Auto-CPAP treatment in obstructive sleep apnea syndrome: a prospective randomized study during initiation of treatment

OBJECTIVE: The efficacy and acceptance of self-regulated continuous positive airway pressure (auto-CPAP) ventilation was compared with conventional CPAP administration in the treatment of patients with obstructive sleep apnoea. PATIENTS AND METHODS: Using a cross-over design, under polysomnographic monitoring in a sleep laboratory, 25 patients with obstructive sleep apnoea underwent conventional CPAP or auto-CPAP treatment. Using a questionnaire, patients gave their assessment of its acceptability and efficacy after each treatment session. RESULTS: The mean pressure during treatment was the same in the two groups (7.2 +/- 1.9 versus 7.1 +/- 1.9 mbar; no significant difference). Maximal pressure during auto-CPAP averaged 3.7 +/- 2.1 mbar higher than during conventional CPAP ventilation. The mean apnoea-hypopnoea index (AHI) during auto-CPAP, 4.4 +/- 4.3 mbar, during auto-CPAP was significantly higher than during conventional CPAP treatment (2.8 +/- 2.8 mbar; P = 0.044). In eight patients on auto-CPAP an AHI of 5 or less could not be reached, while an AHI of 5 or less was obtained in all but three patients under conventional CPAP. In a subgroup of 17 patients, in whom a reduction of AHI to at most 5 was achieved with both conventional and auto-CPAP, analysis of sleep pattern and of arousals was similar with the two forms of ventilation. Several patients reported that with auto-CPAP falling in sleep was more difficult and they slept less well. None of the patients preferred auto-CPAP. CONCLUSION: By means of the auto-CPAP neither a pressure reduction nor an improvement in compliance could be achieved. Therapeutic effectiveness was significantly less as with conventional CPAP therapy.     

Sleep bruxism is a disorder related to periodic arousals during sleep

There is evidence that sleep bruxism is an arousal-related phenomenon. In non-REM sleep, transient arousals recur at 20- to 40-second intervals and are organized according to a cyclic alternating pattern. Polysomnographic recordings from six subjects (two females and four males) affected by sleep bruxism (patients) and six healthy age-and gender-matched volunteers without complaints about sleep (controls) were analyzed to: (1) compare the sleep structure of bruxers with that of non-complaining subjects; and (2) investigate the relations between bruxism episodes and transient arousals. Patients and controls showed no significant differences in conventional sleep variables, but bruxers showed a significantly higher number of the transient arousals characterized by EEG desynchronization. Bruxism episodes were equally distributed between non-REM and REM sleep, but were more frequent in stages 1 and 2 (p < 0.0001) than in slow-wave sleep. The great majority of bruxism episodes detected in non-REM sleep (88%) were associated with the cyclic alternating pattern and always occurred during a transient arousal. Heart rate during the bruxism episodes (69.3+/-18.2) was significantly higher (p < 0.0001) than that during the pre-bruxing period (58.1+/-15.9). Almost 80% of all bruxism episodes were associated with jerks at the anterior tibial muscles. The framework of the cyclic alternating pattern offers a unified interpretation for sleep bruxism and arousal-related phenomena.     

In vivo 1H MRS of normal breast and breast tumors using a dedicated double breast coil

OBJECTIVE: To characterize sleep patterns of patients with juvenile rheumatoid arthritis (JRA). METHODS: Sixteen patients with JRA aged 12+/-4 years and 9 controls aged 11+/-3 years underwent a comprehensive evaluation by self-report questionnaire and formal all night polysomnographic recordings. Multiple sleep latency test was performed in 7 patients. RESULTS: Patients had 90% more arousals and awakenings (p<0.01) and the median length of occurrences of uninterrupted sleep in stages 2 and 3 and rapid eye movement (REM) sleep was 60% shorter than in controls (p<0.01). The overall amount of sleep stage shift from deeper to lighter sleep was 23.5+/-10.8 events in patients compared to 14.9+/-4.0 in controls (p<0.05). In 15 of 16 patients 15% of non-REM sleep consisted of alpha-delta (alpha-rating) sleep, compared with less than 1% in controls (p<0.001). Multiple sleep latency test for patients was 10.3+/-2.6 min. There were no differences between JRA and controls in self-reported questions. However, patients reported longer afternoon naps, 1.8+/-1.3 h compared to 0.3+/-0.8 h in controls (p<0.05). CONCLUSION: Objective polysomnographic evidence of abnormal sleep has been confirmed in patients with JRA. Sleep disturbance was associated with daytime sleepiness as evidenced by abnormal multiple sleep latency test and longer afternoon naptime.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

