SETTING: General Clinical Research Center, Brigham and Women's Hospital, Boston, USA. METHODS: In an ancillary analysis of data collected in a prior study, we assessed the sleep patterns of three subjects with cervical SCI plus absence of nocturnal melatonin (SCI levels: C4A, C6A, C6/7A) and two control patients with thoracic SCI plus normal melatonin rhythms (SCI levels: T4A, T5A). We also compared those results to the sleep patterns of 10 healthy control subjects. RESULTS: The subjects with cervical SCI had significantly lower sleep efficiency (median 83%) than the control subjects with thoracic SCI (93%). The sleep efficiency of subjects with thoracic SCI was not different from that of healthy control subjects (94%). There was no difference in the proportion of the different sleep stages, although there was a significantly increased REM-onset latency in subjects with cervical SCI (220 min) as compared to subjects with thoracic SCI (34 min). The diminished sleep in cervical SCI was not associated with sleep apnea or medication use. CONCLUSION: We found that cervical SCI is associated with decreased sleep quality. A larger study is required to confirm these findings. If confirmed, the absence of night time melatonin in cervical SCI may help explain their sleep disturbances, raising the possibility that melatonin replacement therapy could help normalize sleep in this group.

Chemoreceptive mechanisms elucidated by studies of congenital central hypoventilation syndrome.

Humans born with the condition of central hypoventilation during non-rapid eye movement sleep, termed congenital central hypoventilation syndrome (CCHS), invariably have absent or greatly diminished central hypercapnic ventilatory chemosensitivity. Genetic and pathological studies of CCHS may enable identification of the genes or areas of the central nervous system involved in the syndrome and thus implicated in central hypercapnic ventilatory chemosensitivity. Functional studies of CCHS permit a more quantitative assessment of the importance of ventilatory chemosensitivity in the regulation of breathing during wakefulness and sleep. The experimental evidence suggests that central hypercapnic ventilatory chemosensitivity is crucial in regulating alveolar ventilation during non-rapid eye movement sleep but not during rapid eye movement sleep or during many of the behaviors occurring during wakefulness. Presumably, other neural drives to breathe supervene to enable adequate ventilation. However, although physiological studies in CCHS subjects have been greatly instructive, their accurate interpretation will have to await future determination of the potential genetic and/or neuroanatomic basis of the syndrome.

Genioglossal activation in patients with obstructive sleep apnea versus control subjects. Mechanisms of muscle control.

Pharyngeal dilator muscle activation (GGEMG) during wakefulness is greater in patients with obstructive sleep apnea (OSA) than in healthy control subjects, representing a neuromuscular compensatory mechanism for a more collapsible airway. As previous work from our laboratory has demonstrated a close relationship between GGEMG and epiglottic pressure, we examined the relationship between genioglossal activity and epiglottic pressure in patients with apnea and in control subjects across a wide range of epiglottic pressures during basal breathing, negative-pressure (iron-lung) ventilation, heliox breathing, and inspiratory resistive loading. GGEMG was greater in the patients with apnea under all conditions (p < 0.05 for all comparisons), including tonic, phasic, and peak phasic GGEMG. In addition, patients with apnea generated a greater peak epiglottic pressure on a breath-by-breath basis. Although the relationship between GGEMG and epiglottic negative pressure was tight across all conditions in both groups (all R values > = 0.69), there were no significant differences in the slope of this relationship between the two groups (all p values > 0.30) under any condition. Thus, the increased GGEMG seen in the patient with apnea during wakefulness appears to be a product of an increased tonic activation of the muscle, combined with increased negative-pressure generation during inspiration.

Microgravity reduces sleep-disordered breathing in humans.

To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

Genioglossal inspiratory activation: central respiratory vs mechanoreceptive influences.

