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/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. RESULTS: Compared 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, Δ LF/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 Δ HFnu 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). CONCLUSIONS: The 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.

Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS) in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage) to male Wistar rats (3 months old, 200-250 g) 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water) during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001). The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist) or atropine (cholinergic antagonist). These drugs were administered 1 h prior to ethanol (3.5 g/kg) or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Effect of SX-3228, a selective ligand for the BZ1 receptor, on sleep and waking during the light-dark cycle in the rat

The effects of the benzodiazepine1 (BZ1) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning of the light phase of the light-dark cycle induced a significant reduction of rapid-eye-movement sleep (REMS) during the third recording hour. Moreover, slow wave sleep (SWS) was increased during the fourth recording hour after the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the light-dark cycle caused a significant and maintained (6-h recording period) reduction of waking (W), whereas SWS and light sleep (LS) were increased. REMS values tended to increase during the entire recording period; however, the increase was statistically significant only for the 1.0 mg/kg dose during the first recording hour. In addition, a significant and dose-related increase of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX-3228 is a potent hypnotic when given to the rat during the dark period of the light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat

Comparative effects of hyoscine butylbromide and atropine sulphate on sleep architecture in healthy human volunteers.

The changes in sleep architecture, heart rate and respiratory rate to hyoscine butylbromide (HBB), a peripherally acting anticholinergic was studied. These effects were compared with that of atropine sulphate, a drug known to cross the blood brain barrier. The study followed a single blind cross over design with a one week washout period. Atropine sulphate (0.4 mg) and HBB (10 mg) were given intravenously to ten adult healthy male volunteers before sleep onset. Normal saline was used as control. All night sleep polysomnography was done with the standard montage for sleep staging. Respiration and airflow were also monitored. Rapid eye movement (REM) latency was significantly increased with both the drugs whereas the duration of REM sleep was decreased only with atropine. Slow wave sleep (SWS) was also increased significantly by atropine. There was no change in heart rate, or respiratory rate during any of the sleep stages. HBB affects the initiation of REM sleep whereas atropine affects both its initiation and maintenance.

Diagnóstico de transtorno afetivo por polissonografia / Diagnosis of affective disorders by polysomnography

Alteraçöes do sono constituem queixa frequente de pacientes psiquiátricos e o estudo do sono através da polissonografia é considerado a única janela neurobiológica para sondar transtornos psíquicos. Revisando-se a literatura, observou-se que os achados de pacientes com transtornos afetivos diferem significativamente do normal mais amiúde do que qualquer outra doença psiquiátrica. Embora a latência ao sono REM tenha alta sensiblildade e especificidade, nenhum achado da polissonografia pode ser considerado como patognomônico de distúrbio afetivo. Neste artigo, seräo revisados os padröes de sono relacionados com o distúrbio afetivo, sua sensibilidade e especificidade, seu valor na previsäo da resposta terapêutica e suas mudanças nas diferentes idades

Estudo da motilidade ocular no sono: o sono REM e suas implicaçöes oftalmológicas / Review of the ocular motility in sleep: the REM sleep and their phthalmologic implications

Este trabalho faz uma revisäo crítica relativa aos dois tipos de movimentos oculares, que ocorre durante o período do sono, com ênfase para os movimentos rápidos dos olhos ou REM (Rapid Eye Movements) . O autor tem como hipótese, que a inibiçäo dos movimentos rápidos dos olhos durante o Sono REM, possa beneficiar o prognóstico cirúrgico, principalmente em pacientes com ferimentos perfurantes do globo ocular. Com esse propósito foi sugerida uma metodologia com diversos parâmetros, incluindo o uso de substâncias inibitórias do REM. Os principais problemas surgidos durante a pesquisa säo comentados

Sueño REM del electroencefalograma como método diagnóstico de las depresiones enmascaradas: a propósito de 19 casos / REM sleep of electroencephalogram as diagnostic method of the masquerade depressions: apropos of 19 cases

Partiendo del conocimiento científico de que las depresiones endógenas, en un 98%, cursan con "disomnias", y que estas alteraciones del sueño son típicas y diferentes en insomnos comunes y en pacientes neuróticos, utilizamos como parámetro neurofisiológico, el Sueño REM del EEG. Buscamos la seguridad individual en el diagnóstico de depresión postsináptica (endógena o primaria), correlacionando nuestros hallazgos clínico-psicopatológicos (basados en la escuela de Weitbrecht y Kielholz) con la medición de la latencia del primer REM, siguiendo normas estrictas de la Sociedad Alemana de Electroencefalografía y Neurofisiología Clínica. Seleccionamos 19 pacientes y 2 controles sanos. Utilizamos el sueño espontáneo (con vigilia previa y deprivación de sueño) y el inducido con flunitrazepam, derivado diacepínico que no altera la latencia REM. La función EEG estuvo alterada, con importante disminución de latencia REM a cifras entre 10 y 35 minutos (valores normales = 80-90 minulos) en 16 pacientes, todos con diagnóstico de depresión larvada o enmascarada, con dificultades diagnósticas diferenciales marcadas. El parámetro REM no estuvo alterado en su latencia, en 3 pacientes y los 2 controles sanos. Ellos sufrían de depresiones reactivas o neuróticas, llamadas hoy presinápticas. La latencia REM tiene además importancia en la evaluación del tratamiento con antidepresivos tricíclicos. Por último correlacionamos nuestros hallazgos con los obtenidos por otros métodos, como los neuroquímicos y neuroendocrinológicos, en la depresión. Actualmente empleamos de rutina en la práctica privada y hospitalaria el parámetro REM del EEG, método de gran precisión, de uso fácil en nuestro medio, práctico y de bajo costo para el paciente, en relación a otros parámetros que aún nos están vedados por dichos motivos

Avances en el manejo psicofarmacologico del paciente narcoleptico / Advances in the psychopharmacological management of the narcoleptic patient

Se revisan algunos de los conceptos fundamentales de la biologia de la narcolepsia, con énfasis en los aspectos genéticos, neuroquímicos y psicofarmacológicos. Los autores dividen estos últimos en psicofármacos convencionales (antidepresivos y psicoestimulantes) y nuevos enfoques farmacológicos, (propranolol, mazindol, L-Dopa y gamahidroxibutirato), y comentan su experiencia preliminar con uno de ellos; la clonidina