A prospective cohort study of the long-term effects of CPAP on carotid artery intima-media thickness in Obstructive sleep apnea syndrome

Objective

To examine the long-term effect of CPAP on carotid artery intima-media thickness (IMT) in patients with Obstructive sleep apnea syndrome(OSAS).

Methods

A prospective observational study over 12 months at a teaching hospital on 50 patients newly diagnosed with OSAS who received CPAP or conservative treatment (CT). Carotid IMT was assessed with B-mode Doppler ultrasound from both carotid arteries using images of the far wall of the distal 10 mm of the common carotid arteries at baseline, 6 months and 12 months.

Measurements and results [mean (SE)]

Altogether 28 and 22 patients received CPAP and CT respectively without significant differences in age 48.8(1.8) vs 50.5(2.0)yrs, BMI 28.2(0.7) vs 28.0(1.2)kg/m2, ESS 13.1(0.7) vs 12.7(0.6), AHI 38(3) vs 39(3)/hr, arousal index 29(2) vs 29(2)/hr, minimum SaO₂ 75(2) vs 77(2)% and existing co-morbidities. CPAP usage was 4.6(0.3) and 4.7(0.4)hrs/night over 6 months and 1 year respectively. Carotid artery IMT at baseline, 6 months, and 12 months were 758(30), 721(20), and 705(20)micron for the CPAP group versus 760(30), 770(30), and 778(30)micron respectively for the CT group, p = 0.002.Among those free of cardiovascular disease(n = 24), the carotid artery IMT at baseline, 6 months and 12 months were 722(40), 691(40), and 659(30)micron for the CPAP group (n = 12) with usage 4.5(0.7) and 4.7(0.7) hrs/night over 6 months and 12 months whereas the IMT data for the CT group(n = 12) were 660(20), 685(10), and 690(20)micron respectively, p = 0.006.

Conclusions

Reduction of carotid artery IMT occurred mostly in the first 6 months and was sustained at 12 months in patients with reasonable CPAP compliance.     

Day-night variations of serum interleukin-6 in patients with severe obstructive sleep apnea syndrome before and after continuous positive airway pressure (CPAP)

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin-6 (IL-6) is one of the important proinflammatory cytokines. We examined the levels of serum IL-6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL-6 levels were significantly reduced after CPAP therapy by 46% (6.2+/-1.0 vs. 3.3+/-0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL-6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL-6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL-6 in severe OSAS patients.     

Early detection of upper airway obstructions by analysis of acoustical respiratory input impedance

Repetitive occurrence of partial or total upper airway obstruction characterizes several respiratory dysfunctions such as the obstructive sleep apnea syndrome (OSAS). In OSAS patients, pharyngeal collapses are linked to a decrease in upper airway muscle activity during sleep which causes decreased upper airway wall stiffness. Continuous positive airway pressure (CPAP) is recommended as the treatment of choice. Advancements in CPAP therapy require early detection of respiratory events in real time to adapt the level of the applied pressure to airway collapsibility. The forced oscillation technique (FOT) is a noninvasive method which reflects patients' airway patency by measuring respiratory impedance. The aim of this study was to evaluate by a mathematical model of the respiratory system if FOT can provide an early detection index of total or partial upper airway obstruction. Furthermore, the simulation should suggest which characteristic features are relevant for early apnea detection in measured clinical data. The respiratory system has been treated as a series of cylindrical segments. The oropharynx analog of the model allows simulation of upper airway collapse, mimicking the situation in patients with OSAS. We calculated the input impedance for different degrees of upper airway obstruction ranging from unobstructed airways to total occlusion. Furthermore, we simulated different upper airway wall compliances. We compared the simulation with real data. The results of the study suggest that FOT is a valuable tool for assessing the degree of upper airway obstruction in patients with OSAS. Especially, the phase angle of the impedance seems to be a potentially useful tool for early apnea detection by assessing the upper airway wall collapsibility. Received: 23 July 1998 / Accepted in revised form: 26 January 1999     

Financial incentive increases CPAP acceptance in patients from low socioeconomic background

Objective

We explored whether financial incentives have a role in patients′ decisions to accept (purchase) a continuous positive airway pressure (CPAP) device in a healthcare system that requires cost sharing.

Design

Longitudinal interventional study.

Patients

The group receiving financial incentive (n = 137, 50.8±10.6 years, apnea/hypopnea index (AHI) 38.7±19.9 events/hr) and the control group (n = 121, 50.9±10.3 years, AHI 39.9±22) underwent attendant titration and a two-week adaptation to CPAP. Patients in the control group had a co-payment of $330–660; the financial incentive group paid a subsidized price of $55.