Thrombus formation of the right heart

We investigated the alteration of esophageal pressure (Pes) in 10 patients with upper-airway sleep-disordered breathing (UASDB) and the relationship among Pes, breathing patterns and EEG arousals. Increased negative Pes without apnea or hypopnea, appeared not only in upper airway resistance syndrome but also in obstructive sleep apnea syndrome. This phenomenon produced frequent EEG microarousals leading to sleep fragmentation and daytime sleepiness. Moreover, increased negative Pes occasionally continued for more than 20 min without an EEG arousal, which might be considered to be one of the factors to cause complications of UASDB.     

Overnight growth hormone secretion in achondroplasia: deconvolution analysis, correlation with sleep state, and changes after treatment of obstructive sleep apnea

The normal profile for overnight GH secretion in achondroplasia has not been previously studied. Factors that have been shown to influence GH secretion include age, obesity, sleep state, and the presence of obstructive sleep apnea (OSA). We assessed GH levels in a group of subjects with achondroplasia, during overnight polysomnography. Nineteen subjects with achondroplasia were studied at 11.3 y of age (median 6.7, range 1.8-30.9). Levels of GH were measured using time-resolved immunofluorometric assay (DELFIA, Pharmacia Biotech Inc.) and analyzed by a deconvolution method. Five subjects were restudied after treatment for OSA. Secretion rates of GH were greater in slow wave (SWS) and rapid eye movement (REM) sleep than in stage one and two (SI-II = light non-REM) sleep (p < 0.01). Total overnight GH secretion decreased with increasing age (r2 = 0.22 p < 0.04). Neither the frequency of arousals, frequency of sleep state transitions nor the severity of OSA correlated with measures of GH secretion. Levels of IGF-I correlated independently with age, body weight (percent ideal), and GH secretion rate (r2 = 0.76, p < 0.001). In a group of five subjects treated for OSA, improved respiratory distress index and reduced sleep state transitions were not associated with significant changes in GH secretion rate by sleep stage; SWS [from 0.62 +/- 0.28 mIU/L/min to 1.02 +/- 0.25 mIU/L/min (NS)] and SI-II sleep [from 0.26 +/- 0.07 mIU/L/min to 0.60 +/- 0.16 mIU/L/min (NS)]. However, in those five subjects, a GH secretion peak during the first 2 h of SWS was initially absent, appearing only after treatment of OSA (1.09 +/- 0.38 mIU/L/min) compared with (2.40 +/- 0.59 mIU/L/min (p = 0.01). A profile of overnight GH secretion is presented for subjects with achondroplasia.     

Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.     

Control of breathing in obstructive sleep apnoea and in patients with the overlap syndrome

In some patients obstructive sleep apnoea (OSA) may co-exist with chronic obstructive pulmonary disease (COPD) and respiratory failure; the so-called "overlap syndrome". Obstructive, hypercapnic patients have both blunted ventilatory and mouth occlusion pressure responses during CO2 stimulation. The purpose of this study was to compare the pattern of breathing and CO2 response between OSA patients and those with the overlap syndrome. Twenty obese men with OSA and normal lung function (Group A), 11 obese men with overlap syndrome (Group B) and 13 healthy nonobese subjects (Group C) were examined. Lung function tests, breathing pattern, mouth occlusion pressure (P0.2) at rest, and respiratory responses during CO2 rebreathing were investigated. Diagnosis of OSA was established by standard polysomnography. There were no statistical differences between Groups A and B in apnoea & hypopnoea index (62 vs 54), mean arterial oxygen saturation (SaO2) during sleep (85 vs 84%) and in body mass index (BMI) 34.3 vs 36.3 kg.m-2. Minute ventilation, mean inspiratory flow and P0.2 at rest were increased in both groups of patients in comparison to controls. During CO2 rebreathing, group A had normal ventilatory and P0.2 responses, similar to controls, (2.7 +/- 1.1 vs 2.1 +/- 0.4 l.min-1.mmHg-1 and 0.7 +/- 0.3 vs 0.71 +/- 0.25 cmH2O.mmHg-1, respectively). However, Group B had significantly decreased ventilatory and P0.2 responses to CO2 (0.71 +/- 0.23 l.min-1.mmHg-1 and 0.34 +/- 0.17 cmH2O.mmHg-1, respectively). This comparison showed that patients with OSA had normal CO2 response when awake, whereas those with overlap syndrome had diminished CO2 response when awake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrical stimulation of the lingual musculature in obstructive sleep apnea

