OBJECTIVETo evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea.METHODSThirteen male patients with severe obstructive sleep apnea (mean age 43±10 years with a mean body mass index of 26.7±1.9 kg/m2) received a single 50-mg dose of sildenafil or a placebo at bedtime. All-night polysomnography and heart rate variability were recorded. Frequency domain analysis of heart rate variability was performed for the central five-minute sample of the longest uninterrupted interval of slow wave and rapid eye movement sleep, as well as for one-minute samples during apnea and during slow wave and rapid eye movement sleep after resumption of respiration.RESULTSCompared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HFnu) components and a decrease in the low/high-frequency components of the heart rate variability ratio (LF/HF) in slow wave sleep (p<0.01 for both). Differences in heart rate variability parameters between one-minute post-apnea and apnea samples (Δ = difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of ΔLF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, ΔLF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (sR = −0.72 and −0.51, respectively, p= 0.01 for both), and ΔHFnu in rapid eye movement sleep was correlated with mean desaturation (sR= 0.66, p= 0.02) and the desaturation index (sR= 0.58, p = 0.047).CONCLUSIONSThe decrease in arousal response to apnea/hypopnea events along with the increase in HFnu components and decrease in LH/HF components of the heart rate variability ratio during slow wave sleep suggest that, in addition to worsening sleep apnea, sildenafil has potentially immediate cardiac effects in patients with severe obstructive sleep apnea.

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4609 Background In last decade, there has been growing research in sleep disorders associated with sickle cell disease (SCD), particularly focusing on oxyhemoglobin desaturation. The coexistence of periodic limb movement (PLM) and anemia is well known, however it remains controversial to which extent dopamine deficiency, lower serum ferritin levels or iron deficiency contribute to the pathophysiology of PLM in anemia. Objective The aim of this study is to evaluate the relationship between PLM and other manifestations of SCD Methods Eight male patients with SCD were age and BMI-matched to 16 healthy controls (1:2) for sleep evaluation by clinical inventory and polysomnography (PSG). PLMS were defined as limbs movements lasting 0.5–5 seconds that recur every 5 to 90 seconds in a series of ≥ 4. Serum levels of ferritin and hemoglobin were assessed. Results Comparing to controls (aged 28.6 ±5.9 yrs, BMI of 22.1 ±3.8 kg/m2), SCD patients (aged 28.0 ±7.3 yrs, BMI of 21.4 ±4.6 kg/m2 p>0.05, both) scored their sleep satisfaction as moderate (75% vs. 12.5%, p=0.005), whereas 50% of controls scored it as very satisfactory (vs. none of the SCD patients, p=0.02). Awakenings in the middle of the night were frequently reported by SCD patients (87.5% vs. 43.7%, p= 0.05) as well as pain complaints (87.5% vs. 37.5%, p=0.03). PSG data revealed that, compared to controls, SCD patients exhibited decrease in sleep efficiency (76.7% ±12.6 vs. 87.9% ±4.8, p=0.004), in REM sleep percentage (10.6 % ±6.0 vs. 20.3% ±5.8, p=0.001), and increase in wake after sleep onset (65.3%±38.9 vs. 32.4% ±20.2, p=0.012), arousal index (16.3/hour ±8.5 vs. 9.5/hour ±4.9, p=0.021), PLM index (13.1 ±10.1 vs. 2.8 ±3.3, p= 0.001), apnea hypopnea index (8.8/hour ±5.6 vs. 3.4/hour ±5.0, p=0.025). Lower mean oxyhemoglobin saturation (88.0 mmHg ±3.4 vs. 92.4 mmHg ±5.4, p=0.049), and hemoglobin levels (8.7g/dl ±1.1 vs. 15.8g/dl ±0.7, p<0.001) were also verified in SCD patients. Interestingly, ferritin levels did not differ between groups (209.6±132.8 in SCD patients vs. 214.8 ±142.2, p=0.949). Linear regression showed that SCD condition represented an independent risk feature for PLM (R2 = 0.51, p<0.001). Correlation between PLM and the number of comorbities related to SCD was substantial (r=0.79, p=0.02) Conclusions Subjective sleep complaints reported by patiens with SCD were supported by PSG findings of sleep disruption and lower mean oxyhemoglobin saturation. Increase in PLM in SCD patients correlated the number of comorbities of the disease. In contrast with the literature, ferritin did not play a role in the pathophysiology of PLM in these patients. This study was supported by FAPESP CEPID 98/14303-3 and AFIP Disclosures: No relevant conflicts of interest to declare.