Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea.
OBJECTIVE
To evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea.


METHODS
Thirteen male patients with severe obstructive sleep apnea (mean age 43+/-10 years with a mean body mass index of 26.7+/-1.9 kg/m(2)) 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.


RESULTS
Compared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HF(nu)) 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 (Delta = difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of DeltaLF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, DeltaLF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (s(R =) -0.72 and -0.51, respectively, p= 0.01 for both), and DeltaHF(nu) in rapid eye movement sleep was correlated with mean desaturation (s(R=) 0.66, p= 0.02) and the desaturation index (s(R=) 0.58, p = 0.047).


CONCLUSIONS
The decrease in arousal response to apnea/hypopnea events along with the increase in HF(nu) 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.
Neves
Christiane
C
Department of Psychobiology, Universidade Federal de São Paulo - São Paulo, Brazil. christianen1@hotmail.com
Tufik
Sérgio
S
Chediek
Felipe
F
Poyares
Dalva
D
Cintra
Fátima
F
Roizenblatt
Marina
M
Abrantes
Fabiano
F
Monteiro
Marina Ariza
MA
Roizenblatt
Suely
S
D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects*; D015992:Body Mass Index; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D017286:Polysomnography; D011687:Purines / Q000009:adverse effects / Q000494:pharmacology; D012119:Respiration; D000068677:Sildenafil Citrate; D012890:Sleep / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D012895:Sleep, REM / Q000187:drug effects; D013450:Sulfones / Q000009:adverse effects / Q000494:pharmacology*
D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
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