The influence of lingual muscle activity on airflow dynamics in the upper airway was examined in nine patients with obstructive sleep apnea. Muscles that retract the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus) were selectively stimulated electrically during sleep with fine wire electrodes placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and 40-microseconds pulse duration did not elicit changes in electroencephalographic patterns or heart rate or alter airflow after the stimulation burst had ceased. The highest stimulus intensity that did not arouse patients from sleep was then utilized to examine the effect of lingual muscle recruitment on airflow dynamics during steady-state periods of inspiratory airflow limitation. When applying a stimulus burst during single inspirations, maximal inspiratory airflow decreased by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P < 0.001) compared with breaths immediately before and after the stimulated breath. When consecutive inspirations were stimulated repeatedly, protrusor stimulation decreased the frequency of obstructive breathing episodes in four patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest that stimulation of the lingual muscles can increase or decrease airflow depending on the specific muscles stimulated without arousing patients from sleep.     

Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea

OBJECTIVE: Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA. METHODS: The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23 69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing. RESULTS: Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34 (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo. CONCLUSION: Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.     

Environmental noise as a cause of sleep disruption in an intermediate respiratory care unit

Our laboratory previously reported continuously monitored peak sound levels in several areas at Rhode Island Hospital. The number of sound peaks greater than 80 A-weighted decibels (dBA) was found to be high in the intensive and intermediate respiratory care unit (IRCU) areas, even at night. Environmental noise of this magnitude is potentially sleep-disruptive. Therefore, we hypothesized that nocturnal peak sound levels of > or = 80 dBA would be associated with an increase in EEG arousals from sleep in patients in the IRCU. Six patients underwent sleep monitoring while environmental peak sound levels were continuously recorded. Each 8-hour period (2200 to 0600 hours) was broken down into 30-minute segments. If there were 10 minutes or more of wakefulness in a segment, that segment was dropped from further analysis. Of the remaining 61 segments, there was a very strong correlation (r = 0.57, p = 0.0001) between the number of sound peaks of > or = 80 dBA and arousals from sleep. These 61 periods were then classified as quiet, moderately loud, and very loud based on the number of sound peaks (< or = 5, 6-15, and > 15, respectively). Analysis of variance revealed a significant difference between the number of arousals (p = 0.001) in quiet periods and that in very loud periods. We conclude that environmental noise may be an important cause of sleep disruption in the IRCU.     

Simultaneous laboratory-based comparison of ResMed Autoset with polysomnography in the diagnosis of sleep apnoea/hypopnoea syndrome

ResMed Autoset (AS) is a simplified diagnosis system for obstructive sleep apnoea/hypopnoea syndrome (OSAS) based on the respiratory flow/time relationship by pressure variation measured through simple nasal prongs. A multicentre prospective trial was used to compare AS and polysomnography (PSG) for diagnosing 95 patients, with suspected OSAS. Physicians gave a pretest probability of the patient having OSAS. The apnoea/hypopnoea index (AHI) was compared between the two methods of diagnosis for the whole population and for subgroups according to the pretest probability. Twenty-four patients had AHI < 15 events x h(-1) on PSG and 19 AHI 15-30, and 52 patients had AHI > or = 30. Correlation between AHI assessed by AS and PSG was r=0.87 for total sleep time (TST), p<0.0001. A Bland and Altman plot gave an agreement between the two methods of +/-40%. For a threshold of AHI > or = 15 events x h(-1) to diagnose OSAS, AS has a sensitivity of 92%, specificity of 79%, positive predictive value of 93% and negative predictive value of 76%. With a pretest probability > or = 80%, sensitivity and positive predictive value were 98 and 100% respectively. Of six false negative, four had a high pretest probability (> 80%) or Epworth score > or = 10. Using these parameters as a criterion for proceeding to PSG after a negative AS study would mean that two apnoeic patients (AHI 20 and 17 events x h(-1) by PSG) would escape detection. The Autoset is useful for the detection of obstructive sleep apnoea but with high pretest probability and a negative Autoset result polysomnography should be performed.     