Upper airway dilator muscles are phasically activated during respiration. We assessed the interaction between central respiratory drive and local (mechanoreceptive) influences upon genioglossal (GG) activity throughout inspiration. GG(EMG) and airway mechanics were measured in 16 awake subjects during baseline spontaneous breathing, increased central respiratory drive (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic negative pressure ventilation), both prior to and following dense upper airway topical anesthesia. Negative epiglottic pressure (P(epi)) was significantly correlated with GG(EMG) across inspiration (i.e. within breaths). Both passive ventilation and IRL led to significant decreases in the sensitivity of the relationship between GG(EMG) and P(epi) (slope GG(EMG) vs P(epi)), but yielded no change in the relationship (correlation) between GG(EMG) and P(epi). During negative pressure ventilation, pharyngeal resistance increased modestly, but significantly. Anesthesia in all conditions led to decrements in phasic GG(EMG), increases in pharyngeal resistance, and decrease in the relationship between P(epi) and GG(EMG). We conclude that both central output to the GG and local reflex mediated activation are important in maintaining upper airway patency.

Phasic mechanoreceptor stimuli can induce phasic activation of upper airway muscles in humans.

1. Upper airway dilator muscles are phasically activated throughout breathing by respiratory pattern generator neurons. Studies have shown that non-physiological upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative pressure) also activate these muscles. Such reflexes may become activated during conditions that alter airway resistance in order to stabilise airway patency. 2. To determine the contribution of ongoing mechanoreceptive reflexes to phasic activity of airway dilators, we assessed genioglossal electromyogram (GG EMG: rectified with moving time average of 100 ms) during slow (physiological) oscillations in negative pressure generated spontaneously and passively (negative pressure ventilator). 3. Nineteen healthy adults were studied while awake, during passive mechanical ventilation across normal physiological ranges of breathing rates (13-19 breaths min-1) and volumes (0.5-1.0 l) and during spontaneous breathing across the physiological range of end-tidal carbon dioxide (PET,CO2; 32-45 mmHg). 4. Within-breath phasic changes in airway mechanoreceptor stimuli (negative pressure or flow) were highly correlated with within-breath phasic genioglossal activation, probably representing a robust mechanoreceptive reflex. These reflex relationships were largely unchanged by alterations in central drive to respiratory pump muscles or the rate of mechanical ventilation within the ranges studied. A multivariate model revealed that tonic GG EMG, PET,CO2 and breath duration provided no significant independent information in the prediction of inspiratory peak GG EMG beyond that provided by epiglottic pressure, which alone explained 93 % of the variation in peak GG EMG across all conditions. The overall relationship was: Peak GG EMG = 79.7 - (11.3 X Peak epiglottic pressure), where GG EMG is measured as percentage of baseline, and epiglottic pressure is in cmH2O. 5. These data provide strong evidence that upper airway dilator muscles can be activated throughout inspiration via ongoing mechanoreceptor reflexes. Such a feedback mechanism is likely to be active on a within-breath basis to protect upper airway patency in awake humans. This mechanism could mediate the increased genioglossal activity observed in patients with obstructive sleep apnoea (i.e. reflex compensation for an anatomically smaller airway).

Hypercapnia can induce arousal from sleep in the absence of altered respiratory mechanoreception.

Possible mechanisms of arousal from respiratory stimuli include changes in PO(2), PCO(2), central respiratory drive, or respiratory mechanoreceptor activity. We sought to determine whether hypercapnia alone could induce arousal from sleep in four subjects with high (>/= C3) neurologically complete spinal cord injuries while on constant positive pressure mechanical ventilation (hence, respiratory mechanoreceptor activity remained constant). Subjects were chronically hypocapnic (mean baseline PET(CO(2)) = 21 mm Hg; range, 13-30 mm Hg). On the first night, the baseline rate of spontaneous awakenings was determined by polysomnography. On night two, FI(CO(2)) was increased rapidly in stable NREM sleep. Awakenings occurred in 19 of 19 trials within 5 min, with each subject waking and complaining of shortness of breath (mean time to arousal, 115 s; range, 26-264 s). It is unlikely that these were spontaneous, as the times to awakening during hypercapnia were much higher than during baseline conditions (p < 0.05). During rapidly induced hypercapnia, PET(CO(2)) overestimates the PCO(2) at the central chemoreceptors. To determine more precisely the PET(CO(2)) arousal threshold, PET(CO(2)) was increased slowly (approximately 2 mm Hg/min); arousal occurred at a mean PET(CO(2)) of 37 mm Hg (range, 23-45 mm Hg; mean change from baseline, 15.8 mm Hg, range, 10-20 mm Hg). Hence, both rapid and slow increases in PET(CO(2)) can induce arousal in humans in the absence of changes in respiratory mechanoreceptor activity.

