Polysomnographic characteristics of severe obstructive sleep apnea vary significantly between hypertensive and normotensive patients of both genders.

PURPOSE: Hypertension is a common finding in patients with obstructive sleep apnea (OSA), but it has remained unclear whether or not the amount of disturbed breathing and characteristics of individual respiratory events differ between hypertensive and normotensive patients with severe OSA. METHODS: Full polysomnographic recordings of 323 men and 89 women with severe OSA were analyzed. Differences in the duration of individual respiratory events, total apnea and hypopnea times, and the percentage of disturbed breathing from total sleep time (AHT%) were compared between normotensive and hypertensive patients separately by genders. Furthermore, differences in the respiratory event characteristics were assessed between three AHT% groups (AHT% ≤ 30%, 30% < AHT% ≤ 45%, and AHT% > 45%). RESULTS: Hypertensive women had lower percentage apnea time (15.2% vs. 18.2%, p = 0.003) and AHT% (33.5% vs. 36.5%, p = 0.021) when compared with normotensive women. However, these differences were not observed between hypertensive and normotensive men. Percentage hypopnea time was higher in hypertensive men (13.5% vs. 11.2%, p = 0.043) but not in women (15.2% vs. 12.2%, p = 0.130) compared with their normotensive counterparts. The variation in AHI explained 60.5% (ρ = 0.778) and 65.0% (ρ = 0.806) of the variation in AHT% in normotensive and hypertensive patients, respectively. However, when AHT% increased, the capability of AHI to explain the variation in AHT% declined. CONCLUSIONS: There is a major inter- and intra-gender variation in percentage apnea and hypopnea times between hypertensive and normotensive patients with severe OSA. OSA is an important risk factor for hypertension and thus, early detection and phenotyping of OSA would allow timely treatment of patients with the highest risk of hypertension.

Standardized framework to report on the role of sleeping position in sleep apnea patients.

PURPOSE: Sleep apnea is a multifactorial illness which can be differentiated in various physiological phenotypes as a result of both anatomical and non-anatomical contributors (e.g., low respiratory arousal threshold, high loop gain). In addition, the frequency and duration of apneas, in the majority of patients with OSA, are influenced by sleeping position. Differences in characteristics between non-positional patients (NPP) and positional patients (PP) suggest another crucial phenotype distinction, a clinical phenotype focusing on the role of sleeping position on sleep apnea. Since this clinical phenotype distinction has therapeutic implications, further research is necessary to better understand the pathophysiology behind this phenotypic trait and to improve management of PP. Therefore, we suggest a standardized framework that emphasizes the role of sleeping position when reporting clinical and research data on sleep apnea. METHODS: We identified 5 key topics whereby a standardized framework to report on the role of sleeping position would be of added value: (1) sleep study data, (2) anatomical, morphological and physiological factors, (3) drug-induced sleep endoscopy (DISE) findings, (4) sleep apnea management, and (5) effectiveness versus efficacy of positional therapy in sleep apnea management. We performed a literature search to identify evidence to describe and support the rationale behind these 5 main recommendations. RESULTS: In this paper, we present the rationale behind this construct and present specific recommendations such as reporting sleep study indices (disease severity) and sleep time spent in various sleeping positions. The same is suggested for DISE findings and effect of treatment. Sleep study indices (disease severity), anatomical, morphological, and physiological factors in sleep apnea patients should be reported separately for PP and NPP. CONCLUSION: Applying these suggestions in future research will improve patient care, assist in better understanding of this dominant phenotype, and will enhance accurate comparisons across studies and future investigations.

Total durations of respiratory events are modulated within REM and NREM sleep by sleeping position and obesity in OSA patients.