Residual effect of nCPAP applied for part of the night in patients with obstructive sleep apnoea

The aim of the present study was to assess whether nasal continuous positive airway pressure (nCPAP) treatment, applied for only a few hours at the beginning of the night, has any residual effect on sleep and breathing during the ensuing hours of unassisted sleep in patients with obstructive sleep apnoea syndrome (OSAS). In 27 patients with newly-diagnosed OSAS, effective nCPAP was applied during the first part of the night and then withdrawn. Polysomnographic parameters after nCPAP withdrawal were compared with those of the corresponding part of the diagnostic polysomnography performed a few days or weeks before and with those of the first part of night on nCPAP. After 255+/-63 (mean+/-SD) min of sleep with normalization of sleep and breathing parameters under nCPAP, there was partial improvement of OSAS severity during the remaining 124+/-56 min of nocturnal sleep without treatment; mean oxygen saturation, desaturation index (equivalent to the apnoea/hypopnoea index) and movement arousal index all improved significantly with respect to the diagnostic night (p=0.001). This improvement was not accounted for by a change in sleep architecture. We conclude that there is an improvement in severity of obstructive sleep apnoea syndrome after only 4 h of nasal continuous positive airway pressure. This carryover effect could explain why a number of patients with obstructive sleep apnoea syndrome apply nasal continuous positive airway pressure for only part of the night or not every night.     

Relationship between sleep patterns and human colonic motor patterns

BACKGROUND/AIMS: The precise relationships among colonic motor patterns, depth of sleep, and awakening are incompletely understood. The aim of this study was to correlate human colonic motor patterns with sleep stage, nocturnal arousals, and waking. METHODS: We monitored sleep and correlated sleep stage, arousals, and waking with pressures (area under curve and propagating contractions) recorded from the entire colon in 11 healthy volunteers. RESULTS: Propagating contraction frequency (P = 0.01) and area under the curve (P = 0.001) were significantly reduced at night. There was a highly significant correlation between depth of sleep and suppression of area under curve (P = 0.001) and propagating contraction frequency (P = 0.0001). Propagating contractions were eliminated during slow-wave sleep. During rapid eye movement sleep, colonic pressure and propagating contraction frequency increased sharply to levels comparable with those found in stage 2 sleep. Transient arousal from stable sleep, with or without waking, was a potent and immediate stimulus for colonic propagating contractions. CONCLUSIONS: Sleep per se has a profound inhibitory effect on propagating and nonpropagating activity and is the major determinant of diurnal variation of colonic motility. Propagating contractions are eliminated in slow-wave sleep. Rapid eye movement sleep, arousals, and waking have immediate stimulatory effects on colonic motility.     

Hormonal secretion during nighttime sleep indicating stress of daytime exercise

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800-2030), and 3) LDE of moderate intensity (biking 120-150 km; 1600-2030). During the subsequent night (2300-0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.     

Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea

BACKGROUND: Muscle sympathetic nerve activity (MSNA) is increased in patients with obstructive sleep apnea (OSA). We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in OSA. METHODS AND RESULTS: Using a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation (by comparing effects of breathing 100% oxygen for 15 minutes with effects of breathing room air for 15 minutes) on MSNA, heart rate, blood pressure, and minute ventilation in 14 untreated patients with OSA and in 12 normal subjects matched for age and body mass index. All control subjects underwent overnight polysomnography to exclude the existence of occult OSA. Baseline MSNA was markedly elevated in the patients with OSA compared with the control subjects (44+/-4 versus 30+/-3 bursts per minute; P=.01). In both control subjects and patients with OSA, heart rate decreased during administration of 100% oxygen but did not change during administration of room air. By contrast, both MSNA (P=.008) and mean arterial pressure (P=.02) were significantly reduced during chemoreflex deactivation by 100% oxygen only in patients with OSA but not in control subjects. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents may contribute to increased efferent sympathetic activity to muscle circulation in patients with OSA.     