Endogenous circadian rhythm of pulmonary function in healthy humans.

Numerous studies have demonstrated a diurnal rhythm in indices of pulmonary function in both healthy subjects and subjects with asthma, with minima occurring during the night. To determine whether such diurnal changes are caused by an endogenous circadian rhythm or by diurnal alterations in behavior or the environment, we measured indices of pulmonary function throughout a "constant routine" protocol designed to unmask underlying circadian rhythms. After two acclimation days in the laboratory, 10 healthy adults maintained relaxed wakefulness in a semirecumbent posture in a constant environment with low light (10 lux) for 41 h. Measurements of FEV(1), FEVC, PEF, blood cortisol, and core body temperature (CBT) were performed every 2 h. Results of cosinor analysis of group data aligned to CBT circadian minimum revealed significant circadian variations in FEV(1) and FEV(1)/FEVC, cortisol, and CBT, and lack of significant circadian variations in FEVC and PEF. The ranges (peak to trough) of mean circadian changes in spirometric variables were 2. 0-3.2% of the mesor. The circadian minima of all variables occurred within the usual sleep period (although subjects remained awake). Because of differences in phase relationships between CBT and pulmonary function among subjects, the circadian rhythms within subjects were generally larger than the group average circadian changes, being significant for FEV(1)/FEVC in 5 of 10 subjects and for PEF in 6 of 10 subjects. Sleep deprivation (24 h) failed to cause a significant change in any pulmonary function variable (when controlled for circadian phase). Thus, endogenous circadian rhythms contribute to diurnal changes in pulmonary function in healthy subjects.

Genioglossal but not palatal muscle activity relates closely to pharyngeal pressure.

The stimuli controlling pharyngeal dilator muscles are poorly defined. Local mechanoreceptors are a leading possibility. To address this, we assessed the relationship between two dilator muscle electromyograms (EMGs, i.e., genioglossus [GG-an inspiratory phasic muscle], tensor palatini [TP-a tonically active muscle]) and potential stimuli (i.e., epiglottic pressure [Pepi], airflow [V], and pharyngeal resistance [Rpha]). Fifteen normal subjects were studied, during wakefulness and stable non-rapid eye movement (NREM) sleep. The GGEMG and TPEMG were assessed during basal breathing and during inspiratory resistive loading (four loads, done in triplicate), while quantifying Pepi and choanal pressures (Pcho, Millar catheters) plus V. There was a strong correlation between Pepi and GGEMG during wakefulness in most subjects (9 of 15 had absolute R > 0.7 [p < 0.05], group mean R = -0.62, p < 0.05). These correlations were less robust during NREM sleep (8 of 15 absolute R > 0.6 [p < 0.05], group mean R = -0.39, ns). The slope of the Pepi versus GGEMG relationship was greater during wakefulness than sleep (-0.67 versus -0.39% max/ cm H(2)O, p < 0.05). No significant correlations were observed between TPEMG and any of the measured potential stimuli. We conclude that intrapharyngeal pressure may modulate genioglossus activity during wakefulness, with a fall in muscle responsiveness during sleep. The activity of the TP was not clearly influenced by any measured local stimulus either awake or asleep.

