Biomedical subjects

Wallace B Mendelson

Publications and source records attributed to Wallace B Mendelson.

9 recordsLinked to original sources

PubMed2005

Effect of sleep deprivation on righting reflex in the rat is partially reversed by administration of adenosine A1 and A2 receptor antagonists.

BACKGROUND: Similarities between naturally occurring sleep and general anesthesia suggest that the two states may interact physiologically. The authors have previously demonstrated that sleep deprivation potentiates anesthetic-induced loss of righting reflex (LORR) in rats. One possible mediator for this effect is adenosine, which accumulates in the brains of sleep-deprived animals and reduces anesthetic requirements. The authors tested in rats the hypothesis that potentiating effects of sleep deprivation on LORR can be altered by adenosine A1 and A2a receptor antagonists. METHODS: Five experiments were conducted. In each, rats underwent four trials, consisting of a 24-h period of either sleep deprivation or ad libitum activity followed by administration of a fixed dose of an adenosine antagonist or vehicle. Rats were then given isoflurane, and the time to LORR and recovery were measured. Each experiment tested a specific dose of an A1 receptor antagonist (8-cyclopentyltheophylline given via microinjection into the basal forebrain), an A2a receptor antagonist (ZM241385 via intraperitoneal administration), or both. In each experiment, all rats received all combinations of activity and drug/vehicle, separated by 5-7 days. RESULTS: In rested rats, neither antagonist altered the time to LORR. In sleep-deprived rats, both ZM241385 and 8-cyclopentyltheophylline prolonged the time to LORR and shortened recovery in a dose-dependent manner. Prolongation also occurred when subtherapeutic doses of both agents were coadministered. CONCLUSION: Both antagonists partially reversed the effect of sleep deprivation on anesthetic action. This result implies that deprivation-induced changes in adenosine receptor activity can alter LORR. Neither antagonist completely reversed this effect, suggesting possible non-adenosine-mediated effects of sleep deprivation.

Adenosine A1 Receptor Antagonists↗

PubMed2005

A review of the evidence for the efficacy and safety of trazodone in insomnia.

OBJECTIVE: Trazodone, a triazolopyridine antidepressant, is currently the second most commonly prescribed agent for the treatment of insomnia due to its sedating qualities. Given trazodone's widespread use, a careful review of the literature was conducted to assess its efficacy and side effects when given for treatment of insomnia. DATA SOURCES: In April 2003, a MEDLINE search was conducted using the search terms trazodone and insomnia and trazodone and sleep and restricted to 1980-2003, human subjects, and English language. As trazodone has been implicated in cardiac disorders, a further search was conducted using the term cardiac and trazodone. STUDY SELECTION: All clinical trials that measured any endpoint for insomnia efficacy were included in the assessment. A total of 18 studies were identified from the literature search. In addition, commonly used texts were consulted for information regarding adverse effects related to trazodone. DATA EXTRACTION: Because so few studies were identified by the literature search, all were evaluated and described. DATA SYNTHESIS: Evidence for the efficacy of trazodone in treating insomnia is very limited; most studies are small, conducted in populations of depressed patients, raise issues of design, and often lack objective efficacy measures. Side effects associated with trazodone are not inconsequential, with a high incidence of discontinuation due to side effects, such as sedation, dizziness, and psychomotor impairment, which raise particular concern regarding its use in the elderly. There is also some evidence of tolerance related to use of trazodone. CONCLUSION: Given the relative absence of efficacy data in patients with insomnia and the adverse events associated with trazodone's use in general, it is uncertain whether the risk/benefit ratio warrants trazodone's use in nondepressed patients with insomnia.

Adult↗

PubMed2004

Anesthesia and sleep.