Results

CPAP acceptance was 43% greater (p = 0.02) in the financial incentive group. CPAP acceptance among the low socioeconomic strata (n = 113) (adjusting for age, gender, BMI, tobacco smoking) was enhanced by financial incentive (OR, 95% CI) (3.43, 1.09–10.85), age (1.1, 1.03–1.17), AHI (>30 vs. <30) (4.87, 1.56–15.2), and by family/friends who had positive experience with CPAP (4.29, 1.05–17.51). Among average/high-income patients (n = 145) CPAP acceptance was affected by AHI (>30 vs. <30) (3.16, 1.14–8.75), living with a partner (8.82, 1.03–75.8) but not by the financial incentive. At one-year follow-up CPAP adherence was similar in the financial incentive and control groups, 35% and 39%, respectively (p = 0.82). Adherence rate was sensitive to education (+yr) (1.28, 1.06–1.55) and AHI (>30 vs. <30) (5.25, 1.34–18.5).

Conclusions

Minimizing cost sharing reduces a barrier for CPAP acceptance among low socioeconomic status patients. Thus, financial incentive should be applied as a policy to encourage CPAP treatment, especially among low socioeconomic strata patients.     

Long-term facilitation in obstructive sleep apnea patients during NREM sleep.

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 +/- 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4-6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O(2) fraction (FI(O(2))) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing (n = 11), and supraglottic pressure (n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 +/- 8% of control), despite decreased Rua to 58 +/- 24% of control (P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.     

Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial

Objective

This study aimed to examine the effects of carbocysteine in OSAS patients.

Methods

A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group.

Results

The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18±4.28 vs. 6.82±3.66; P≤0.01), apnea-hypopnea index (55.34±25.03 vs. 47.56±27.32; P≤0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P≤0.01), and lowest oxygen saturation level (65.88±14.86 vs. 70.41±14.34; P≤0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71±0.15 vs. 0.66±0.15; P≤0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group.

Conclusions

Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02015598","term_id":"NCT02015598"}}NCT02015598     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Day‐Night Variations of Serum Interleukin‐6 in Patients with Severe Obstructive Sleep Apnea Syndrome before and after Continuous Positive Airway Pressure (CPAP)

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin‐6 (IL‐6) is one of the important proinflammatory cytokines. We examined the levels of serum IL‐6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL‐6 levels were significantly reduced after CPAP therapy by 46% (6.2±1.0 vs. 3.3±0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL‐6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL‐6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL‐6 in severe OSAS patients.     

Reliability of home CPAP titration with different automatic CPAP devices

Background

CPAP titration may be completed by automatic apparatus. However, differences in pressure behaviour could interfere with the reliability of pressure recommendations. Our objective was to compare pressure behaviour and effective pressure recommendations between three Automatic CPAP machines (Autoset Spirit, Remstar Auto, GK 420).

Methods

Sixteen untreated obstructive sleep apnea patients were randomly allocated to one of the 3 tested machines for a one-week home titration trial in a crossover design with a 10 days washout period between trials.

Results

The median pressure value was significantly lower with machine GK 420 (5.9 +/- 1.8 cm H₂O) than with the other devices both after one night and one week of CPAP titration (7.4 +/- 1.3 and 6.6 +/- 1.9 cm H₂O). The maximal pressure obtained over the one-week titration was significantly higher with Remstar Auto (12.6 +/- 2.4 cm H₂O, Mean +/- SD) than with the two other ones (10.9 +/- 1.0 and 11.0 +/- 2.4 cm H₂O). The variance in pressure recommendation significantly differed between the three machines after one night and between Autoset Spirit and the two other machines after 1 week.

Conclusion

Pressure behaviour and pressure recommendation significantly differ between Auto CPAP machines both after one night and one week of home titration.     

Chronic continuous positive airway pressure (CPAP) reduces airway reactivity in vivo in an allergen-induced rabbit model of asthma

Previous studies have demonstrated that chronic mechanical strain produced by continuous positive airway pressure (CPAP) reduces in vivo airway reactivity in rabbits and ferrets. For CPAP to potentially have a therapeutic benefit for asthmatic subjects, the reduction in airway responsiveness would need to persist for 12-24 h after its discontinuation, require application for only part of the day, and be effective in the presence of atopic airway inflammation. In the present study, airway responsiveness to acetylcholine or methacholine was measured during mechanical ventilation following three different protocols in which active, nonanesthetized, tracheotomized rabbits were treated with High vs. Low CPAP (6 vs. 0 cmH(2)O). 1) High CPAP was applied continuously for 4 days followed by 1 day of Low CPAP; 2) High CPAP was applied at night and Low CPAP during the daytime for 4 days, and 3) High CPAP was applied for 4 days in animals following ovalbumin (Ova) sensitization and challenge. For all three protocols, treatment with High CPAP resulted in significantly reduced airway responsiveness compared with treatment with Low CPAP. Cumulatively, our in vivo results in rabbits suggest that high CPAP, even when applied only at night, produces a persistent reduction of airway responsiveness. In addition, CPAP reduces airway responsiveness even in the presence of atopic airway inflammation.     

