Giora Pillar

Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment.

OBJECTIVES To investigate the occurrence of nocturnal ischemic events in patients with obstructive sleep apnea syndrome (OSAS) and ischemic heart disease (IHD). BACKGROUND Although previous reports documented nocturnal cardiac ischemic events among OSAS patients, the exact association between obstructive apneas and ischemia is not yet clear. It is also not known what differentiates between patients showing nocturnal ischemia and those that do not. METHODS Fifty-one sleep apnea patients (age 61.3+/-8.3) with IHD participated in the study (after withdrawal of beta-adrenergic blocking agents and anti-anginotic treatment). All patients underwent whole-night polysomnography including ambulatory blood pressure recordings (30 min interval) and continuous Holter monitoring during sleep. A control group of 17 OSAS patients free from IHD were also similarly studied. Fifteen of the 51 patients were also recorded under continuous positive airway pressure (CPAP). RESULTS Nocturnal ST segment depression occurred in 10 patients (a total of 15 events, 182 min), of whom six also had morning ischemia (06-08 am). Five additional patients had only morning ischemia. No ischemic events occurred in the control group. Age, sleep efficiency, oxygen desaturation, IHD severity and nocturnal-double product (DP) values were the main variables that significantly differentiated between patients who had ischemic events during sleep and those who did not. Nocturnal ischemia predominantly occurred during the rebreathing phase of the obstructive apneas, and it is characterized by increased heart rate (HR) and DP values. Treatment with continuous positive airway pressure significantly ameliorated the nocturnal ST depression time from 78 min to 33 min (p<0.001) as well as the maximal DP values (14,137+/-2,827 vs. 12,083+/-2,933, p<0.001). CONCLUSIONS Exacerbation of ischemic events during sleep in OSAS may be explained by the combination of increased myocardial oxygen consumption as indicated by increased DP values and decreased oxygen supply due to oxygen desaturation with peak hemodynamic changes during the rebreathing phase of the obstructive apnea. Treatment with CPAP ameliorated the nocturnal ischemia.

Abdominal Fat and Sleep Apnea: the Chicken or the Egg?

Obstructive sleep apnea (OSA) syndrome is a disorder characterized by repetitive episodes of upper airway obstruction that occur during sleep. Associated features include loud snoring, fragmented sleep, repetitive hypoxemia/hypercapnia, daytime sleepiness, and cardiovascular complications. The prevalence of OSA is 2–3% and 4–5% in middle-aged women and men, respectively. The prevalence of OSA among obese patients exceeds 30%, reaching as high as 50–98% in the morbidly obese population. Obesity is probably the most important risk factor for the development of OSA. Some 60–90% of adults with OSA are overweight, and the relative risk of OSA in obesity (BMI >29 kg/m2) is ≥10. Numerous studies have shown the development or worsening of OSA with increasing weight, as opposed to substantial improvement with weight reduction. There are several mechanisms responsible for the increased risk of OSA with obesity. These include reduced pharyngeal lumen size due to fatty tissue within the airway or in its lateral walls, decreased upper airway muscle protective force due to fatty deposits in the muscle, and reduced upper airway size secondary to mass effect of the large abdomen on the chest wall and tracheal traction. These mechanisms emphasize the great importance of fat accumulated in the abdomen and neck regions compared with the peripheral one. It is the abdomen much more than the thighs that affect the upper airway size and function. Hence, obesity is associated with increased upper airway collapsibility (even in nonapneic subjects), with dramatic improvement after weight reduction. Conversely, OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. OSA is associated with increased sympathetic activation, sleep fragmentation, ineffective sleep, and insulin resistance, potentially leading to diabetes and aggravation of obesity. Furthermore, OSA may be associated with changes in leptin, ghrelin, and orexin levels; increased appetite and caloric intake; and again exacerbating obesity. Thus, it appears that obesity and OSA form a vicious cycle where each results in worsening of the other.

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function.

BACKGROUND Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.

Cardiovascular Complications of Obstructive Sleep Apnea Syndrome : Evidence from Children

Obstructive Sleep Apnea Syndrome (OSAS) is a common condition in children, and is characterized by intermittent partial or complete occlusion of the upper airway during sleep, leading to profound disturbances in homeostatic gas exchange, frequent arousals and disturbed sleep architecture. Pediatric OSAS is associated with a multitude of end-organ morbidities, most of which have been uncovered in the last decade. Of particular interest are the cardiovascular complications that may develop in children with OSAS, since they are posited to have not only an immediately significant impact on cardiovascular health during childhood, but may also affect cardiovascular outcomes later during adult life. In this review, we will present the specific cardiovascular complications that have thus far been described in children with OSAS, with reference to pertinent mechanisms, and potential implications.