Although both general anesthesia and naturally occurring sleep depress consciousness, distinct physiological differences exist between the two states. Recent lines of evidence have suggested that sleep and anesthesia may be more similar than previously realized. Localization studies of brain nuclei involved in sleep have indicated that such nuclei are important in anesthetic action. Additional observations that regional brain activity during anesthesia resembles that in the sleeping brain have raised the possibility that anesthesia may exert its effects by activating neuronal networks normally involved in sleep. In animals, behavioral interactions between sleep and anesthesia appear to support these mechanistic similarities. Rat studies demonstrate that sleep debt accrued during prolonged wakefulness dissipate during anesthesia. Moreover, anesthetic potency is subject both to circadian effects and to the degree of prior sleep deprivation. Such interactions may partly explain anesthetic variability among patients. Finally, sleep and anesthesia interact physiologically. Endogenous neuromodulators known to regulate sleep also alter anesthetic action, and anesthetics cause sleep with direct administration into brain nuclei known to regulate sleep. Together, these observations provide new research directions for understanding sleep regulation and generation, and suggest the possibility of new clinical therapies both for patients with sleep disturbances and for sleep deprived patients receiving anesthesia.

Anesthesia, General↗

PubMed2004

The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium.

This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.

Antidepressive Agents, Second-Generation↗

PubMed2004

Recovery from sleep deprivation occurs during propofol anesthesia.

BACKGROUND: Some neurophysiologic similarities between sleep and anesthesia suggest that an anesthetized state may reverse effects of sleep deprivation. The effect of anesthesia on sleep homeostasis, however, is unknown. To test the hypothesis that recovery from sleep deprivation occurs during anesthesia, the authors followed 24 h of sleep deprivation in the rat with a 6-h period of either ad libitum sleep or propofol anesthesia, and compared subsequent sleep characteristics. METHODS: With animal care committee approval, electroencephalographic/electromyographic electrodes and intrajugular cannulae were implanted in 32 rats. After a 7-day recovery and 24-h baseline electroencephalographic/electromyographic recording period, rats were sleep deprived for 24 h by the disk-over-water method. Rats then underwent 6 h of either propofol anesthesia (n = 16) or ad libitum sleep with intralipid administration (n = 16), followed by electroencephalographic/electromyographic monitoring for 72 h. RESULTS: In control rats, increases above baseline in non-rapid eye movement sleep, rapid eye movement sleep, and non-rapid eye movement delta power persisted for 12 h after 24 h of sleep deprivation. Recovery from sleep deprivation in anesthetized rats was similar in timing to that of controls. No delayed rebound effects were observed in either group for 72 h after deprivation. CONCLUSION: These data show that a recovery process similar to that occurring during naturally occurring sleep also takes place during anesthesia and suggest that sleep and anesthesia share common regulatory mechanisms. Such interactions between sleep and anesthesia may allow anesthesiologists to better understand a potentially important source of variability in anesthetic action and raise the possibility that anesthetics may facilitate sleep in environments where sleep deprivation is common.

Anesthesia Recovery Period↗

PubMed2004

The use of trazodone as a hypnotic: a critical review.

BACKGROUND: The last few years have seen a remarkable rise in the off-label use of trazodone for inducing sleep in nondepressed patients, to a degree that it is prescribed for this purpose as commonly as the leading hypnotic. In view of this widespread popularity, it seems prudent to review what is known of the safety and efficacy of trazodone when used in this context. DATA SOURCES AND SELECTION: A MEDLINE search of the literature published in English between 1975 and 2003 that included the keywords sleep, trazodone, Desyrel, depression, sleeping pill, and sedative-hypnotics was conducted. DATA SYNTHESIS: From this review, it is concluded that there are very few data to suggest that trazodone improves sleep in patients without mood disorder, though it does increase total sleep in patients with major depressive disorder. There are virtually no dose-response data for trazodone vis-à-vis sleep and, similarly, no available data on tolerance to its possible hypnotic effects. Areas of concern with its use include reports of significant dropout rates and induction of arrhythmias, primarily in patients with histories of cardiac disease, as well as the development of priapism. CONCLUSION: In summary, there are few data to support the use of trazodone in nondepressed subjects. When the risk-benefit ratio of trazodone is assessed, its side effect profile, which is much more significant than that of conventional hypnotics, should be considered.

Aged↗

PubMed2003

Baseline and post-deprivation recovery sleep in SCN-lesioned rats.

