Basic Research Literature Updates

Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery

Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. A prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries was carried out to determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications.

Characterization of Respiratory Compromise and the Potential Clinical Utility of Capnography in the Post-Anesthesia Care Unit: A Blinded Observational Trial

The utility of capnography to detect early respiratory compromise in surgical patients after anesthesia is unclear due to limited prospective data. The purpose of this trial was to determine the frequency and duration of capnography-detected respiratory adverse events in the post-anesthesia care unit (PACU). In this prospective observational trial, 250 consenting patients undergoing elective surgery with general anesthesia were monitored by standard monitoring together with blinded capnography and pulse oximetry monitoring. Capnography and the Integrated Pulmonary Index™ algorithm (IPI) detected respiratory adverse events earlier than standard monitoring in 75% and 88% of cases, respectively, with an average early warning time of 8 ± 11 min. Respiratory adverse events are frequent in the PACU, and the addition of capnography and IPI to current standard monitoring provides potentially clinically relevant information on respiratory status, including early warning of some respiratory adverse events.

Validation of an automated sleep spindle detection method for mouse electroencephalography.

Here we describe and validate an automated paradigm for rapid and reliable detection of spindles from mouse EEG recordings. This technique provides a powerful tool to facilitate investigations of the mechanisms of spindle generation, as well as spindle alterations evident in mouse models of neuropsychiatric disorders.

Identifying and validating blood mRNA biomarkers for acute and chronic insufficient sleep in humans: a machine learning approach.

Biomarkers for sleep debt status showed little overlap with previously identified biomarkers for circadian phase. Biomarkers for acute and chronic sleep loss also showed little overlap but were associated with common functions related to the cellular stress response, such as heat shock protein activity, the unfolded protein response, protein ubiquitination and endoplasmic reticulum-associated protein degradation, and apoptosis. This characteristic response of whole blood to sleep loss can further aid our understanding of how sleep insufficiencies negatively affect health. Further development of these novel biomarkers for research and clinical practice requires validation in other protocols and age groups.

Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes.

The delayed wound healing in obese, diabetic mice caused by SF is homologous to delayed wound healing in some patients with type 2 diabetes. The results support the interpretation that altered leptinergic signaling and inflammatory proteins contribute to delayed wound healing.

Optical probing of orexin/hypocretin receptor antagonists.

The present study investigated the function of Hypocretin (Hcrt or Orexin/OX) receptor antagonists in sleep modulation and memory function with optical methods in transgenic mice. The authors used Hcrt-IRES-Cre knock-in mice and AAV vectors expressing channelrhodopsin-2 (ChR2) to render Hcrt neurons sensitive to blue light stimulation.  Hcrt neurons were optogenetically stimulated and latencies to wakefulness were measured in the presence or absence of OX1/2R antagonists and Zolpidem.

Acute optogenetic stimulation of Hcrt neurons at different frequencies resulted in wakefulness. Treatment with dual OX1/2R antagonists (DORAs) DORA12 and MK6096, as well as selective OX2R antagonist MK1064 and Zolpidem, but not selective OX1R antagonist 1SORA1, significantly reduced the bout length of optogenetic stimulation-evoked wakefulness episode. DORAs and selective OX2R antagonists stabilize sleep and improve sleep-dependent cognitive processes even when challenged by optogenetic stimulation mimicking highly arousing stimuli.

Connectivity of sleep- and wake-promoting regions of the human hypothalamus observed during resting wakefulness

The findings of this study provide preliminary evidence relating a hypothalamic circuit investigated in animals to sleep–wake neuroimaging results in humans, with implications for our understanding of human sleep–wake regulation and the functional significance of anticorrelations.

Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity

Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). (…) We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.

Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats

Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction.

The results of this study  introduce kynurenine pathway metabolism and formation of metabolite kynurenic acid  as a novel molecular target contributing to sleep disruptions and cognitive impairments.