BACKGROUND: Supine sleeping position and obesity are well-known risk factors for obstructive sleep apnea (OSA) and modulate the risk for OSA-related daytime symptoms. Although respiratory event durations are associated with OSA-related severe health consequences, it is unclear how sleeping position, obesity, and daytime sleepiness are associated with respiratory event durations during REM and NREM sleep. We hypothesize that irrespective of the apnea-hypopnea index (AHI), respiratory event durations differ significantly between various OSA subgroups during REM and NREM sleep. METHODS: One night in-lab polysomnographic recordings were retrospectively analyzed from 1910 untreated suspected OSA patients. 599 patients (AHI ≥ 5) were included in study and divided into subgroups based on positional dependency, BMI, and daytime sleepiness (Epworth Sleepiness Scale and Multiple Sleep Latency Test). Differences in total hypopnea time (THT), total apnea time (TAT), and total apnea-hypopnea time (TAHT) within REM and NREM sleep between the subgroups were evaluated. RESULTS: During REM sleep, positional OSA patients had lower THT (OR = 0.952, p < 0.001) and TAHT (OR = 0.943, p < 0.001) than their non-positional counterparts. Compared to normal-weight patients (BMI < 25 kg/m2), obese patients (BMI ≥ 30 kg/m2) had lower THT, TAT, and TAHT (ORs = 0.942-0.971, p ≤ 0.009) during NREM sleep but higher THT (OR = 1.057, p = 0.001) and TAHT (OR = 1.052, p = 0.001) during REM sleep. No significant differences were observed in THT, TAT, and TAHT between patients with and without daytime sleepiness. CONCLUSION: Regardless of the AHI, respiratory event durations vary significantly between OSA sub-groups during REM and NREM sleep. Therefore, to personalize OSA severity estimation the diagnosis should be tailored based on patient's demographics, clinical phenotype, and PSG characteristics.

Progression of snoring and obstructive sleep apnoea: the role of increasing weight and time.

The aim of the present study was to examine the natural evolution of primary snoring and obstructive sleep apnoea (OSA) in adult male patients. Retrospective analysis was performed on 160 untreated patients with primary snoring and mild, moderate and severe OSA who had two polysomnographic recordings. The mean time between recordings (TBR) was 5.1+/-3 yrs. The mean apnoea/hypopnoea index (AHI), body mass index (BMI), and lowest arterial oxygen saturation level during rapid eye movement (REM) and non-REM sleep showed a significant worsening effect. The change in AHI differed among the groups showing a similar significant increase in AHI for primary snoring, mild and moderate OSA and an insignificant decrease for severe OSA patients. Stepwise linear regression showed that only DeltaBMI and time were significant predictors for AHI change. A model for the mean AHI change showed that DeltaAHI = (4.33xDeltaBMI) + (0.66xTBR). After adjusting for confounders, multiple regression analysis indicated that age and high BMI, but not AHI, were significant risk factors for developing hypertension and/or cardiovascular disease. Patients with primary snoring and mild and moderate obstructive sleep apnoea had a similar increase in the apnoea/hypopnoea index over time, which depended mainly on weight gain and, to a lesser extent, on time.

Elevated healthcare utilisation in young adult males with obstructive sleep apnoea.

The aim of the present study was to explore morbidity and healthcare utilisation among young adult males with obstructive sleep apnoea (OSA) compared with middle-aged OSA patients over the 5-yr period preceding diagnosis. A prospective case-control study was performed; 117 young (22-39-yr-old) males with OSA were matched with 117 middle-aged (40-64-yr-old) OSA males for body mass index, apnoea/hypopnoea index, arterial oxygen saturation, arousal and awakening index, and Epworth Sleepiness Scale score. Each OSA patient was matched with controls by age, geographic area and physician. Young adult males with OSA showed no increase in specific comorbidity compared with controls. Middle-aged OSA patients exhibited increased risk of cardiovascular disease. Healthcare utilisation for the 5-yr period was >or=1.9 times higher among young and middle-aged male OSA patients than among controls. Multiple logistic regression analysis revealed that hyperlipidaemia in young adults and a body mass index of >37 kg x m(-2) and cardiovascular disease in middle-aged adults are the only independent determinants of the upper third, most costly, OSA patients. Compared with middle-aged males with obstructive sleep apnoea, in whom increased expenditure was related to cardiovascular disease and body mass index, utilisation was not related to any specific disease in younger cases.

Essential hypertension and abnormal upper airway resistance during sleep.

