Abstract: This review focuses on two phenomena that are initiated during and after exposure to intermittent hypoxia. The two phenomena are referred to as long-term facilitation and progressive augmentation of respiratory motor output. Both phenomena are forms of respiratory plasticity. Long-term facilitation is characterized by a sustained elevation in respiratory activity after exposure to intermittent hypoxia. Progressive augmentation is characterized by a gradual increase in respiratory activity from the initial to the final hypoxic exposure. There is much speculation that long-term facilitation may have a significant role in individuals with sleep apnoea because this disorder is characterized by periods of upper airway collapse accompanied by intermittent hypoxia, one stimulus known to induce long-term facilitation. It has been suggested that activation of long-term facilitation may serve to mitigate apnoea by facilitating ventilation and, more importantly, upper airway muscle activity. We examine the less discussed but equally plausible situation that exposure to intermittent hypoxia might ultimately lead to the promotion of apnoea. There are at least two scenarios in which apnoea might be promoted following exposure to intermittent hypoxia. In both scenarios, long-term facilitation of upper airway muscle activity is initiated but ultimately rendered ineffective because of other physiological conditions. Thus, one of the primary goals of this review is to discuss, with support from basic and clinical studies, whether various forms of respiratory motor neuronal plasticity have a beneficial and/or a detrimental impact on breathing stability in individuals with sleep apnoea.

Abstract: Following exposure to intermittent hypoxia respiratory motor activity and sympathetic nervous system activity may persist above baseline levels for over an hour. The present investigation was designed to determine whether sustained increases in minute ventilation and sympathovagal (S/V) balance, in addition to sustained depression of parasympathetic nervous system activity (PNSA), were greater in males compared to females following exposure to intermittent hypoxia. Fifteen healthy males and females matched for age, race and body mass index were exposed to 8 - 4 minute episodes of hypoxia during sustained hypercapnia followed by a 15 minute end recovery period. The magnitude of the sustained increase in minute ventilation during the end-recovery period, compared to baseline, was similar in males and females (males - 1.52 +/- 0.03; females - 1.57 +/- 0.02 fraction of baseline; p < 0.0001). In contrast, depression of PNSA and increases in S/V were evident during the end recovery period, compared to baseline, in males (PNSA - 0.66 +/- 0.06 fraction of baseline, p < 0.0001; S/V - 2.8 +/- 0.7 fraction of baseline, p < 0.03) but not in females (PNSA - 1.27 +/- 0.19 fraction of baseline, p = 0.3; S/V balance - 1.8 +/- 0.6 fraction of baseline, p = 0.2). We conclude that a sustained increase in minute ventilation is evident in both males and females following exposure to intermittent hypoxia and that this response is independent of gender. In contrast, sustained alterations in autonomic nervous system activity were evident in males but not in females. Key words: carbon dioxide, parasympathetic nervous system, sympathovagal balance.

Abstract: We hypothesized that very brief episodes of hypoxia (<1min) would evoke long-term facilitation (LTF) in individuals free of inspiratory flow limitation (IFL). We studied 12 healthy participants who were self-reported non-snorers and confirmed the absence of IFL. We induced 15 brief episodes of hypoxia during non-REM sleep, reducing arterial oxygen saturation to 84-85%, followed by 1min of room air. Ventilatory variables and resistance were measured during the control period, hypoxic trials, room air controls, and for 20min following the last hypoxic episode. There was a significant increase in minute ventilation (108+/-1.3% of control, P<0.05) and tidal volume (105+/-1.7% of control, P<0.05) and a significant decrease in upper airway resistance (88+/-9.8% control, P<0.05) during the recovery period. However, there were no significant changes in any variable during sham studies. We have shown for the first time that LTF can be elicited in sleeping humans free of IFL.

Abstract: We hypothesized that the ventilatory threshold and sensitivity to carbon dioxide in the presence of hypoxia and hyperoxia during wakefulness would be increased following testosterone administration in premenopausal women. Additionally, we hypothesized that the sensitivity to carbon dioxide increases following episodic hypoxia and that this increase is enhanced after testosterone administration. Eleven women completed four modified carbon dioxide rebreathing trials before and after episodic hypoxia. Two rebreathing trials before and after episodic hypoxia were completed with oxygen levels sustained at 150 Torr, the remaining trials were repeated while oxygen was maintained at 50 Torr. The protocol was completed following 8-10 days of treatment with testosterone or placebo skin patches. Resting minute ventilation was greater following treatment with testosterone compared with placebo (testosterone 11.38 +/- 0.43 vs. placebo 10.07 +/- 0.36 l/min; P < 0.01). This increase was accompanied by an increase in the ventilatory sensitivity to carbon dioxide in the presence of sustained hyperoxia (VSco(2)(hyperoxia)) compared with placebo (3.6 +/- 0.5 vs. 2.9 +/- 0.3; P < 0.03). No change in the ventilatory sensitivity to carbon dioxide in the presence of sustained hypoxia (VSco(2 hypoxia)) following treatment with testosterone was observed. However, the VSco(2 hypoxia) was increased after episodic hypoxia. This increase was similar following treatment with placebo or testosterone patches. We conclude that treatment with testosterone leads to increases in the VSco(2)(hyperoxia), indicative of increased central chemoreflex responsiveness. We also conclude that exposure to episodic hypoxia enhances the VSco(2 hypoxia), but that this enhancement is unaffected by treatment with testosterone.

Abstract: The American Academy of Sleep Medicine Task Force on Respiratory Scoring reviewed the evidence that addresses: the validity of specific sensors in detecting airflow, tidal volume, oxyhemoglobin saturation, and CO2; the reliability of specific scoring approaches for quantifying sleep related breathing disorders (SRBD); and the validity of using various definitions of the apnea hypopnea index (AHI) as assessed by the strength and consistency of associations with several comorbidities (hypertension, cardiovascular disease, sleepiness, impaired quality of life, and accidents). The evidence was based on a literature search of relevant articles published through December 2004, which resulted in identifying and extracting data from 182 articles, which were graded using standardized approaches. Diverse physiological sensors have been utilized to quantify airflow limitation in patients with suspected SRBD. Although thermistry appears appropriate for identifying apneas, the available evidence did not indicate it provides valid quantification of airflow reduction. The emerging evidence evaluating the accuracy of signal detection against the gold standard measurements (e.g., pneumotachography) suggested the superiority of inductance plethysmography and nasal pressure transducers for detection of hypopneas, with some evidence that recordings from a nasal pressure transducer may better approximate flow/volume than uncalibrated inductance plethysmography. However, since the nasal pressure transducer has only recently been incorporated into large-scale studies, there are as of yet few data that address the predictive value of transducer-identified events relative to clinical or physiological outcomes. Very few studies directly compared the validity of alternative approaches for defining the duration, amplitude change, and use of corroborative data from desaturation or arousal for defining hypopneas. Many observational studies utilizing various designs and approaches for event detection have shown significant associations between measures of SRBD and health outcomes. Data from the 2 largest sleep cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort, both used definitions of hypopneas based on "discernible" reductions of inductance plethysmography signals with associated desaturation and showed that the derived AHIs using these hypopnea definitions correlated with various indices of morbidity. However, it is not clear whether alternative definitions would provide comparable if not better prediction, or whether optimal approaches for event identification would vary for different outcomes. Despite these limitations, forming a consensus on optimal approaches for recording and measuring respiratory events is an important step toward generating data from different clinical or research laboratories that can be compared. However, additional research is needed, including direct comparisons of alternative measuring approaches for predicting clinical outcomes, with a need to address these issues in large samples across the age spectrum and with inclusion of promising new technology.