In humans, advancing age alters sleep patterns, reducing high voltage NREM sleep, sleep bout length, and delta power during NREM sleep. Although the mechanism by which these alterations occur is unknown, age-related changes in normal circadian processes may play a role. Increased age produces histological and functional changes in the suprachiasmatic nucleus (SCN), and alters the amplitude and phase of circadian rhythms. To examine the relationship between SCN function and age-related changes in sleep, we produced radiofrequency (RF) lesions of the SCN in rats of different ages and examined sleep behavior before and after sleep deprivation. Three-, 12- and 18-month-old rats received RF or sham lesions of the SCN. After verifying loss of circadian rhythm, 24-h EEG/EMG/temperature recordings were made in dim light before and after 24 h of sleep deprivation using the disk-over-water method. Age-related changes in NREM sleep, sleep bout length, and delta EEG power persisted despite SCN lesions. SCN lesions in all age groups increased baseline NREM sleep by 4% and NREM delta power by 15%, and decreased REM sleep by 10%. Although SCN lesions initially produced more REM and NREM sleep during recovery, 24-h values did not differ. Deteriorating SCN function is unlikely to cause the characteristic changes in sleep that occur with age. Our data also imply that an intact SCN slightly inhibits NREM sleep in the rat. Changes in NREM sleep and delta EEG power during recovery in lesioned rats suggest that the SCN may influence homeostatic regulation.

Age Factors↗

PubMed2002

Melatonin microinjection into the medial preoptic area increases sleep in the rat.

A wide variety of hypnotic compounds including triazolam, pentobarbital, ethanol and adenosine have been reported to enhance sleep when microinjected into the medial preoptic area (MPA) of the anterior hypothalamus of the rat. It is uncertain whether the pineal hormone melatonin, which may alter sleep/wake physiology in mammals, acts at this site. A previous report has indicated that a more widespread injection of melatonin into the hypothalamus of the cat induces sleep. In the present study we have examined the possibility that the MPA may mediate this effect. Nine adult rats were microinjected with melatonin 1 and 50 ug and vehicle into the MPA during the daytime in a repeated measures design study. It was found that melatonin increased total sleep time in a dose-dependent manner, primarily by increasing NREM sleep, and that wake time after sleep onset was significantly reduced. These data add melatonin to the growing list of compounds that increase total sleep after administration into the MPA, and suggest that the MPA may be a common site of action for such agents from a variety of pharmacologic classes. Based on previous studies, the possibility is raised that this sleep enhancement results from an alteration in function of the GABA(A)-benzodiazepine receptor complex.

Animals↗

PubMed2002

Sleep deprivation potentiates the onset and duration of loss of righting reflex induced by propofol and isoflurane.

BACKGROUND: Sleep and anesthesia differ physiologically but produce a similar loss of responsiveness to environmental stimuli. Recent data suggest that neuronal networks active in naturally occurring sleep also play a role in the anesthetized state. Changes in the propensity to sleep may then modify the response to anesthetic agents. The authors tested the hypothesis that sleep-deprived rats would require less anesthetic than rested rats to achieve a similar loss of responsiveness. METHODS: Rats were subjected to a 24-h period of either sleep deprivation or ad libitum activity. Sleep deprivation was produced by placing rats on a disk that rotated when sleep was detected by electroencephalographic and electromyographic (EEG, EMG) monitoring. A fixed dose of anesthetic agent was then administered, and the time required to induce loss of righting reflex was measured. Anesthetic administration was then stopped, and the time to recovery measured. All rats received both treatments separated by 7 days. RESULTS: Sleep deprivation reduced the time to loss of righting reflex by 40% for propofol (P < 0.025) and 55% for isoflurane (P < 0.025) and prolonged the time to recovery. In a separate control experiment, exposure to the deprivation environment but with disk rotation modified to allow adequate sleep did not affect the response to anesthetic administration. CONCLUSIONS: Sleep deprivation significantly potentiated the ability of inhaled and intravenous anesthetic agents to induce a loss of righting reflex. These results support the hypothesis that neuronal networks active in sleep are also involved in the anesthetized state and suggest that sleep deprivation may partly explain the variability in patient response to anesthesia.

Administration, Inhalation↗