The epidemiological, clinical, hereditary, biochemical, hematological, and physiological characteristics of essential hypertension (EH) and obstructive sleep apnea (OSA) are reviewed here. This extensive review shows that essential hypertension and sleep-disordered breathing--independently of whether it is OSA syndrome or upper airway resistance syndrome--share strikingly similar characteristics. The accumulated data obtained by many different researchers support the hypothesis that EH is mainly due to increased upper airway resistance during sleep. If this hypothesis is correct, treating disorders that cause increased upper airway resistance, particularly during sleep, would be an important part of the treatment of essential hypertension.

Phasic activities of rapid eye movement sleep in vegetative state patients.

STUDY OBJECTIVES: To assess the phasic components of rapid eye movement (REM) sleep in patients in vegetative state and to evaluate the possible relationship of these activities to patient outcome. SETTING: Sleep disorders unit at a major rehabilitation hospital. DESIGN: Comparative control study. PATIENTS: Eleven patients in vegetative state (10 males and 1 female) aged 17-53 years. INTERVENTIONS: Continuous 24-hour polysomnographic recording. MEASUREMENTS AND RESULTS: All the patients had REM sleep periods during the 24-hr recording session. Mean total REM sleep time for the whole session was 66.5 +/- 34.9 min, and for the nocturnal hours only, 37.3 +/- 19.7 min. Comparison with the control group (79.2 +/- 11.5 min) yielded a significant difference only for nocturnal REM sleep time (p<0.0003). The duration of the REM sleep periods was significantly shorter in the patients than the controls for the whole 24-hr session (10.9 +/- 6.0 vs.19.6 +/- 4.9 min, p<0.008), but not for the nocturnal period alone. Compared to controls, the density of rapid eye movements (REMs) (p=0.001), chin twitches (p=0.002), and leg muscle twitches (p=0.023) was significantly lower in the patient group. The density of the sawtooth waves was also lower in the patients, but the difference did not reach significance (p=0.069). Similar results were obtained when the comparison was done only for the nocturnal period. There was no significant difference for any of the REM sleep characteristics or REM sleep phasic activities (24-hr, nocturnal and diurnal periods) between the patients who recovered consciousness and those who did not. CONCLUSIONS: The present study shows that patients in vegetative state have a significant reduction in the phasic activities of REM sleep. However, the amount of these activities is unrelated to recovery from the clinical condition. These findings may reflect possible damage to the pedunculopontine tegmentum cholinergic mechanisms in vegetative state.

Sleep-related erections in vegetative state patients.

STUDY OBJECTIVES: To determine whether sleep-related erections occur in vegetative state and if so, to investigate their relationship with rapid eye movement (REM) sleep. DESIGN: N/A. SETTING: Major rehabilitation hospital. PATIENTS: Nine male patients in vegetative state aged 17-40 years. INTERVENTIONS: Continuous 24-hour polysomnographic recordings including penile circumferencial changes. MEASUREMENTS AND RESULTS: Sleep-related erection episodes (SREe's) were noted in all nine patients, ranging in number from 1-7/24 hr (average 4.4+2.4) and lasting 6 to 50 min (average 22.0+5.7 min). The number of REM periods (REMp's) ranged from 4-11 (average 6.6+2.5) and lasted for 1.0 to 44.0 min (average 16.0+6.6 min). Ninety-five percent of the SREe's recorded were associated with REMp's, usually (76.3%) appearing simultaneously with the REMp or soon thereafter; 64.6% of the REMp's were associated with SRE's. For both the nocturnal and diurnal periods, there were more REMp's with SREe's than without, and the REMp's associated with SREe's were of longer duration (by 25.5% and 28.4%, respectively). There were no statistically significant differences for any of the REMp or SREe parameters between the recovered and nonrecovered patients. CONCLUSIONS: The sleep-related erection characteristics of patients in vegetative state are similar to those of normal individuals. These findings may have implications for the assessment of the reorganization of REM sleep during recovery from vegetative state and may further help in our understanding of the pathophysiology of vegetative state. More studies are needed in larger groups of patients.

REM sleep deprivation in monocularly occluded kittens reduces the size of cells in LGN monocular segment.