Vanished Gender Differences of Cardiometabolic Risk Factors After Matching the Apnea Hypopnea Index at Postmenopausal Age

BackgroundSleep-disordered breathing (SDB) and cardiometabolic risk factors are male prevalent.ObjectiveThis study investigated whether gender differences remained prominent after matching for the apnea hypopnea index (AHI) and postmenopause.MethodsIn a retrospective analysis of 350 eligible SDB patients, female patients were matched with male patients of the same age and body mass index (BMI) (age-BMI-matched [nAHImt]; n = 102 pairs) or were matched with male patients of the same age, BMI, and AHI (age-BMI-AHI-matched [AHImt]; n = 66 pairs). The nAHImt or AHImt patients were further separated into junior and senior subgroups.ResultsIn the nAHImt/junior group, women had shorter neck circumferences, better sleep architecture, and lower AHI, Epworth Sleepiness Scale (ESS) score, blood pressure (BP), total cholesterol (TC), triglyceride (TG), and uric acid (UA) than nAHImt/junior men. In the AHImt/junior group, women had shorter neck circumferences, lower waist/hip ratios, ESS, BP, TG, and UA than AHImt junior men. In the nAHImt/senior group, women had lower AHI, neck circumferences, waist/hip ratios, diastolic BP, and UA than men. In contrast, in the AHImt/senior group, most cardiometabolic parameters were similar between women and men. After further matching for the AHI, many elements of gender differences disappeared.ConclusionsCompared with AHImt men, women had lower UA, TG, BP, and daytime sleepiness before menopause, but gender differences became indistinguishable postmenopause. We suggested that matching sleep quality or adjusting AHI would be noteworthy and required for studying gender differences.     

Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients

Background

Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.

Methods

Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H₂0) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.

Results

8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).

Conclusion

Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP.     

α1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat

To determine which subtype of α₁-adrenergic receptors plays a role in the regulation of blood pressure, with α_1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various α₁-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED₅₀, Dr) of α₁-adrenoceptor selective antagonist (prazosin, Dr 13.5 ± 3.6 vs.15.1 ± 4.3, n = 11), α_1A-adrenoceptor selective antagonist (5-methyl-urapidil, Dr 2.4 ± 0.9 vs. 3.7 ± 2.3, n = 12; RS-17053, Dr 3.2 ± 1.6 vs. 4.4 ± 3.3, n = 12) and α_1D-adrenoceptor selective antagonist (BMY7378, Dr 1.9 ± 0.9 vs. 2.2 ± 0.8, n = 8) on phenylephrine-induced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial blood pressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4 ± 0.6 vs. 4.3 ± 0.9, n = 5; BMY7378, Dr 1.7±0.5 vs. 1.7 ± 0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by α_1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.     

Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment

Introduction

Obstructive Sleep Apnea (OSA) is a major risk factor for cardiovascular disease. The goal of this study was to demonstrate whether the use of CPAP produces significant changes in the heart rate or in the heart rate variability of patients with OSA in the first night of treatment and whether gender and obesity play a role in these differences.

Methods

Single-center transversal study including patients with severe OSA corrected with CPAP. Only patients with total correction after CPAP were included. Patients underwent two sleep studies on consecutive nights: the first night a basal study, and the second with CPAP. We also analyzed the heart rate changes and their relationship with CPAP treatment, sleep stages, sex and body mass index. Twenty-minute segments of the ECG were selected from the sleep periods of REM, no-REM and awake. Heart rate (HR) and heart rate variability (HRV) were studied by comparing the R-R interval in the different conditions. We also compared samples from the basal study and CPAP nights.

Results

39 patients (15 females, 24 males) were studied. The mean age was 50.67 years old, the mean AHI was 48.54, and mean body mass index was 33.41 kg/m² (31.83 males, 35.95 females). Our results showed that HRV (SDNN) decreased after the use of CPAP during the first night of treatment, especially in non-REM sleep. Gender and obesity did not have any influence on our results.

Conclusions

These findings support that cardiac variability improves as an acute effect, independently of gender or weight, in the first night of CPAP use in severe OSA patients, supporting the idea of continuous use and emphasizing that noncompliance of CPAP treatment should be avoided even if it is just once.     

Novel Approach to Simulate Sleep Apnea Patients for Evaluating Positive Pressure Therapy Devices

Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients’ characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient’s night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment.     

Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy

Increased cardiac output in pregnancy is associated with cardiac remodeling and possible reduction in contractility, which may worsen in preeclampsia. Left ventricular (LV) geometry and function were compared between nonpregnant controls (n = 12) and normotensive (n = 44) and preeclamptic (n = 15) pregnant women using echocardiography. Load-independent comparisons of LV systolic function compared end-systolic stress (ESS) and rate-corrected velocity of circumferential fiber shortening (V(CFC)). Mean arterial pressures were 101 +/- 14 mmHg in preeclampsia, 76 +/- 6 mmHg in normotensive pregnancy, and 78 +/- 6 mmHg in controls (P < 0.005 vs. preeclampsia). LV mass increased during normotensive pregnancy (66 +/- 13 to 76 +/- 16 g/m(2); P < 0.05; controls, 65 +/- 10 g/m(2); P < 0.05) and was greater in preeclampsia (90 +/- 18 g/m(2); P < 0.05). In normotensive pregnancy, ESS decreased (59 +/- 9 to 52 +/- 11 g/cm(2); P < 0.05; controls, 66 +/- 14 g/cm(2); P < 0.005). ESS was greater in preeclampsia (60 +/- 14 g/cm(2); P < 0.05). In controls, there was an inverse relationship between ESS and V(CFC) (r = -0.78). The ESS-V(CFC) relationships in normotensive and preeclamptic pregnancy were unchanged from controls. We conclude that LV hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac work, and LV contractility is preserved.     

Heat extraction through the palm of one hand improves aerobic exercise endurance in a hot environment.

In situations where the accumulation of internal heat limits physical performance, enhanced heat extraction from the body should improve performance capacity. The combined application of local subatmospheric pressure (35-45 mmHg) to an entire hand (to increase blood volume) and a heat sink (18-22 degrees C) to the palmar surface were used to draw heat out of the circulating blood. Subjects walked uphill (5.63 km/h) on a treadmill in a 40 degree C environment. Slopes of the treadmill were held constant during paired experimental trials (with and without the device). Heat extraction attenuated the rate of esophageal temperature rise during exercise (2.1 +/- 0.4 degrees and 2.9 +/- 0.5 degrees C/h, mean +/- SE, with and without the device, respectively; n = 8) and increased exercise duration (46.1 +/- 3.4 and 32.3 +/- 1.7 min with and without the device, respectively; n = 18). Hand cooling alone had little effect on exercise duration (34.1 +/- 3.0, 38.0 +/- 3.5, and 57.0 +/- 6.4 min, for control, cooling only, and cooling, and subatmospheric pressure, respectively; n = 6). In a longer term study, nine subjects participated in two or four trials per week for 8 wk. The individual workloads (treadmill slope) were varied weekly. Use of the device had a beneficial effect on exercise endurance at all workloads, but the benefit proportionally decreased at higher workloads. It is concluded that heat can be efficiently removed from the body by using the described technology and that such treatment can provide a substantial performance benefit in thermally stressful conditions.     

Challenging the sleep homeostat does not influence the thermoregulatory system in men: evidence from a nap vs. sleep-deprivation study

The purpose of our study was to understand the relationship between the components of the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) and the thermoregulatory system. This was achieved by comparing the impact of a 40-h sleep deprivation vs. a 40-h multiple nap paradigm (10 cycles with 150/75 min wakefulness/sleep episodes) on distal and proximal skin temperatures, core body temperature (CBT), melatonin secretion, subjective sleepiness, and nocturnal sleep EEG slow-wave activity in eight healthy young men in a "controlled posture" protocol. The main finding of the study was that accumulation of sleep pressure increased subjective sleepiness and slow-wave activity during the succeeding recovery night but did not influence the thermoregulatory system as measured by distal, proximal, and CBT. The circadian rhythm of sleepiness (and proximal temperature) was significantly correlated and phase locked with CBT, whereas distal temperature and melatonin secretion were phase advanced (by 113 +/- 28 and 130 +/- 30 min, respectively; both P < 0.005). This provides evidence for a primary role of distal vasodilatation in the circadian regulation of CBT and its relationship with sleepiness. Specific thermoregulatory changes occur at lights off and on. After lights off, skin temperatures increased and were most pronounced for distal; after lights on, the converse occurred. The decay in distal temperature (vasoconstriction) was significantly correlated with the disappearance of sleep inertia. These effects showed minor and nonsignificant circadian modulation. In summary, the thermoregulatory system seems to be independent of the sleep homeostat, but the circadian modulation of sleepiness and sleep inertia is clearly associated with thermoregulatory changes.     

Daytime Sleepiness in Parkinson’s Disease: A Reappraisal

Background

Excessive daytime sleepiness is a frequent complaint in Parkinson’s disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson’s disease (PD) using a wide range of potential predictors.

Methods

One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.

Results

Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.

Conclusion

We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.