Abstract: Our primary hypothesis was that the acute ventilatory response to carbon dioxide in the presence of sustained hypoxia {VRCO2 (hypoxia)} or hyperoxia {VRCO2 (hyperoxia)} would increase in subjects with obstructive sleep apnea (OSA) after exposure to episodic hypoxia. Secondarily, we hypothesized that chronic (i.e. years) exposure to episodic hypoxia, a hallmark of OSA, would facilitate persistent augmentation of respiratory activity (i.e. long-term facilitation) after acute (i.e. minutes) exposure to episodic hypoxia. Nine healthy males with OSA that were healthy otherwise completed a series of rebreathing trials before and after exposure to eight 4 min episodes of hypoxia. On a separate occasion, the rebreathing trials were repeated before and after exposure to atmospheric air for a duration equivalent to the episodic hypoxia protocol (i.e. sham episodic hypoxia). During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (P(ET)CO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen gas mixture (140 Torr). During the trials, P(ET)CO2 increased while the selected level of oxygen was maintained. The point at which ventilation began to rise in a linear fashion as P(ET)CO2 increased was the ventilatory threshold. The ventilatory response below and above the threshold was determined. The results showed that the VRCO2 (hypoxia) and the VRCO2 (hyperoxia) was increased after exposure to episodic hypoxia {VRCO2 (hypoxia): 7.9 +/- 1.3 versus 10.5 +/- 1.3, VRCO2 (hyperoxia): 5.9 +/- 1.1 versus 6.7 +/- 1.1 L/min/Torr}. However, only the increase in the VRCO2 (hypoxia) after episodic hypoxia was greater than the increase measured after exposure to sham episodic hypoxia. Long-term facilitation of ventilation, tidal volume and breathing frequency was not evident after episodic hypoxia. We conclude that the VRCO2 (hypoxia) is enhanced after exposure to acute episodic hypoxia and that enhancement of the VRCO2 (hypoxia) occurs even though long-term facilitation is not evident.

Abstract: We hypothesized that long-term facilitation (LTF) of minute ventilation and peak genioglossus muscle activity manifests itself in awake healthy humans when carbon dioxide is sustained at elevated levels. Eleven subjects completed two trials. During trial 1, baseline carbon dioxide levels were maintained during and after exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven subjects were exposed to sustained elevated levels of carbon dioxide in the absence of episodic hypoxia, which served as a control experiment. Minute ventilation was measured during trial 1, trial 2, and the control experiment. Peak genioglossus muscle activity was measured during trial 2. Minute ventilation during the recovery period of trial 1 was similar to baseline (9.3 +/- 0.5 vs. 9.2 +/- 0.7 l/min). Likewise, minute ventilation remained unchanged during the control experiment (beginning vs. end of control experiment, 14.4 +/- 1.7 vs. 14.7 +/- 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle activity during the recovery period of trial 2 was greater than baseline (minute ventilation: 28.4 +/- 1.7 vs. 19.6 +/- 1.0 l/min, P < 0.001; peak genioglossus activity: 1.6 +/- 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and peak genioglossus muscle activity and that LTF is only evident in awake humans in the presence of sustained elevated levels of carbon dioxide.

Abstract: Previously, we demonstrated that the respiratory and motor systems responded differently following consecutive lifts of an object whose weight could be altered (lighter or heavier) without changing the object's visual properties. When the weight of the object was altered in a manner unpredictable to the subject, the motor system response reflected the previous weight of the object (light or heavy) while the respiratory system reflected responses seen when lifting the heavier object regardless of whether a lighter or heavier object was lifted previously. It is possible that the default pattern of the respiratory system was due to a lack of visual size cues, which are known to have robust affects on grasp control. To test this hypothesis, 14 seated subjects performed self-initiated alternating lifts with objects whose size and weight covaried such that the weight of the upcoming lift was known despite the weight of the object previously lifted. Following both consecutive and alternating trials, the load force was scaled to the weight of the object (e.g., the heavier the object the larger the force) while the volume was scaled only following the consecutive trials. This suggests that the load forces were developed entirely based on visual information while lung volume was not. In addition, we suggest that following the consecutive trials, the volume increased as the object's weight increased in an effort to assist with trunk stabilization by indirectly increasing intra-abdominal pressure.

Abstract: BACKGROUND: We hypothesized that sympathetic nervous system activity (SNSA) is increased and parasympathetic nervous system activity (PNSA) is decreased during non-rapid eye movement (NREM) sleep in non-apneic, otherwise healthy, snoring individuals compared to control. Moreover, we hypothesized that these alterations in snoring individuals would be more evident during non-snoring than snoring when compared to control. METHODS: To test these hypotheses, heart rate variability was used to measure PNSA and SNSA in 11 normotensive non-apneic snorers and 12 control subjects before and 7-days after adapting to nasal continuous positive airway pressure (nCPAP). RESULTS: Our results showed that SNSA was increased and PNSA was decreased in non-apneic snorers during NREM compared to control. However, these changes were only evident during the study in which snoring was eliminated with nCPAP. Conversely, during periods of snoring SNSA and PNSA were similar to measures obtained from the control group. Additionally, within the control group, SNSA and PNSA did not vary before and after nCPAP application. CONCLUSION: Our findings suggest that long-lasting alterations in autonomic function may exist in snoring subjects that are otherwise healthy. Moreover, we speculate that because of competing inputs (i.e. inhibitory versus excitatory inputs) to the autonomic nervous system during snoring, the full impact of snoring on autonomic function is most evident during non-snoring periods.