STUDY OBJECTIVES: In this study, we test the hypothesis that when REM-state activation (which impinges upon all lateral geniculate nucleus laminae irrespective of stimulating eye) is deprived, the monocular segment (MS) that is cut off from visual input and also deprived of REM-state activation will exhibit smaller cells, owing to the loss of extrinsic as well as intrinsic activation. DESIGN: We carried out a study comparing soma sizes in the MSs of kittens subjected to monocular deprivation (MD) + REM deprivation (RD) to two age-matched nonRD groups, MD ONLYs and MD MOMS (MD kittens living in their home cages). MEASUREMENTS AND RESULTS: Perikaryal outlines of 100 cells in each of the bilateral MSs were measured. As predicted, mean cell size in the MS connected to the patched eye of MD + RD kittens, but in neither of the control groups, was significantly smaller than in the MS afferented by the nonpatched eye. One-way ANOVAs comparing MS cell-size means from the same sides across groups were also significant, but the two MSs showed different results on post hoc tests. The ordering of MS cell-size means correlated significantly with a measure that aggregates the sources of activation reaching a particular MS and their durations. CONCLUSIONS: These results reveal that removal of REM-state activation during CNS development amplifies the plasticity processes generated when normal visual afferentation to central visual areas is interrupted. Our findings in the MS of the LGN indicate that during the usual operation of REM sleep, central visual-sensory sites receive intrinsic activation that, in the visual system, is additive and complementary to the stimulation obtained from extrinsic sources. In the course of early development, normative symmetrical activation of central visual areas during REM sleep may counterbalance plasticity changes caused either by absent or aberrant sensory stimulation.

The effect of body posture on sleep-related breathing disorders: facts and therapeutic implications.

The aggravating effect of the supine body position on breathing abnormalities during sleep was recognized from the earliest studies on sleep breathing disorders. Most of the anatomical and physiological correlates of this phenomenon appear to be due to the effect of gravity on the upper airway. Although few articles have been published on this topic, it has been shown in a large population of obstructive sleep apnoea (OSA) patients that more than half of them are Positional Patients, i.e. they have at least twice as many apnoeas/hypopnoeas during sleep in the supine posture as in the lateral position. This positional phenomenon is influenced by factors such as Respiratory Disturbances Index (RDI), Body Mass Index (BMI), age and sleep stages. The sleep supine posture not only increases the frequency of the abnormal breathing events but also their severity. This sleep posture also has a detrimental effect on snoring, as well as on the optimal CPAP pressure. Positional Therapy, i.e. the avoidance of the supine posture during sleep, is a simple behavioural therapy for many mild to moderate OSA patients. Unfortunately, only a few studies, including only a few patients, have investigated this form of therapy. Although the results of these studies are promising, the lack of a reliable long-term evaluation of its efficacy is perhaps an important reason why this form of therapy has not been widely accepted. Since mild to moderate OSA patients are the majority of the OSA patients and since without treatment, a large percentage of them will develop a more severe form of the disease, a thorough evaluation with a major emphasis on the long-term effectiveness of this form of therapy is urgently needed.

Association of body position with severity of apneic events in patients with severe nonpositional obstructive sleep apnea.