Respiratory arousal from sleep: mechanisms and significance

The mechanisms by which respiratory stimuli induce arousal from sleep and the clinical significance of these arousals have been explored by numerous studies in the last two decades. Evidence to date suggests that the arousal stimulus in nonrapid eye movement sleep (NREM) is related to the level of inspiratory effort rather than the individual stimuli that contribute to ventilatory drive. A component of the arousal stimulus proportional to the level of inspiratory effort may originate in mechanoreceptors either in the upper airway or respiratory pump. Medullary centers responsible for ventilatory drive may also send a signal proportionate to the level of drive to higher centers in the brain which are responsible for arousal. Thus, the arousal stimulus may consist of multiple components, each increasing as inspiratory effort increases. The level of effort triggering arousal is an index of the arousability of the brain (arousal threshold). A deeper stage of sleep, central nervous system depressants, prior sleep fragmentation, and the presence of obstructive sleep apnea (OSA) have been observed to increase the arousal threshold to airway occlusion. Less information is available concerning the mechanisms of arousal from rapid eye movement (REM) sleep. While REM sleep is associated with the longest obstructive apneas in patients with OSA, normal human subjects appear to have a similar or lower arousal threshold to respiratory stimuli in REM compared to NREM sleep. Recent studies have challenged the assumption that the termination of all obstructive apnea is dependent on arousal from sleep. Improvements in methods to detect and quantitate changes in the cortical electroencephalogram (EEG) may better define the relationship between arousal and apnea termination. This may result in improved criteria for identifying EEG changes of clinical significance. While little is known concerning the mechanisms of arousal in central sleep apnea, arousal may play an important role in inducing this type of apnea in some patients.     

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

We hypothesized that reductions in arterial PCO2 (PaCO2) below the apnea threshold play a key role in the pathogenesis of idiopathic central sleep apnea syndrome (ICSAS). If so, we reasoned that raising PaCO2 would abolish apneas in these patients. Accordingly, patients with ICSAS were studied overnight on four occasions during which the fraction of end-tidal CO2 and transcutaneous PCO2 were measured: during room air breathing (N1), alternating room air and CO2 breathing (N2), CO2 breathing all night (N3), and addition of dead space via a face mask all night (N4). Central apneas were invariably preceded by reductions in fraction of end-tidal CO2. Both administration of a CO2-enriched gas mixture and addition of dead space induced 1- to 3-Torr increases in transcutaneous PCO2, which virtually eliminated apneas and hypopneas; they decreased from 43.7 +/- 7.3 apneas and hypopneas/h on N1 to 5.8 +/- 0.9 apneas and hypopneas/h during N3 (P < 0.005), from 43.8 +/- 6.9 apneas and hypopneas/h during room air breathing to 5.9 +/- 2.5 apneas and hypopneas/h of sleep during CO2 inhalation during N2 (P < 0.01), and to 11.6% of the room air level while the patients were breathing through added dead space during N4 (P < 0.005). Because raising PaCO2 through two different means virtually eliminated central sleep apneas, we conclude that central apneas during sleep in ICSA are due to reductions in PaCO2 below the apnea threshold.     

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

BACKGROUND: Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4 degrees C. METHODS: Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42 degrees C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured. RESULTS: Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63+/-4 mm Hg versus 44+/-4 mm Hg, p<0.05) heart rate x developed pressure (13,883+/-1,174 beats per minute x mm Hg versus 8,492+/-1,564 beats per minute x mm Hg, p<0.05), rate of ventricular pressure increase (1,912+/-112 mm Hg/second versus 1,215+/-162 mm Hg/second, p<0.005), rate of ventricular pressure decrease (1,258+/-89 mm Hg/second versus 774+/-106 mm Hg/second, p<0.005). Diastolic compliance and lactate dehydrogenase release were improved in heatshocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (>threefold) compared with sham-treated animals and controls. CONCLUSIONS: Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.