Original ArticleThe effect of sildenafil on sleep respiratory parameters and heart rate variability in obstructive sleep apnea
Introduction
A concern regarding the increasing percentage of men using selective phosphodiesterase-5 (PDE-5) inhibitor drugs to treat erectile dysfunction [1] is justified by the magnifying effect of sildenafil on the respiratory events in severe OSA, as previously demonstrated by our group [2]. In this previous study we speculated that nasal congestion, frequently reported by sildenafil users [3], may underlie the increase in number and duration of obstructive respiratory events. In addition, ventilation–perfusion mismatch may be attributed to the nitric oxide (NO)-dependent pulmonary vasodilatory effect of sildenafil, occurring in the absence of ventilation, with consequent enhancement in oxyhemoglobin desaturation. Besides a deleterious impact of NO-increased bioavailability on hemodynamic parameters in severe OSA, the decrease in percentage of SWS after sildenafil, in comparison to placebo, might evidence OSA severity, as has been proposed by other authors [4], [5], [6].
Clinically, OSA is very much a REM-sleep related disease [7], however, the degree of sleep synchronization also influences the magnitude of hypoxemia, intensity of upper airway occlusion, and arousability [8], [9]. The low synchronization of REM sleep contrasts with the highly synchronized slow wave sleep (SWS, defined as the sum of non-REM sleep stages 3 and 4) also in terms of impact on heart frequency. Taking into account the influence of sleep stage and respiration on HRV, this study was conducted with the aim to evaluate to which extent the NO-mediated effects of sildenafil act upon respiratory and HRV parameters in SWS and REM sleep. The primary endpoint was to separately assess central and obstructive respiratory events and the distribution of arousals in both non-REM and REM sleep. As a second outcome, HRV parameters were analyzed in apnea-free samples during SWS and REM sleep.
Section snippets
Methods
The present study is an extension of an earlier project and was conducted based on experimental data obtained from 13 patients prospectively enrolled in our previous double-blind, randomized, controlled study on the effect of sildenafil in sleep parameters in severe OSA [2].
Details of the study design, sampling plan, and methodology have been reported elsewhere [2]. In brief, 13 of 49 middle-aged men with OSA consecutively recruited for this study were selected (age 53.1 ± 9.8 years, BMI 26.7 ± 1.9
Results
The 13 studied patients were evaluated during sleep after placebo or sildenafil 50 mg by means of polysomnography and HRV simultaneously recorded. Some of the results of the present study have been reported previously [2].
Comparison of apnea–hypopnea index per hour of TST, non-REM sleep time and REM sleep between placebo and sildenafil are illustrated in Fig. 1. The increase in AHI (central plus obstructive events) in TST after sildenafil, in comparison to placebo [mean ± SE (CIs), 48.1 ± 20.6
Discussion
The most important finding in this study is that in OSA patients, sildenafil increased apnea–hypopnea index not only as a whole, but also specifically in non-REM (central and obstructive events) and in REM sleep (obstructive events) compared to placebo. In addition to the previously described effect of sildenafil in decreasing SWS percentage and increasing desaturation index [2], the present results clarify that the lack in concomitant arousal enhancement may be attributed to the decreased
Conclusion
In conclusion, the present study not only confirms our findings that the use of sildenafil at bedtime plays a detrimental role in apnea events of severe OSA patients, but also demonstrates the extent of such effects on the cardiovascular system. Exacerbation of apnea in both non-REM and REM sleep, fragmentation in REM sleep, and a prolonged increase in LH/HF component of HRV after resumption of ventilation were observed in severe OSA patients after a single dose of sildenafil 50 mg at bedtime.
Acknowledgements
This study was supported by grants of CEPID-FAPESP, Sao Paulo, Brazil and Associação Fundo Incentivo a Psicofarmacologia. The authors would like to thank Mrs. Francisca Veloso for the support in all steps of this study.
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