STUDY OBJECTIVE: To compare the severity of sleep apneic events occurring in the supine posture vs the severity of sleep apneic events occurring in the lateral posture in patients with severe obstructive sleep apnea (OSA). DESIGN: A retrospective analysis of apneic event variables in a group of 30 OSA patients who underwent a complete polysomnographic evaluation in our sleep disorders unit. PATIENTS: Thirty patients with severe OSA (respiratory disturbance index [RDI] = 70.1+/-18.2) who were nonpositional patients (NPP), ie, in whom the ratio of the supine RDI to the lateral RDI is < 2 (supine RDI = 85.7+/-11.7, lateral RDI = 64.8+/-17.3), and who had > or =30 apneic events in the lateral position and 30 apneic events in the supine position during sleep stage 2 were included in the study. MEASUREMENTS: For the 30 apneic events in each body position, the following variables were evaluated: apnea duration (ApDur), minimum desaturation (MinDes), Delta desaturation (Delta-Des), duration of arousal (DurArous), maximum snoring loudness (MaxSL), and Delta heart rate (Delta-HR). In addition, three other variables assessed as a ratio of ApDur (Rate-D = Delta-Des/ApDur, R-HR =Delta-HR/ApDur, and R-Arous = DurArous/ApDur) were also calculated. RESULTS: For all variables evaluated, apneic events occurring in the supine posture were significantly more severe than those apneic events occurring in the lateral posture during sleep stage 2. ApDur of both body postures correlated significantly with DurArous, Delta-HR, and MaxSL, but not with Delta-Des and MinDes. ApDur correlated linearly with DurArous for both postures. The slopes of the two regression lines were similar (p = 0.578) but the regression line intercept for the supine apneas was significantly higher than that of lateral apneas (p<0.0001). In addition, the average number of supine apneic events that did not end with an arousal was smaller than the average number of lateral apneic events not ending with an arousal (4.4+/-6.0 vs. 10.5+/-6.7, respectively; p< 0.0001). Also, only 4 of 900 (0.44%) apneic events analyzed in the lateral posture ended with an awakening (> 15 s), whereas in the supine posture, there were 37 (4.1%) such events (p<0.001). CONCLUSIONS: These results show that even in patients with severe OSA who have a high number of apneic events in the supine and lateral posture, the apneic events occurring in the supine position are more severe than those occurring while sleeping in the lateral position. Thus, it is not only the number of apneic events that worsen in the supine sleep position but, probably no less important, the nature of the apneic events themselves.

Positional vs nonpositional obstructive sleep apnea patients: anthropomorphic, nocturnal polysomnographic, and multiple sleep latency test data.

STUDY OBJECTIVES: To compare anthropomorphic, nocturnal polysomnographic (PSG), and multiple sleep latency test (MSLT) data between positional (PP) and nonpositional (NPP) obstructive sleep apnea (OSA) patients. DESIGN: This is a retrospective analysis of anthropomorphic, PSG, and MSLT data of a large group of OSA patients who underwent a complete PSG evaluation in our sleep disorders unit. The patients were divided in two groups: the PP group, those patients who had a supine respiratory disturbance index (RDI) that was at least two times higher than the lateral RDI, and the NPP group, those patients in whom the RDI in the supine position was less than twice that in the lateral position. SUBJECTS: From a group of 666 consecutive OSA patients whose conditions were diagnosed in our unit from September 1990 to February 1995, 574 patients met the following criteria and were included in the study: RDI > 10; age > 20 years, and body mass index (BMI) > 20. RESULTS: Of all 574 patients, 55.9% were found to be positional. No differences in height were observed but weight and BMI were significantly higher in the NPP group, these patients being on the average 6.5 kg heavier than those in the PP group. The PP group was, on average, 2 years younger than the NPP group. Nocturnal sleep quality was better preserved in the PP group. In this group, sleep efficiency and the percentages of deep sleep (stages 3 and 4) were significantly higher while the percentages of light sleep (stages 1 and 2) were significantly lower than in the NPP group. No differences for rapid eye movement (REM) sleep were found. In addition, wakefulness after sleep onset and the number of short arousals (< 15 s) were significantly lower in the PP group. Apnea index and total RDI were significantly higher and the minimal arterial oxygen saturation in REM and non-REM sleep was significantly lower in the NPP. No differences in periodic limb movements data were found between the two groups. The average MSLT was significantly shorter in the NPP group. Univariate and multivariate stepwise logistic regression analysis showed that the most dominant variable that correlates with positional dependency in OSA patients is RDI, followed by BMI which also adds a significant contribution to the prediction of positional dependency. Age, although significant, adds only a minor improvement to the prediction of this positional dependency phenomenon. A severe, obese, and older OSA patient is significantly less likely to be positional than a mild-moderate, thin, and young OSA patient. In four obese OSA patients who lost weight, a much more pronounced reduction was seen in the lateral RDI than in the supine RDI, and three of these cases who were previously NPP became PP. CONCLUSIONS: In a large population of OSA patients, most were found to have at least twice as many apneas/hypopneas in the supine than in the lateral position. These so-called "positional patients" are on the average thinner and younger than "nonpositional patients." They had fewer and less severe breathing abnormalities than the NPP group. Consequently their nocturnal sleep quality was better preserved and, according to MSLT data, they were less sleepy during daytime hours. RDI was the most dominant factor that could predict the positional dependency followed by BMI and age. RDI showed a threshold effect, the prevalence of PP in those with severe RDI (RDI > or = 40) was significantly lower than in those OSA patients with mild-moderate RDI. BMI showed a major significant inverse relationship with positional dependency, while age had only a minor although significant inverse relationship with it. Body position during sleep has a profound effect on the frequency and severity of breathing abnormalities in OSA patients.