Upper airway muscle responsiveness to rising PCO(2) during NREM sleep.

Although pharyngeal muscles respond robustly to increasing PCO(2) during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO(2)-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal PCO(2) (PET(CO(2))) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO(2) (PET(CO(2)) = 6 Torr above the eupneic level) were also assessed during SWS (n = 9) or stage 2 sleep (n = 7). PET(CO(2)) increased spontaneously by 0.8 +/- 0.1 Torr from stage 2 to SWS (from 43.3 +/- 0.6 to 44.1 +/- 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 +/- 0.1 to 11.9 +/- 0.3 l/min in stage 2 and 8.6 +/- 0.4 to 12.7 +/- 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of PET(CO(2)) (50.4 +/- 1.6 Torr in stage 2, and 50.4 +/- 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.

Acute changes in carbon dioxide levels alter the electroencephalogram without affecting cognitive function.

The partial pressure of carbon dioxide in the arterial blood (PaCO2) is usually tightly regulated, yet it varies among healthy people at rest (range approximately 32-44 mmHg) as well as within an individual during many natural life situations. The present study examined whether modest changes in end-tidal PCO2 (PETCO2; a noninvasive measure of PaCO2) affect electroencephalographic (EEG) activity, cognitive function, and vigilance. Nine adults were ventilated mechanically using a mouthpiece; respiratory rate and breath size were held constant while PETCO2 was set to levels that produced minimal discomfort. Despite discrete changes in EEG, neither acute PETCO2 increases (mean = 47 mmHg) nor decreases (mean = 30 mmHg) from resting levels (mean = 38 mmHg) affected performance on cognitive tasks, latency or amplitude of the N1, P2, or P3 event-related potential, or alertness. Modest changes in PETCO2 may cause significant alterations in the EEG without disturbing cognitive function.

Influence of chemoreceptor stimuli on genioglossal response to negative pressure in humans.

Genioglossal muscle (GG) activity is modulated by both chemoreceptive and mechanoreceptive reflexes that help stabilize airway patency. We assessed the effects of blood gas changes, within the range encountered during mild obstructive apnea-arousal cycles, on GG activity and the GG reflex to upper airway negative pressure. Eighteen healthy adults were studied while awake under 5 conditions: (1) baseline (PET(CO(2)) = 40 mm Hg, Sa(O(2)) = 99%); (2) hypercapnia (PET(CO(2)) = 45 mm Hg); (3) hypocapnia (PET(CO(2)) = 35 mm Hg, induced via hyperventilation with an iron lung ventilator); (4) hypoxia (Sa(O(2)) = 87%); and (5) hypercapnia plus hypoxia (PET(CO(2)) = 45 mm Hg, Sa(O(2)) = 87%). Measurements included airflow, choanal and epiglottic pressures (Pchoa and Pepi), upper airway resistance, phasic and tonic GG EMG, and the GG reflex to negative pressure (Pchoa = -12.5 cm H(2)O). Ventilation increased from a baseline of 10.7 up to 22.7 L. min(-1) under conditions of altered blood gases. Peak inspiratory phasic GG EMG increased from 6. 5 to 11.1% of maximal contraction but there were no significant changes in either tonic GG EMG (range, 4.3 to 5.8% of maximum) or magnitude of the GG reflex (range, 4.1 to 5.5% of maximum). Among conditions there was a high correlation between upper airway pressures and peak phasic GG EMG (Pchoa, r = 0.97, p < 0.01; Pepi, r = 0.87; p = 0.06). We conclude that in this range of blood gases: (1) the GG reflex to negative pressure is unchanged; (2) slow airway pressure changes throughout inspiration, generated either actively or passively, influence GG EMG activity; and (3) mechanoreceptive control of GG EMG can fully explain all changes in GG activity, suggesting that chemoreceptive inputs to GG are minimal, or are not simply summated with mechanoreceptor inputs.