Long-term sleep disturbances in adolescents after minor head injury

It has been demonstrated that patients in the acute phase after minor head injury (MHI) complain of sleep disturbances. The purpose of the present study was to characterize the long-term effects of MHI on sleep in adolescents. Nineteen adolescents who had suffered MHI 3 years before the study and had complained of sleep disturbances completed a sleep questionnaire and were investigated in the sleep laboratory by whole-night polysomnographic recordings and were actigraphically monitored for 5 days at home. Questionnaire results revealed severe complaints regarding sleep behavior. Polysomnographic recordings revealed that in comparison with controls, MHI was associated with lower sleep efficiency (79.8 +/- [9.8]% vs 87.7 +/- [6.8]%; P < 0.005), with more wake time (10.6 +/- [9.0]% vs 3.4 +/- [4.4]%; P < 0.005), and with more awakenings lasting more than 3 minutes (2.1 +/- [1.5] vs 0.6 +/- [0.8]; P < 0.005). These findings were confirmed by actigraphic monitoring that revealed lower sleep efficiency (90 +/- [5]% vs 94 +/- [3]%; P < 0.05), more minutes of wake time (49 +/- [21] min vs 28 +/- [15] min; P < 0.05), and a trend toward more awakenings longer than 5 minutes (1.8 +/- [0.8] vs 1.2 +/- [0.8]; P = 0.063). Our data demonstrated that 3 years after MHI without any discernible clinical sequel, adolescents still complain of sleep disturbances that could be confirmed by both polysomnographic and actigraphic monitoring.

Melatonin effect on seizures in children with severe neurologic deficit disorders.

Summary:  Purpose: Recently, melatonin has been associated with antiepileptic activity, most probably because of its antioxidant activity as a free radical scavenger. This study aimed to expand the clinical experience with melatonin as an antiepileptic drug (AED) in humans.

Pre-eclampsia is associated with sleep- disordered breathing and endothelial dysfunction

Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4±8.4 versus 8.3±1.3·h−1, and 1.5±0.1 versus 1.8±0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study.

Sublingual electrical stimulation of the tongue during wakefulness and sleep.

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.

Contributions of hypoxia and respiratory disturbance index to sympathetic activation and blood pressure in obstructive sleep apnea syndrome

Hypertension is a common finding among obstructive sleep apnea (OSA) patients, and is thought to be caused by sympathetic hyperactivity. The present study compares the contributions of the respiratory disturbance index (RDI) as a reflection of sleep fragmentation, and the magnitude of oxygen desaturation, to sympathetic activation as indexed by urinary norepinephrine concentrations, as well as to morning and evening blood pressure in sleep apnea syndrome patients. Data (polysomnography, blood pressure [BP], and urine catecholamines) of 38 consecutive OSA patients (age, 46+/-14.5 years) were analyzed. Stepwise logistic regression analysis revealed that minimal oxygen saturation level (SaO2min) was a significant predictor of both morning and evening norepinephrine levels, and that 37% of morning systolic BP variance could be accounted for by a combination of age and norepinephrine, while 20% of the diastolic BP variance was accounted for by SaO2min alone. In contrast, RDI entered the prediction equation only when minimal oxygen saturation was rejected first. Our results indicate that the degree of nocturnal hypoxia is more closely associated with the level of sympathetic activation and with daytime level of blood pressure than with sleep fragmentation.

Melatonin improves sleep-wake patterns in psychomotor retarded children

Five children with severe psychomotor retardation (mean age 8.2+/-3.6 years) and irregular sleep-wake patterns underwent 1 week of wrist actigraphic monitoring before and after treatment with 3 mg melatonin. Three underwent multiple measurements of urinary sulfatoxymelatonin levels. Urine sulfatoxymelatonin levels were abnormally low, without any significant day/night differences. Melatonin treatment increased nighttime sleep from 5.9+/-0.8 to 7.3+/-0.5 hours (paired t test, P<0.01) and sleep efficiency from 69.3%+/-6.2% to 88.3%+/-2.3% (P<0.01). Daytime sleep decreased from 3.2+/- 1.2 to 1.7+/-1.2 hours (P<0.05). Thus, no change in 24-hour total sleep time (9.1+/-1.5 vs. 9.0+/-1.6 hours) occurred. Administration of 3 mg melatonin to five severely psychomotor retarded children resulted in a significant improvement in their sleep-wake patterns.