Abstract: We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (Pet(CO(2))) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, Pet(CO(2)) increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as Pet(CO(2)) increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, Pet(CO(2)) levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.

Abstract: We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 +/- 0.82 vs. women, 4.70 +/- 0.77 l x min(-1) x Torr(-1); 150 Torr: men, 4.33 +/- 1.15 vs. women, 3.21 +/- 0.58 l x min(-1) x Torr(-1)). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 +/- 1.40 vs. women, 5.97 +/- 0.71 l x min(-1) x Torr(-1); 150 Torr: men, 5.73 +/- 0.81 vs. women, 3.83 +/- 0.56 l x min(-1) x Torr(-1)). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

Abstract: HYPOTHESIS: We hypothesized that baroreflex sensitivity is decreased during wakefulness and non-rapid eye movement sleep in normotensive, nonapneic snorers who are otherwise healthy. Moreover, we hypothesized that nocturnal alterations in baroreflex sensitivity are abolished during the application of nasal continuous positive airway pressure (nCPAP). DESIGN: The sequencing technique was used to measure baroreflex sensitivity in 16 normotensive nonapneic snorers and 16 control subjects matched for age, height, weight, gender, and race. Subsequently, baroreflex sensitivity was measured in 12 of 16 snorers and 14 of 16 control subjects during the application of nCPAP. RESULTS: Mean (+/- SE) baroreflex sensitivity was reduced during sleep in the nonapneic snoring group (wakefulness, 20.99 +/- 1.46 ms/mm Hg; sleep, 15.85 +/- 1.49 ms/mm Hg), but not in the control group (wakefulness, 21.82 +/- 2.48 ms/mm Hg; sleep, 23.54 +/- 2.18 ms/mm Hg). This reduction was abolished by the application of nCPAP in the snoring group (before nCPAP therapy, 16.30 +/- 2.17 ms/mm Hg; during nCPAP therapy, 20.63 +/- 2.40 ms/mm Hg). The application of nCPAP did not alter baroreflex sensitivity in the control group (before nCPAP therapy, 23.54 +/- 2.18 ms/mm Hg; during nCPAP therapy, 22.56 +/- 1.73 ms/mm Hg). BP was not significantly different between the snoring and control groups either before or during nCPAP application. CONCLUSIONS: Our findings suggest that nocturnal alterations in baroreflex sensitivity may exist in nonapneic snoring subjects prior to alterations in other cardiovascular variables.

Abstract: This investigation was designed to determine if suppression of testosterone alters the ventilatory response to carbon dioxide in the presence of high and low levels of oxygen. Eleven healthy male subjects completed a series of rebreathing trials during wakefulness, before and after treatment with a long-acting gonadotropin-releasing hormone agonist. Five subjects also completed studies during non-rapid eye movement (NREM) sleep. During wakefulness, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (P(ET,CO2)) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen (140 Torr) gas mixture. During each trial P(ET,CO2) increased while oxygen was maintained at a constant level. The threshold of the ventilatory response to carbon dioxide was considered to be the point at which minute ventilation began to rise in a linear fashion as P(ET,CO2) increased. The slope of the ventilatory response above the threshold was used as a measure of sensitivity to carbon dioxide. During NREM sleep, hypocapnia was induced via nasal mechanical ventilation. Several trials were completed until the cessation of mechanical ventilation resulted in a central apnoea which demarcated the threshold of the ventilatory response to carbon dioxide. In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 +/- 0.77 versus 39.40 +/- 0.83 Torr; P = 0.01) and high (46.32 +/- 0.56 versus 44.78 +/- 0.83 Torr; P = 0.01) oxygen levels. An increase in sensitivity (4.82 +/- 0.61 versus 7.17 +/- 1.20 l min(-1) Torr(-1); P = 0.02) was also observed during rebreathing in the presence of high but not low oxygen levels. The increase in sensitivity was accompanied by an increase in carbon dioxide production. The findings observed during NREM sleep were similar to those observed during wakefulness, since the P(ET,CO2) that demarcated the threshold was decreased after leuprolide treatment (42.1 +/- 0.6 versus 39.6 +/- 0.6 Torr; P = 0.002). Additionally, the decrease in P(ET,CO2) required to induce an apnoea was greater after treatment with leuprolide (2.56 +/- 0.25 versus 4.06 +/- 0.29 Torr; P = 0.004). We conclude that suppression of testosterone decreases the threshold of the ventilatory response to carbon dioxide during both wakefulness and sleep.

Abstract: We examined the presence of anticipatory control and the resulting interactions of the respiratory and motor systems during discrete object manipulation. In response to an auditory signal, subjects reached forward, grasped, and lifted an instrumented object weighing 150 or 1000 g while the breathing pattern, fingertip forces, and movements were measured. Following every block of five lifts, the object was removed from sight and replaced with the same or an alternate mass. Thus, the object's weight was predictable during the last lift of each block and unpredictable during the first lift after the transition. When the object's weight was predictable, the force application was faster and inspiratory duration and the tidal volume were reduced for the breath associated with the lift for 1000-g compared to 150-g lifts. Following the transition, when the object's weight was unpredictable, the force application reflected the weight of the object during the previous lift while the respiratory output, regardless of the preceding weight, resembled that used for 1000-g lifts. Additionally, inspiratory duration was significantly correlated with the reach duration in three of the four unpredictable lifting conditions. We conclude that these system-specific anticipatory alterations may arise from a common internal representation that was formed through past manipulatory weight experience.

Abstract: We hypothesized that patients with obstructive sleep apnea (OSA) have a different awake ventilatory response to carbon dioxide above and below eupnea compared with normal. Eight male subjects with OSA and control subjects matched for gender, race, age, height and weight voluntarily hyperventilated during wakefulness to reduce the partial pressure of carbon dioxide (PET(CO2)) below 25 mmHg. Subjects were then switched into a rebreathing bag containing a normocapnic (42 mmHg) hypoxic [partial pressure of end tidal oxygen (PET(O2))=50 mmHg (H50)] or hyperoxic [PET(O2)=140 mmHg (H140)] gas mixture. During the trial PET(CO2) increased while PET(O2) was maintained at a constant level. The point at which ventilation and PET(CO2) increased linearly was considered to be the carbon dioxide ventilatory recruitment threshold (VRT(CO2)). Measurements of ventilation and its components (i.e. tidal volume and breathing frequency) were made below this threshold and the slope of the minute ventilation; tidal volume or breathing frequency response above the threshold was determined. Four trials for a given oxygen level were completed. The PET(CO2) that demarcated the VRT(CO2) was increased (H(50)=43.43+/-0.92 vs. 41.05+/-0.67; H(140)=47.65+/-0.80 vs. 45.28+/-0.75), as were measures of ventilation below the threshold (H(50)=18.50+/-2.11 vs. 13.44+/-1.43; H(140)=19.66+/-2.71 vs. 10.83+/-1.24) in the OSA subjects compared with control. In contrast the OSA and control subjects did not respond differently to changes in PET(CO2) above the threshold. We conclude that the PET(CO2) that delineates the VRT(CO2) and ventilation below this threshold is elevated in subjects with OSA.