The sleep supine position has a major effect on optimal nasal continuous positive airway pressure : relationship with rapid eye movements and non-rapid eye movements sleep, body mass index, respiratory disturbance index, and age.

STUDY OBJECTIVES: To evaluate the impact of sleep position on optimal nasal continuous positive airway pressure (nCPAP [op-nCPAP]) in obstructive sleep apnea (OSA) patients and to investigate how rapid eye movements (REM) and Non-REM (NREM) sleep, body mass index (BMI), respiratory disturbance index (RDI), and age are related to this effect. DESIGN: Retrospective analysis. SETTING: Sleep Disorders Unit at Loewenstein Hospital Rehabilitation Center. PATIENTS: Eighty-three consecutive adult OSA patients who underwent a complete nCPAP titration. From this group, 60 patients who spent at least 30 min in both the supine (Sup) and lateral (Lat) positions and 46 patients who had data on both positions during REM and NREM sleep were included in the analysis. RESULTS: In most OSA patients (52; 86.7%), the recommended op-nCPAP was obtained when the patients slept in the Sup posture. The mean op-nCPAP was significantly higher in the Sup posture (10.00 +/- 2.20 cm H(2)O) than it was in the Lat posture (7.61 +/- 2.69 cm H(2)O). The op-nCPAP was significantly higher in the Sup position than it was in the Lat position in both REM and NREM sleep, as well as in the severe BMI group (BMI >/= 30) and in the less obese group (BMI < 30). Similarly, in the severe (RDI >/= 40) and less severe groups (RDI < 40), as well as in both age groups (< and > 60 years of age), the op-nCPAP was significantly higher in the Sup posture than it was in the Lat posture. Irrespective of the four parameters mentioned, the actual differences in op-nCPAP between the two body postures were almost identical, ranging between 2.31 and 2.66 cm H(2)O. CONCLUSIONS: For most OSA patients, the op-nCPAP level is significantly higher in the Sup position than it is in the Lat position. This is true for REM and NREM sleep, for obese and nonobese patients, for patients with different degrees of severity, and for young and old OSA patients. Since the op-nCPAP was highest in the Sup posture during REM sleep, no nCPAP titration should be considered complete without the patient having slept in the Sup posture during REM sleep.

Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated.

There is now strong evidence from animal studies and, in humans, from epidemiological studies as well as from retrospective and prospective intervention studies, that obstructive sleep apnea (OSA) can cause persistent hypertension not only during sleep but during waking hours as well. There is also some evidence that habitual snoring alone, even without OSA, can do the same. Many of the hitherto unexplained epidemiological, clinical, biochemical, hematological, and physiological abnormalities seen in essential hypertension (EH) could be explained by the accompanying sleep related breathing disorders (SRBD). Many cases of resistant hypertension are probably due to SRBD. Recent studies show that SRBD are extremely common in EH but that the vast majority of patients with these sleep disorders are being missed by physicians who are treating the accompanying hypertension, even when the patients already have blatant symptoms of OSA. Recent investigations have shown that the probable reason for this underdiagnosis of OSA is lack of physician knowledge about the condition. This lack of knowledge is prevalent not only among family physicians, but among hypertension specialists and researchers in the field of hypertension as well. OSA is a common, easily diagnosed, and eminently treatable condition that is associated not only with disturbed sleep, loud snoring and excessive daytime sleepiness (which greatly increases the risk of traffic accidents), but also with hypertension, especially resistant hypertension, a broad range of cardiovascular problems, decreased sexual functioning, memory deficits, difficulty concentrating, and changes in personality and mood. It deserves much more attention by physicians treating hypertension than it is currently getting.