Abstract: We tested the hypothesis that abdominal muscles are active during the expiratory phase of the respiratory cycle during exercise. Electromyographic (EMG) activities of external oblique and rectus abdominis muscles were recorded during incremental exercise to exhaustion and during 30 min of constant work rate exercise at an intensity of 85 % of the peak oxygen consumption rate (V(O(2))). High amplitude intramuscular EMG activities of both abdominal muscles could be evoked with postural manoeuvres in all subjects. During cycling, respiratory-related activity of the external obliques was evoked in four of seven subjects, whereas rectus abdominis activity was observed in six of the seven subjects. We measured only the activity that was confined exclusively to the expiratory phase of the respiratory cycle. Expiratory activity of both muscles increased with exercise intensity, although peak values averaged only 10-20 or 20-40 % of the peak activity (obtained during maximal, voluntary expiratory efforts) for the external oblique and rectus abdominis muscles, respectively. To estimate how much of the recorded abdominal muscle activity was supporting leg movements during exercise, we compared the activity at the very end of incremental exercise to that recorded during the first five respiratory cycles after the abrupt cessation of exercise, when ventilation was still very high. Although external oblique activity was reduced after exercise stopped, clear expiratory activity remained. Rectus abdominis activity remained high after exercise cessation, showing a gradual decline that approximated the decline in ventilation. During constant work rate exercise, EMG activities increased to 40-50 and 5-10 % of peak in rectus and external oblique muscles, respectively, and then plateaued for the remainder of the bout in spite of a continual upward drift in (V(O(2))) and pulmonary ventilation. Linear regression analysis showed that the rise in respiratory-related expiratory muscle activity during progressive intensity exercise was significantly correlated with ventilation, although weakly. In constant work rate exercise, expiratory EMG activities increased, but the changes were highly variable and did not change as a function of exercise time, even though ventilation drifted significantly with time. These experiments suggest that abdominal muscles play a role in regulating the ventilatory response to progressive intensity bicycle exercise, although some of the observed activity may support postural adjustments or limb movements. The contribution of abdominal muscles to ventilation during constant work rate exercise is variable, and expiratory activity does not 'drift' significantly with time.

Abstract: STUDY OBJECTIVES: Obstructive sleep apnea (OSA) appears to be an independent risk factor for diurnal systemic hypertension, but the specific biologic markers for this association have not been well established. Increased arterial stiffness is an important measure of increased left ventricular load and a predictor of cardiovascular morbidity and may precede the onset of systemic hypertension in humans. However, arterial stiffness has not been measured in association with obstructive apneas in patients with OSA, nor related to systemic blood pressure (BP) activity in this setting. Our objective was to test the hypothesis that arterial stiffness may be utilized as a sensitive measure of arterial vasomotor perturbation during obstructive events in patients with OSA, by demonstrating that (1) arterial stiffness increases acutely in association with obstructive apnea and hypopnea, and that (2) such increased stiffness may occur in the absence of acute BP increase. DESIGN: Prospective, cross-sectional. SETTING: A tertiary-care university-based sleep and ventilatory disorders center. PATIENTS: Forty-four normo- and hypertensive adult patients (11 women, 33 men) with polysomnographically diagnosed moderate to severe OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Beat-to-beat BP was recorded from the radial artery by applanation tonometry during nocturnal polysomnography. Arterial augmentation index (AAI), a measure of arterial stiffness, was calculated as the ratio of augmented systolic BP (SBP) to pulse pressure and expressed as a percentage for the following conditions: awake, the first 10 ("early apnea") and last 10 ("late apnea") cardiac cycles of obstructive events, and the first 15 cardiac cycles following apnea termination ("post apnea"). Mean AAI (+/-SD) for the group was significantly increased during NREM sleep from early apnea to late apnea (12.02 +/- 2.70% vs 13.35 +/- 3.54%, p<0.05, ANOVA). During REM (analyzed in 20 patients), MI again significantly increased from early apnea to late apnea (11.75 +/- 2.81% vs 13.43 +/- 4.97%). Conversely, neither mean SBP nor mean arterial BP was significantly changed from early apnea to late apnea in NREM (SBP 130 +/- 14 mmHg vs 129 +/- 14 mmHg) or REM (SBP 128 +/- 22 mmHg vs 127 +/- 21 mmHg). CONCLUSIONS: Arterial stiffness increases acutely during obstructive apneas in both NREM and REM sleep, in the absence of measurable BP change. These data suggest that arterial stiffness may be a sensitive measure of acute arterial vasomotor perturbation in this setting and may have implications concerning cardiovascular sequelae in patients with OSA.

Abstract: STUDY OBJECTIVES: The purpose of the present investigation was to examine the effect of lung volume and inspiration of 100% oxygen on blood pressure and R-R interval responses during the Valsalva maneuver. DESIGN AND PARTICIPANTS: Fourteen healthy subjects completed eight Valsalva maneuvers. Four of the maneuvers were completed after inspiring to total lung capacity while the remaining maneuvers were completed at end-expiratory lung volume. Two maneuvers completed at a given lung volume were performed under hyperoxic conditions while the remaining maneuvers were completed under normoxic conditions. RESULTS: Overall, a significant increase in blood pressure and decrease in R-R interval occurred throughout phases I-IV of the Valsalva maneuvers that were initiated from end-expiratory lung volume as compared to total lung capacity. These changes were accompanied by a concomitant increase in baroreflex sensitivity during phase IV. Furthermore, independent of lung volume the baroreflex response was attenuated under hyperoxic conditions. CONCLUSIONS: We conclude that the lung volume that exists prior to the onset of the maneuver alters the blood pressure and R-R interval response during phases I-IV of the Valsalva maneuver. Furthermore, we suggest that these responses are mediated in part by changes in chemoreceptor activity since the baroreflex was reset and the sensitivity was reduced under hyperoxic conditions. Given these findings, we recommend that lung volume be controlled when patients are completing a Valsalva maneuver to obtain reliable and reproducible measures of blood pressure, R-R interval duration and baroreflex sensitivity.

Abstract: STUDY OBJECTIVES: We hypothesized that blood pressure (BP) is less during snoring as compared to periods of non-snoring in non-apneic individuals. Furthermore, we hypothesized that this reduction may be accompanied by a simultaneous decrease in sympathetic (SNSA) and parasympathetic (PNSA) nervous system activity and an increase in heart rate (HR). DESIGN: N/A. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. MEASUREMENTS: The variables mentioned above in addition to breathing frequency were measured in 9 subjects during NREM sleep. In addition, the lowest systolic (SBP) and diastolic blood pressure (DBP) during inspiration and the highest SBP and DBP during expiration was determined breath-by-breath from segments selected from each NREM cycle. Heart rate variability was used as a marker of autonomic nervous system activity. RESULTS: Our results showed that BP during snoring decreased compared to non-snoring and the breath-by-breath BP analysis suggested that this difference may have been mediated by changes in intrathoracic pressure. In conjunction with the decrease in BP, SNSA decreased and HR increased however PNSA remained constant. Thus, a decrease in PNSA was likely not the primary mechanism responsible for the HR response. CONCLUSIONS: We conclude that BP responses and SNSA during snoring are similar to that reported previously in non-snoring individuals. However, the causal mechanisms maybe different and manifested in other measures such as HR. Thus, nocturnal cardiovascular and autonomic function maybe uniquely different in non-apneic snoring individuals.

Abstract: In this study of adult and neonatal rats, we used cross-correlation analysis to detect synchronous neuronal events in hypoglossal and phrenic nerves to infer synaptic connections. We found evidence for the common excitation of medial and lateral hypoglossal motoneurones in 12 anaesthetized adult rats but not in 6 in vitro brainstem-spinal cord preparations. We did not find evidence for the common activation of phrenic and hypoglossal motoneurones in 23 adult and 10 neonatal rat preparations. We confirmed this negative result by demonstrating that 26 medullary inspiratory neurones activating phrenic motoneurones did not activate hypoglossal motoneurones in 23 adult decerebrate rats (except in one case). We also found that 15 Bötzinger expiratory neurones inhibiting phrenic motoneurones did not inhibit hypoglossal motoneurones. We conclude that: (1) motoneurones of the medial and lateral hypoglossal nerve branches receive inspiratory drive from a common premotor population in adult rats, but in neonatal rats adjacent nerve rootlets do not; (2) in both adult and neonatal rats phrenic premotor neurones do not monosynaptically excite hypoglossal motoneurones; (3) Bötzinger expiratory neurones that inhibit phrenic motoneurones do not inhibit hypoglossal motoneurones. We therefore suggest that the respiratory control of hypoglossal motoneurones is separate from that of phrenic motoneurones.

Abstract: This investigation was designed to examine the relationship between breathing and prehension movements during object manipulation. Seated subjects (n=12) wore a facemask that was attached to a pneumotachometer which measured airflow. Initially, subjects completed baseline trials that were preceded and followed by an object lift. Subsequently, in response to an auditory signal the subjects reached forward, grasped and lifted an instrumented object that weighed either 150 g or 1000 g while their fingertip forces and movements were measured. The auditory signal was triggered by airflow in response to four experimental conditions (1) expiratory onset (2) inspiratory onset (3) mid-inspiration and (4) mid-expiration. Five trials for each of the four conditions were completed with each weight. The results revealed that inspiratory time was longer under baseline conditions after the subjects lifted the 150 g object as compared to the 1000 g object. In addition, the response latency and reach duration were significantly slower for the 150 g object compared to the 1000 g object during the experimental trials. These temporal measures were significantly correlated to inspiratory time for three of the four experimental conditions but no significant relationship with expiratory time was found. Lastly, lifting of the object occurred during expiration during most experimental conditions. We conclude that an adaptive process is formulated for both the motor and respiratory system in response to changes in motor output and/or sensory inputs associated with object manipulation, that might manifest itself in the pattern of breathing subsequent to removal of these stimuli. Furthermore, we suggest that motor inputs associated with the initiation of object manipulation interact with the control of respiratory timing so that the motor and respiratory systems are coupled. We speculate that this relationship may ensure that some motor tasks are performed during expiration to take advantage of changes in intrathoracic pressure that assist in postural maintenance during completion of the task.

Abstract: The primary purpose of this study was to measure baroreceptor sensitivity (BS) during wakefulness and non-rapid eye movement (NREM) sleep in non-apneic snoring individuals. To achieve this purpose continuous and simultaneous measurements of snoring, oxygen saturation, sleep stages, arterial blood pressure and heart rate were obtained from seven non-apneic snoring subjects. After obtaining these measures, a computer program was employed to detect concomitant increases or decreases in systolic blood pressure and R-R interval duration during sequences of three or more consecutive beats that occurred during stage II and slow wave sleep (SWS). The values recorded from a given sequence were plotted and the slope of the regression line fit to the data was used as a measure of BS. The results showed that mean arterial pressure and heart rate during stage II and SWS of NREM sleep were not significantly different from wakefulness. In contrast, the BS measured during NREM sleep was significantly lower than values recorded during wakefulness. In addition, linear regression analysis showed that an inverse and significant correlation existed between snoring frequency and the decrease in BS during sleep. We conclude that the decrease in blood pressure and heart rate normally observed during NREM sleep in healthy non-snoring individuals is attenuated or abolished in non-apneic snoring individuals and that these cardiovascular alterations may be partially mediated by a decrease in BS.

Abstract: It is well established that the genioglossus muscle (tongue protrudor) has a role in protecting or enhancing upper airway patency in individuals with obstructive sleep apnea. However, no investigation completed to date has addressed the role of the styloglossus and hyoglossus muscles (tongue retractors) in maintaining upper airway patency in humans. As a first step toward this goal, the present investigation was designed to examine the response of human tongue protrudor and retractor muscles during a breathhold maneuver and in steady-state hypoxic hypercapnia. The results showed that the protrudor and retractor muscles were coactivated under both conditions. Measurements of onset time of electromyographic activity during steady-state hypoxic hypercapnia revealed that phasic protrudor and retractor activity was initiated immediately before or during the early part of inspiration. We conclude that the tongue protrudor and retractor muscles are coactivated in response to hypoxia and hypercapnia, and that the tongue retractors may have a significant role in protecting upper airway patency during both apnea and hyperpnea.