Dissociation between sleep-related and TRH-induced prolactin secretion in seminiferous tubule failure.

Prolactin (PRL) secretion has been measured during sleep and following TRH administration in 8 patients aged 24-39 yr with seminiferous tubule failure and 36 controls. Basal LH levels were 25.7 +/- 14.7 mIU/ml in the patients compared to 11.5 +/- 4.2 mIU/ml in the controls (p less than 0.01) Corresponding FSH levels were 26.2 +/- 10.7 mIU/ml and 5.9 +/- 2.1 mIU/ml (p less than 0.001) Mean estradiol 17B and testosterone levels were similar in the 2 groups. The mean PRL secretion during sleep was 16.5 +/- 11.7 ng/ml in the patients and not different in 11 of the controls (12.4 +/- 3.2 ng/ml). One patient had a mean nocturnal PRL concentration of 44.1 ng/ml. In both groups, the mean sleep related PRL concentration was greater than that during waking hours. The average number of peaks in the 2 groups was similar. In the same patients, the peak PRL response to TRH (200 ug IV) was 81.9 +/- 18.8 ng/ml as compared to 32.1 +/- 10.7 ng/ml in the controls (p less than 0.001). It is concluded that PRL concentrations following pharmacological stimulation are increased in seminiferous tubule failure, whereas levels are normal in relation to the physiological stimulus of sleep.

Is vasoactive intestinal polypeptide (VIP) a sleep factor?

Vasoactive intestinal peptide (VIP) was tested in order to determine its hypnogenic properties in cats. VIP was administered intraventricularly in doses of 10 and 100 ng and compared to Ringer controls. In addition the dose of 100 ng was tested in cats pretreated with 150 mg/kg of chloramphenicol (CAP). The results showed that the 100 ng dose of VIP had small but significant REM enhancing properties, but that it did not protect the animals from the specific REM inhibiting properties of CAP. The results suggest that VIP may participate in the regulation of REM sleep.

A functional role for REM sleep in brain maturation.

The biological function of REM sleep is defined in terms of the functions of neural processes that selectively operate during the REM sleep state. The high amounts of REM sleep expressed by the young during a period of central nervous system plasticity suggest that one function of REM sleep is in development. The phenomenon of activity-dependent development has been clearly shown to be one mechanism by which early sensory experience can affect the course of neural development. Activity-dependent development may be a ubiquitous process in brain maturation by which activity in one brain region can influence the developmental course of other regions. We hypothesize an ontogenetic function of REM sleep; namely, the widespread control of neuronal activity exerted by specific REM sleep processes help to direct brain maturation through activity-dependent developmental mechanisms. Preliminary tests of the hypothesis have been conducted in the developing feline visual system, which has long been known to incorporate information derived from visual experience in establishing neuronal connectivity. We find that suppression of REM sleep processes by an instrumental REM deprivation procedure results in a significant enhancement of the effects of altered visual experience by monocular occlusion. Bilateral brainstem lesions that selectively block the occurrence of ponto-geniculo-occipital (PGO) waves are sufficient to produce similar results. These data indicate that the propagation of phasic influences during REM sleep interacts with other processes subserving neural development. This source of influence appears not to derive from the environment but rather stems from an intrinsic source of genetic origin. Examination of the neural activity associated with PGO waves in the lateral geniculate nucleus reveals a distribution of facilitatory influence markedly different from that induced by visual experience. We conclude that REM sleep directs the course of brain maturation in early life through the control of neural activity.

Rapid eye movement sleep deprivation in kittens amplifies LGN cell-size disparity induced by monocular deprivation.