Abstract: The technique of intramuscular microstimulation was used to activate facial nerve fibers while acquiring simultaneous twitch force measurements to measure the contractile properties and force-frequency responses of human nasal dilator (ND) motor units. Twitch force amplitude (TF), contraction time (CT), half-relaxation time (HRT), and the maximal rate of rise of force normalized to the peak force (maximum contraction rate, MCR) were recorded from 98 ND motor units in 37 subjects. The average CT, HRT, MCR, and TF were 47.9 +/- 1.8 ms, 42.6 +/- 2.1 ms, 28.6 +/- 1.8 s-1, and 1.06 +/- 0.1 mN, respectively. Neither CT nor HRT were significantly correlated with TF. The average CT and HRT were similar to values recorded for small muscles of the hand but were faster than the values recorded from human toe extensor motor units. However the lack of an association between twitch force and CT or HRT was similar to the findings obtained for both human hand and foot muscles. Force-frequency curves were recorded from eight ND motor units. The force produced by the eight motor units was recorded in response to stimuli delivered at 1, 5, 10, 15, 20, 25, 30, 35, and 40 Hz to assess force-frequency relationships. The mean twitch force of the eight motor units was 0.91 +/- 0.3 mN and the average tetanic force was 8.1 +/- 1.8 mN. Therefore the average twitch force was equal to 12.7% of the tetanic force. Fifty percent of the unit tetanic force was achieved at an average frequency of 16. 4 +/- 1.7 Hz, which is greater than the value recorded for human toe extensor motor units (9.6 Hz). Thus the force produced by the ND motor units was more sensitive to changes in discharge frequency over the range of approximately 10-30 Hz and less sensitive to changes in the range of 0-10 Hz because of their fast contractile properties. The mean slope of the regression lines that were fit to the steep portion of each force-frequency curve was 5.15 +/- 0.5% change in force/Hz. This value was greater than the slope measured for human toe extensor muscles (4.2% change in force/Hz). These observations suggest that force gradation by ND motor units is more sensitive to changes in stimulation frequency than human toe extensor motor units. We conclude that most ND motor units have fast contractile properties and that rate coding may play a significant role in the gradation of force produced by the ND muscle. Furthermore, the findings of this investigation have demonstrated that contractile speed and TF in a human facial muscle are not correlated. This supports previous findings obtained from human hand and foot muscles and suggests that there may be a fundamental difference in the contractile speed-twitch force relationship between many human muscles and most muscles of other mammals.

Abstract: 1. Our primary purpose was to test the hypothesis that the tongue protrudor (genioglossus, GG) and retractor (styloglossus, SG and hyoglossus, HG) muscles are co-activated when respiratory drive increases, and that co-activation will cause retraction of the tongue. This was addressed by performing two series of experiments using a supine, anaesthetized, tracheotomized rat in which tongue muscle force and the neural drive to the protrudor and retractor muscles could be measured during spontaneous breathing. In the first series of experiments, respiratory drive was increased progressively by occluding the tracheal cannula for thirty respiratory cycles; in the second series of experiments, the animals were subjected to hyperoxic hypercapnia and poikilocapnic hypoxia. 2. Airway occlusion for thirty breaths caused progressive, quantitatively similar increases in efferent motor nerve activity to protrudor and retractor tongue muscles. Net tongue muscle force was always consistent with tongue retraction during occlusion, and peak force rose in parallel with the neural activites. When airway occlusion was repeated following section of the lateral XIIth nerve branch (denervation of retractor muscles) the tongue either protruded (15/21 animals; 10 +/- 2 mN at the 30th occluded breath) or retracted weakly (6/21 animals; 6 +/- 2 mN at 30th occluded breath). 3. To ensure that our findings were not the result of damage to the muscle nerves, occlusion experiments were also done in eight animals in which GG EMG activity was recorded instead of nerve activities. Changes in peak integrated GG electryomyogram (EMG) activity and peak retraction force during occlusion were highly correlated (r2 = 0.86, slope = 1.05). 4. In separate experiments in fourteen rats, we found that hyperoxic hypercapnia and poikilocapnic hypoxia also result in parallel increases in the respiratory-related EMG activity of the GG and HG muscles. Also, as in the occlusion experiments, augmentations of protrudor and retractor muscle EMG activities were associated with parallel changes in tongue retraction force. 5. These studies in anaesthetized rats demonstrate that tracheal occlusion and independent stimulation of central or peripheral chemoreceptors results in inspiratory-related co-activation of the protrudor and retractor muscles, and proportional changes in tongue retraction force. These observations also demonstrate that recording GG EMG activity in isolation could lead to erroneous conclusions about respiratory-related movements of the tongue.

Abstract: The primary purpose of the present investigation was to determine whether long-term facilitation (LTF) of upper airway muscle activities occurs in vagotomized and vagally intact cats. Tidal volume and diaphragm, genioglossus, and nasal dilator muscle activities were recorded before, during, and after one carotid sinus nerve was stimulated five times with 2-min trains of constant current. Sixty minutes after stimulation, nasal dilator and genioglossus muscle activities were significantly greater than control in the vagotomized cats but not in the vagally intact cats. Tidal volume recorded from the vagotomized and vagally intact cats was significantly greater than control during the poststimulation period. In contrast, diaphragm activities were not significantly elevated in the poststimulation period in either group of animals. We conclude that 1) LTF of genioglossus and nasal dilator muscle activities can be evoked in vagotomized cats; 2) vagal mechanisms inhibit LTF in upper airway muscles; and 3) LTF can be evoked in accessory inspiratory muscles because LTF of inspired tidal volume was greater than LTF of diaphragm activity.

Abstract: These experiments were designed to examine the behavior of external oblique motor units in spontaneously breathing cats during hypoxia and to estimate the contribution of recruitment and rate coding to changes in the integrated external oblique electromyogram (iEMG). Motor unit activities in the external oblique muscle were identified while the cats expired against a positive end-expiratory pressure (PEEP) of 1-2.5 cmH2O. After localization of unit activity, PEEP was removed, and recordings were made continuously for 3-4 min during hyperoxia, normoxia, and hypoxia. A total of 35 single motor unit activities were recorded from 10 cats. At each level of fractional concentration of end-tidal O2, the motor unit activity was characterized by an abrupt increase in mean discharge frequency, at approximately 30% of expiratory time, which then continued to increase gradually or remained constant before declining abruptly at the end of expiration. The transition from hyperoxia to normoxia and hypoxia was accompanied by an increase in the number of active motor units (16 of 35, 20 of 35, and 29 of 35, respectively) and by an increase in the mean discharge frequency of those units active during hyperoxia. The changes in motor unit activity recorded during hypoxia were accompanied by a significant increase in the average peak amplitude of the abdominal iEMG. Linear regression analysis revealed that motor unit rate coding was responsible for close to 60% of the increase in peak iEMG amplitude. The changes in abdominal motor unit activity and the external oblique iEMG that occurred during hypoxia were abolished if the arterial PCO2 was allowed to fall. We conclude that external oblique motor units are activated during the latter two-thirds of expiration and that rate coding and recruitment contribute almost equally to the increase in expiratory muscle activity that occurs with hypoxia. In addition, the excitation of abdominal motor units during hypoxia is critically dependent on changes in CO2 and/or tidal volume.