The abundance of rapid eye movement (REM) sleep in the neonatal mammal and its subsequent decline in the course of development, as well as the dramatic and widespread enhancement of CNS activity during REM sleep, led us to propose that this state plays a functional role in the normative physiological and structural maturation of the brain [54]. When, after 1 week of monocular deprivation (MD), a second week of MD was coupled with behavioral deprivation of REM sleep, the structural alteration in the visual system provoked by MD alone (interlaminar relay cell-size disparity in the lateral geniculate nucleus (LGN) was amplified. With the addition of REM deprivation during MD, the LGN cells connected to the surgically patched eye, which are smaller than normal after MD, became even smaller, whereas the LGN cells receiving input from the seeing eye, which display compensatory hypertrophy after MD, grew even larger. We believe that the interlaminar disparity effect widened because during REM deprivation, the already vision-compromised LGN cells associated with the patched eye also lose the ascending brainstem activation reaching them during the REM state. Loss of the two main sources of 'afference' by these LGN cells permits their seeing-eye LGN counterparts to gain even greater advantage in the competition for synaptic connections in cortex, which is reflected in the relative soma sizes of the LGN relay cells. It is likely that the relatively abundant REM state in early maturation provides symmetric stimulation to all LGN relay cells, irrespective of eye of innervation. The symmetric activation propagated from brainstem to LGN acts to 'buffer' abnormal, asymmetric visual input and, thereby diminishes the extreme, asymmetric structural alteration that results from MD in the absence of REM sleep. We conclude that REM sleep-generated CNS discharge in development has the effect of 'protecting' the CNS against excessive plasticity changes. This is consistent with the possibility that REM sleep plays a role in the genetically programmed processes that direct normative brain development.

Essential and secondary hypertension and sleep-disordered breathing: a unifying hypothesis.

Obstructive sleep apnea (OSA) is a disorder in which there is repetitive collapse and closing of the pharynx during sleep. There is growing evidence to suggest that this disorder is a major cause of essential hypertension (EH) and that successful treatment of OSA can reduce the blood pressure (BP) significantly. In addition many other patients with EH have milder forms of sleep related breathing disorders (SRBD) like snoring, and upper airway resistance syndrome (UARS) which, while not as severe as OSA, may be severe enough to also cause systemic hypertension. We therefore propose a unifying hypothesis-that many patients with EH may have sleep related breathing disturbances (SRBD) and treatment of these disorders may improve the BP. SRBD could also explain many of the epidemiological, clinical, hereditary, biochemical, hematological and physiological characteristics seen in EH. In addition, many types of secondary hypertension (those caused by excessive alcohol intake, chronic renal failure, diabetes, hypothyroidism or acromegaly) have a higher than normal prevalence of OSA and OSA may contribute to the hypertension and organ damage found in these conditions as well. Thus SRBD may play an important role in the production of many cases of essential and secondary hypertension, and their early detection and treatment could reduce the hypertension and organ damage seen in these conditions.

Avoiding the supine position during sleep lowers 24 h blood pressure in obstructive sleep apnea (OSA) patients.

Obstructive sleep apnea (OSA), is a common clinical condition affecting at least 2-4% of the adult population. Hypertension is found in about half of all OSA patients, and about one-third of all patients with essential hypertension have OSA. There is growing evidence that successful treatment of OSA can reduce systemic blood pressure (BP). Body position appears to have an important influence on the incidence and severity of these sleep-related breathing disturbances. We have investigated the effect of avoiding the supine position during sleep for a 1 month period on systemic BP in 13 OSA patients (six hypertensives and seven normotensives) who by polysomnography (PSG) were found to have their sleep-related breathing disturbances mainly in the supine position. BP monitoring was performed by 24-h ambulatory BP measurements before and after a 1 month intervention period. We used a simple, inexpensive method for avoiding the supine posture during sleep, namely the tennis ball technique. Of the 13 patients, all had a reduction in 24-h mean BP (MBP). The mean 24-h systolic/diastolic (SBP/DBP) fell by 6.4/2.9 mm Hg, the mean awake SBP/DBP fell by 6.6/3.3 mm Hg and the mean sleeping SBP/DBP fell by 6.5/2.7 mm Hg, respectively. All these reductions were significant (at least P < 0.05) except for the sleeping DBP. The magnitude of the fall in SBP was significantly greater in the hypertensive than in the normotensive group for the 24 h period and for the awake hours. In addition, a significant reduction in BP variability and load were found. Since the majority of OSA patients have supine-related breathing abnormalities, and since about a third of all hypertensive patients have OSA, avoiding the supine position during sleep, if confirmed by future studies, could become a new non-pharmacological form of treatment for many hypertensive patients.