Abstract: During the past 100 years many experimental investigations have been carried out in an attempt to determine the control mechanisms responsible for generating the respiratory responses observed during incremental and constant-load exercise tests. As a result of these investigations a number of different and contradictory control mechanisms have been proposed to be the sole mediators of exercise hyperpnea. However, it is now becoming evident that none of the proposed mechanisms are solely responsible for eliciting the exercise respiratory response. The present-day challenge appears to be one of synthesizing the proposed mechanisms, in order to determine the role that each mechanism has in controlling ventilation during exercise. This review, which has been divided into three primary sections, has been designed to meet this challenge. The aim of the first section is to describe the changes in respiration that occur during constant-load and incremental exercise. The second section briefly introduces the reader to traditional and contemporary control mechanisms that might be responsible for eliciting at least a portion of the exercise ventilatory response during these types of exercise. The third section describes how the traditional and contemporary control mechanisms may interact in a complex fashion to produce the changes in breathing associated with constant-load exercise, and incorporates recent experimental evidence from our laboratory.

Abstract: These experiments examined the effect of metabolic acidosis, induced as a result of dynamic exercise, on ventilation, lactate concentration and electromyographic activity. Seven subjects performed two consecutive incremental exercise tests until volitional exhaustion was achieved. The two tests were identical and were separated by a 7-min period of light exercise. During the tests, ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood and electromyographic activity from the vastus lateralis was sampled. The results showed that the ventilation and electromyographic measurements followed a similar time course during both tests, although ventilation during the initial 6 min of the second test was significantly greater than the values recorded during the first test. In addition, throughout the first test lactate concentration increased with time, and pH, bicarbonate concentration and partial pressure of carbon dioxide decreased. In contrast, during the second test, lactate concentration decreased, and pH and bicarbonate concentration increased; during a period of time when ventilation and electromyographic activity were increasing. These findings have led us to conclude that changes in ventilation and electromyographic activity observed during incremental exercise are not related to changes in blood lactate concentration. It is suggested that such a conclusion supports the hypothesis that the changes in ventilation are mediated by an increase in neural activity originating from the subthalamic motor region or exercising limbs, induced in response to the need to progressively recruit fast twitch muscle fibres as exercise work rate is increased and as individual muscle fibres begin to fatigue.

Abstract: These experiments examined the changes in ventilation at the start and end of exercise. Six subjects walked on a treadmill at two work rates above and two below that corresponding to their first ventilatory thresholds, for three durations. The subjects also exercised at the lowest and highest work rates while inspiring oxygen-enriched air. The group mean results showed that the abrupt increases in ventilation at the start of exercises at work rates above that of the first ventilatory threshold were greater than those below, but did not vary with duration or work rate either above or below. The abrupt falls in ventilation at the end of the exercises were less than the increases at the start. At work rates above that of the first ventilatory threshold, increases in work rate and duration were found to reduce the abrupt falls. The time constants of exponential curves fitted to the post-exercise declines in ventilation increased with work rate, and also with duration for work rates above that of the first ventilatory threshold. Finally, breathing oxygen enriched air did not alter any of these variables. These findings were interpreted as showing that the fast neural exercise drive is enhanced at work rates above that of the first ventilatory threshold, and becomes progressively less as exercise continues, a process exaggerated at higher work rates. In addition, the time course of the decline in ventilation following exercise, although altered by work rate and duration, was independent of the level of oxygenation.

Abstract: These experiments examined the effect of hypoxia and hyperoxia on ventilation, lactate concentration and electromyographic activity during an incremental exercise test in order to determine if coincident chances in ventilation and electromyographic activity occur during an incremental exercise test, despite an enhancement or reduction of peripheral chemoreceptor activity. In addition, these experiments were completed to determine if electromyographic activity and ventilation are enhanced or reduced in response to the inspiration of oxygen-depleted and oxygen-enriched air, respectively. Seven subjects performed three incremental exercise tests, until volitional exhaustion was achieved, while inspiring air with a fractional concentration of oxygen of either 66%, 21% or 17%. In addition, another single subject completed two tests while inspiring air with a fractional concentration of either 17% or 21%. During the tests, ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood and the electromyographic activity from the vastus lateralis were sampled. From these values ventilation, electromyographic and lactate thresholds were detected during normoxia, hypoxia and hyperoxia. The results showed that although ventilation and lactate concentration were significantly less during hyperoxia as compared to normoxia or hypoxia, the carbon dioxide production values were not significantly different between the normoxic, hypoxic and hyperoxic conditions. For a particular condition, the time, carbon dioxide production and oxygen consumption values that corresponded to the ventilation and electromyographic thresholds were not significantly different, but the values corresponding to the lactate threshold were significantly less than those for the electromyographic and ventilation thresholds. Comparisons between the three conditions showed that the time, carbon dioxide production and oxygen consumption values corresponding to each of these thresholds were not significantly difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: This study was designed to test a hypothesis that patients with sleep apnea have higher blood pressure in the morning, following a night spent in apnea and hypoxemia, than in the evening. To accomplish this, we prospectively studied a set of 611 patients referred to our clinic because of suspicion of sleep apnea. All patients had full nocturnal polysomnography, including measurement of snoring. Blood pressure was measured in the evening, prior to onset of sleep, and in the morning, immediately on awakening. We found that patients without apnea and hypoxemia had lower blood pressure in the morning compared with the evening value, while patients with severe sleep apnea and hypoxemia had higher blood pressure in the morning; these evening-to-morning blood pressure differences, although statistically significant, were small, typically 1 to 4 mm Hg. Morning blood pressures were higher in patients with sleep apnea and hypoxemia than in nonapneic normoxic patients. However, this difference disappeared after the groups were matched for age and body mass index. We conclude that (1) patients with sleep apnea and nocturnal hypoxemia lose the expected morning dip in arterial blood pressure, and (2) age and body mass index are more important correlates of blood pressure than apnea and nocturnal oxygen desaturation. We speculate that the loss of evening-to-morning drop in blood pressure, if present over a long period of time, may lead to sustained elevations in arterial blood pressure frequently observed in patients with sleep apnea.

Abstract: The purpose of this study was to examine the relationship between snoring and mean arterial blood pressure during sleep. This was accomplished by performing continuous, all-night, simultaneous measurements of snoring, oxygen saturation, sleep stages, and arterial blood pressure in a group of eight snorers and five nonsnoring control subjects. The results were analyzed to determine whether changes in mean arterial blood pressure during non-rapid-eye-movement (non-REM) sleep are different in snorers from those in nonsnorers and whether they are related to nocturnal hypoxemia. Both groups were similar with respect to their anthropometric parameters and sleep architecture. Oxygen saturations during different stages of non-REM sleep were similiar within each group. However, the analysis of variance revealed that among snorers mean arterial blood pressure increased slightly during slow-wave sleep, whereas the nonsnorers reduced their blood pressure by 17.4 +/- 3.7% compared with wakefulness values. We also performed multiple linear regression analysis for the entire group of 13 subjects using the change in mean arterial blood pressure relative to wakefulness as the dependent variable and snoring frequency and mean arterial oxygen saturation as the independent variables; the results demonstrated that only snoring frequency, and not oxygen saturation, correlated significantly with the change in mean arterial blood pressure. We conclude that snoring may influence variation of blood pressure during sleep, preventing the normally observed reduction of arterial blood pressure associated with slow-wave sleep.

Abstract: These experiments examined the effect of exercise intensity and duration on the magnitude of the abrupt change in ventilation at the start (VE,start) and end (VE,end) of exercise. Five subjects performed constant load treadmill exercise at 50% and 80% of their maximum oxygen consumption (VO2max) for 6 and 10 min while inspiring atmospheric air. The subjects also completed additional exercise tests at 80% VO2max for 10 min while inspiring an oxygen-enriched gas mixture. During each exercise trial ventilation was measured breath-by-breath. The VE,start and VE,end were determined by using non-linear curve-fitting techniques. The results showed that VE,start was greater at the start of the 80-% exercise tests compared to the 50-% tests and that VE,start at each level of exercise was greater than VE,end. The results also demonstrated that VE,end was inversely related to the intensity and duration of exercise. Furthermore, the VE,end was not altered subsequent to the inspiration of oxygen-enriched air. These findings have led us to postulate that the stimulus responsible for VE,start is reduced during exercise and that the degree of reduction is related to the intensity and duration of exercise. In addition, it was concluded that these changes might occur independently of peripheral chemoreceptor activity.

Abstract: The purpose of this study was to examine whether snoring adversely affects sleep architecture and sleep efficiency, and thus may account for the frequent complaints of daytime tiredness and fatigue expressed by heavy snorers. We recruited eight self-confessed heavy snorers and six self-confessed nonsnorers. All subjects had full nocturnal polysomnography, including continuous monitoring of snoring, which was quantified by counting the number of snores per hour of sleep (snoring index), the number of snores per minute of snoring time (snoring frequency), maximal and mean nocturnal sound intensity (dBmax and dBmean, respectively). We found that even the self-confessed nonsnorers snored lightly, with significantly smaller frequency and index than the heavy snorers. Sleep architecture was similar in both groups. Distribution of snoring among the sleep stages differed for light and heavy snorers: light snorers snored uniformly throughout all sleep stages, whereas heavy snorers tended to snore more during slow-wave and REM sleep. Snoring frequency and snoring index were similar during all sleep stages in light snorers, but they were higher during slow-wave sleep in heavy snorers. Wakefulness time after sleep onset and sleep efficiency correlated significantly with the snoring index. We conclude that although snoring does not affect sleep architecture in general, it influences sleep efficiency and wakefulness time after sleep onset; this may have an adverse effect on daytime function of heavy snorers.

Abstract: Arterial oxyhemoglobin saturation (SaO2) falls to a variable extent during sleep in patients with COPD. These nocturnal falls in SaO2 may contribute to the development of pulmonary hypertension, nocturnal cardiac arrhythmias, and death during sleep. In order to determine which physiologic factors measured during wakefulness might contribute to the development of nocturnal hypoxemia, we performed multiple stepwise linear regression analyses in 48 patients with stable COPD with mean and lowest nocturnal SaO2 as dependent variables. It was concluded that the two chief variables, measured while awake, which are associated with alterations in nocturnal oxygenation in patients with COPD are baseline awake SaO2 and PaCO2. Hypercapnia appears to be a risk factor for the development of nocturnal hypoxemia in patients who are normoxic while awake.

Abstract: These experiments examined possible inhibitory inputs to upper cervical inspiratory neurons from the expiratory neurons of the Botzinger complex. Eighty-one Botzinger neurons were tested with antidromic mapping for a projection to the C1 segment of the spinal cord; 44/81 (54%) were found to project, 27/79 (34%) contralaterally, 17/68 (25%) ipsilaterally, and 1/66 (2%) both contralaterally and ipsilaterally. Antidromic mapping in contralateral C1 demonstrated the presence of a collateral in 3/15 (20%) of the Botzinger neurons tested, while 3/9 (33%) had collateral arborizations in ipsilateral C1. The collaterals mapped were not localized to the region of the upper cervical inspiratory neurons. Microstimulation in C3 (12-17 microA, 0.2-ms duration) at locations which produced short-latency (2.7-3.5 ms) inhibition of phrenic nerve discharge resulted in the short latency (3.0 ms) inhibition of 1/27 (3.7%) upper cervical inspiratory neurons as demonstrated by cross-correlation. It was concluded that while some upper cervical inspiratory neurons may be inhibited during expiration by the Botzinger expiratory neurons, this connection is not a strong one.

Abstract: In the present study, we have undertaken a detailed analysis of the respiratory physiologic correlates of SaO2 during mild constant-load exercise in 38 patients with severe but stable COPD. Several respiratory physiologic variables that would be expected to influence exercise SaO2 were entered into a stepwise multiple linear regression analysis with mean exercise SaO2 as the dependent variable. Two variables (Dco and resting SaO2) were found to correlate strongly with mean exercise SaO2 (multiple r = 0.80; p less than 0.00001) and accounted for 65 percent of the variability among patients. The PaCO2 influenced resting SaO2 but had no independent influence on exercise SaO2. Subsequently, the model of mean exercise SaO2 derived in the present analysis was found to accurately predict mean exercise SaO2 in a group of 19 similar patients (r = 0.85; p less than 0.0001). While these findings do not establish a cause-and-effect relationship, they may provide clinicians with further insight as to which patients are likely to desaturate during exercise.